THE PCCA BLOG

The FDA Removes the Black Box Warning on Estrogen: What Pharmacists Need to Know (2025 Update)

Fri, 13 Feb 2026 16:24:46 GMT

On November 10, 2025, the U.S. Food and Drug Administration (FDA) announced a major update to menopausal hormone therapy labeling: the agency is removing the broad black box warning from estrogen-containing products used for menopause, with one important exception—systemic estrogen-alone products will retain the boxed warning for endometrial cancer risk in women with an intact uterus.¹

For pharmacists, this isn’t just a labeling change. It’s a clinical counseling opportunity to help patients understand who hormone replacement therapy (HRT) is appropriate for, when it is most beneficial, and which risks still require screening and monitoring.

How We Got Here: The Women’s Health Initiative (WHI) and the “HRT Fear” Era

The Women’s Health Initiative (WHI), launched in the 1990s and sponsored by the National Heart, Lung, and Blood Institute (NHLBI), enrolled more than 161,000 postmenopausal participants.² One key goal was to evaluate whether hormone therapy could prevent cardiovascular disease, fractures, and cancer.

Key WHI findings (as widely interpreted at the time):

Estrogen + progestin was associated with increased risk of coronary heart disease, stroke, venous thromboembolism (VTE), breast cancer, and dementia.
Estrogen alone (in women with prior hysterectomy) showed more favorable outcomes in younger subgroups and was associated with reduced coronary heart disease and all-cause mortality in some analyses. It also showed a statistically significant reduction in invasive breast cancer incidence overall.

The practical takeaway became blunt: HRT was seen as broadly dangerous, HRT prescribing dropped sharply, and many women stopped therapy or avoided it altogether.

What was often lost in translation: the average age in the WHI hormone trial was around 63—well beyond the typical menopause transition—and the regimen studied (oral conjugated equine estrogen plus medroxyprogesterone) does not represent the full range of current hormone therapy options. Risk estimates were frequently generalized to younger, newly menopausal patients, even though their benefit–risk profile can differ meaningfully.

What Exactly Is the FDA Changing in 2025?

In the November 2025 announcement, the FDA and HHS began removing broad boxed warnings that had linked systemic menopausal hormone therapy to cardiovascular disease, breast cancer, and probable dementia. The agencies explicitly described prior warnings as “misleading” when interpreted without clinical context and current evidence.¹

What remains: the FDA will retain the boxed warning for endometrial cancer on systemic estrogen-alone products, reinforcing the importance of appropriate progestogen use (or other uterine protection strategies) for patients with a uterus.

A centerpiece of the updated position is the FDA’s endorsement of the timing hypothesis: the benefit–risk balance of systemic HRT depends heavily on when therapy starts. The FDA cited randomized data suggesting that women who initiate systemic hormone therapy within 10 years of menopause onset or before age 60 may experience benefits such as fewer fractures and reduced all-cause mortality, along with favorable relative risk changes for certain cardiovascular outcomes.¹

What This Means for Pharmacists: Counseling That’s Accurate, Individualized, and Confidence-Building

For years, counseling often defaulted to: “Use the lowest dose for the shortest time—only if absolutely necessary.” The updated labeling supports a more nuanced approach.

As boxed warnings are removed, pharmacists play an even bigger role in helping patients understand why “estrogen” is not one uniform exposure.

And the “uterus rule” remains critical: unopposed systemic estrogen in a patient with an intact uterus increases risk of endometrial hyperplasia and endometrial cancer, and the boxed warning for this risk remains.¹

Age and timing now matter more in patient conversations
A healthy 52-year-old within a few years of her final menstrual period does not share the same baseline risk profile as a 68-year-old initiating hormone therapy for the first time. Pharmacists can help frame this distinction clearly and consistently.
Route, formulation, and regimen matter—and WHI isn’t the full story The WHI primarily studied a specific oral regimen. Today’s practice commonly involves:
- estradiol,
- micronized progesterone,
- lower doses, and
- individualized schedules.
Removing a black box warning is not the same as removing risk Pharmacists should still screen for contraindications and red flags—especially in patients with:
- history of estrogen-dependent cancer (including many breast cancers),
- active or high-risk VTE, known thrombophilia, or prior stroke,
- unexplained vaginal bleeding,
- severe liver disease,
- uncontrolled or significant cardiovascular disease (depending on route/regimen).
Expect fear, confusion, and skepticism—and be ready for it Many patients have internalized the message that “hormones cause cancer and heart attacks.” A helpful counseling approach:
- acknowledge why patients were warned for decades,
- explain what we’ve learned since WHI (especially the role of age, timing, and regimen),
- emphasize shared decision-making with the prescriber.

Bottom Line for Pharmacy Practice

The FDA’s removal of the broad black box warning on estrogen therapy for menopause is a course correction, not a claim that estrogen is risk-free.

For pharmacists, this moment means:

Updating how we explain HRT risk and benefit in plain language.
Shifting from “avoid at all costs” to patient-specific risk–benefit counseling.
Helping patients understand why labeling changed and how that supports informed decision-making.

Many women will spend a large portion of life in the postmenopausal phase, and symptom relief plus long-term health considerations are real quality-of-life issues. Pharmacists are uniquely positioned to translate this regulatory update into balanced, evidence-informed guidance.

References

U.S. Food and Drug Administration. HHS advances women’s health, removes misleading FDA warnings on hormone replacement therapy. FDA Newsroom. November 10, 2025. Accessed December 29, 2025. FDA Newsroom
National Heart, Lung, and Blood Institute. Women’s Health Initiative (WHI). NHLBI, National Institutes of Health. Accessed December 29, 2025. NHLBI WHI

Illuminating Stealth Syndromes

Wed, 29 Jan 2025 17:08:00 GMT

A forthcoming documentary from the LDN Research Trust gives compounding pharmacists, physicians and prescribers an opportunity to learn about a group of complex and debilitating syndromes that affect one in six Americans — syndromes that occur in almost every part of the body, often accompany each other and collectively exacerbate the patient’s pain and other symptoms. This article briefly summarizes these syndromes and their overlapping symptoms and discusses how you can help educate providers in your community — as well as your staff and patients — about their effects, along with the potential use of low-dose naltrexone (LDN) in compounding preparations.

Summary of Syndromes

Stealth syndromes include mast cell activation syndrome (MCAS), postural orthostatic tachycardia syndrome (POTS) and Ehlers-Danlos syndrome (EDS), each of which is discussed below.

MCAS (Mast Cell Activation Syndrome)

Found in most organs of the body, mast cells are part of the immune system and are responsible for immediate allergic reactions that are triggered by allergic substances such as medications, infections, chemicals and insect bites. Mediators stored in or created by mast cells are released and create allergic reactions. A trigger from an allergen is called activation and the release of mediators is called degranulation.

MCAS is caused by dysfunction of mast cells; patients afflicted by MCAS experience repeated episodes of allergic reactions with accompanying symptoms:

Fatigue, headache, tingling, chills
Rapid pulse (tachycardia), low blood pressure (hypotension) and fainting
Itching (pruritus), hives (urticaria), swelling (angioedema) and skin flushing
Wheezing, shortness of breath and harsh noise when breathing (stridor) due to throat swelling
Diarrhea, nausea with vomiting and cramping abdominal pain^1,2

POTS (Postural Orthostatic Tachycardia Syndrome)

POTS (also referred to as dysautonomia) is caused by a malfunction in part of the autonomic nervous system, which controls involuntary body functions such as breathing and heart rate. The syndrome is considered one of a group of disorders that present symptoms of orthostatic intolerance (OI). OI is a condition where an excessively reduced volume of blood returns to the heart after an individual stands up after laying down.

Patients afflicted with POTS often experience:

Lightheadedness or fainting when standing
A rapid increase in heartbeat (more than 30 beats per minute or exceeds 120 beats per minute)
Low blood pressure
Digestive and bladder problems
Temperature and sweating dysregulation
The syndrome often prevents individuals from exercising due to onset of fainting spells or dizziness. POTS is often associated with EDS.³

EDS (Ehlers-Danlos Syndrome)

EDS is a group of disorders that affect connective tissues that support the skin, tendons, ligaments, bone, blood vessels and many organs and tissues. An unusually large range of joint movement (hypermobility) occurs in most forms and is the hallmark feature of the hypermobile type.

Patients afflicted with hypermobile EDS (hEDS) may present some or all of the following symptoms:

Joint hypermobility
Loose, unstable joints that easily dislocate
Joint pain and clicking joints
Extreme fatigue
Skin that bruises easily
Digestive problems, such as heartburn and constipation
Dizziness and an increased heart rate after standing up
Problems with internal organs, such as mitral value issues or organ prolapse (types include bladder, pelvic and rectal prolapse)
Urinary incontinence (bladder control)⁴

Compassion and Concern: The LDN Research Trust

Linda Elsegood, Chief Executive Officer and founder of the LDN Research Trust, refers to the collection of MCAS, POTS and EDS as “Stealth Syndromes.” Keenly aware of the debilitating impacts and empathetic for patients who suffer from these syndromes, Linda shared her concerns during The Mortar & Pestle podcast. “Patients with MCAS are also susceptible to having EDS and POTS; they tend to go hand-in-hand,” Linda said. “Some of these patients come into the doctor’s office with 40 different symptoms and practitioners have no idea where to start. Some physicians just throw up their hands and walk away. Others just treat one or two individual issues. But until you get down to the root cause — it’s nothing more than a Band-Aid.”

Adding insult to injury, many conventionally prescribed tests return with negative results, which add to the growing pile of doubts among family and friends.

“A lot of the tests, they do come back negative, which leads family and friends to thinking, ‘Well, if the doctors can't find anything wrong with you, there is nothing really wrong with you!’” Linda said. “I know one lady whose parents wouldn't talk to her anymore because they thought she was just a hypochondriac, that there was nothing really wrong with her. And that is so isolating for the patient.” Although considered a rare disease, Dr. Leonard Weinstock, a gastroenterologist and leading expert on MCAS, estimates one-in-six people are afflicted with the syndrome in the Northern Hemisphere; most are unaware.

During the podcast, Linda likened the lack of awareness to Lyme disease. “There were no reported cases of Lyme disease anywhere in the United States because there was no true diagnosis. And so they couldn't gather the data. And then very quickly, they said Lyme disease existed in the United States.”

Help Spread Awareness

Linda is calling on compounding pharmacists — notably PCCA members — to raise awareness of Stealth Syndromes and the potential use of low-dose naltrexone (LDN) in preparations.

The LDN Research Trust developed a documentary, “Understanding Stealth Syndromes,” that sheds light on these esoteric conditions. The documentary, which airs for 24 hours on February 27 (to accommodate global time zones), explains the underlying root causes, why most doctors miss these conditions, potential treatments and more.

Compounding pharmacies are urged to help raise awareness by:

Purchasing a documentary license — $100 for up to 50 individuals
Hosting an event at their pharmacy or a local venue
Inviting community physicians, prescribers and patients to view the documentary

“We’re aiming to raise awareness and connect individuals suffering from undiagnosed Stealth Syndromes with knowledgeable local providers,” Linda said. “Compounding pharmacists, technicians and staff are compassionate — many are aware of the benefits of LDN — and are adept at providing personalized preparations to these patients.

“They are positioned to develop awareness in their communities and can purchase as many licenses to the documentary as needed. Once we have sold the license, they can do whatever they like.”

This includes selling tickets to and/or publicizing the event on their respective pharmacy websites.

“We are happy to help them publicize or advertise the event,” Linda said. “On our website and throughout our social media platforms, we list all pharmacies who purchased licenses for the documentary, as well as their locations, so people know who to contact to attend viewings. We also hope to invite local media to these events; if an event is sold out, many become really interested and will send reporters who will broadcast or write about it.”

Watch the compelling trailer for “Understanding Stealth Syndromes”. Click Here.

To purchase one or more licenses for the documentary, Click Here.

For additional information, email contact@ldnresearchtrust.org.

Listen as Linda shares her personal struggles and the impetus for creating the LDN Research Trust, as well as the need for public awareness of Stealth Syndromes, in The Mortar & Pestle Podcast.

PCCA is recognized as the leader of quality products, education and advocacy in the compounding industry. Find out how a PCCA membership can benefit your compounding practice.

References

American Academy of Allergy, Asthma & Immunology. Mast Cell Activation Syndrome (MCAS). August 2024. Accessed January 2025 at https://www.aaaai.org/conditions-treatments/related-conditions/mcas#:~:text=Idiopathic%20Mast%20Cell%20Activation%20Syndrome,are%20released%20during%20those%20episodes
POTS UK. Mast Cell Activation Syndrome. Version 3. Last reviewed July 2024. Accessed January 2025 at https://www.potsuk.org/about-pots/associated-conditions/mcas/
National Institute of Neurological Disorders and Stroke. Postural Tachycardia Syndrome (POTS). Last reviewed July 2024. Accessed January 2025 at https://www.ninds.nih.gov/health-information/disorders/postural-tachycardia-syndrome-pots
National Health Service UK. Ehlers-Danlos Syndromes. Last reviewed October 2022. Accessed January 2025 at https://www.nhs.uk/conditions/ehlers-danlos-syndromes/#:~:text=types%20of%20EDS-,Hypermobile%20EDS,with%20bladder%20control%20(urinary%20incontinence)

These statements are provided for educational purposes only. They have not been evaluated by the Food and Drug Administration, and are not to be interpreted as a promise, guarantee or claim of therapeutic efficacy or safety. The information contained herein is not intended to replace or substitute for conventional medical care or encourage its abandonment.

Bacterial Vaginosis: A Persistent Challenge

Thu, 16 Jan 2025 16:42:55 GMT

by Deborah H. Clark, RPh, FACVP, PCCA Clinical Compounding Pharmacist

Bacterial vaginosis (BV) is the most common vaginal infection that affects women around the globe. In addition to its effects on total health, BV can significantly impact reproductive wellness. The condition is thought to originate from a decrease of Lactobacilli in the vagina, resulting in an imbalance in the natural vaginal microbiome.¹ In the following article, we explore the pathogens associated with BV and challenges with commercial treatments, as well as compounding options and an innovative base that may potentially improve patient compliance.

Common and Uncommon Pathogens

One of the more common pathogens associated with BV is Gardnerella; however, other pathogens can be present. According to researchers, many studies have demonstrated the relation of Gardnerella vaginalis with other bacteria in causing BV, such as Lactobacillus, Prevotella and anaerobes. In addition, patients with BV may be infected with Mobiluncus, Bacteroides, Peptostreptococcus, Fusobacterium, Veillonella, Eubacterium, Mycoplasma hominis, Ureaplasma urealyticum, Streptococcus viridans and Atopobium vaginae. In many cases, the infecting pathogen will form a biofilm that makes the infection persistent and treatment challenging.²

Diagnosis and Compounding Options

Most patients present with a complaint of a malodorous discharge; a diagnosis of BV is then made through physical exam and testing. In some cases, physicians will treat empirically, using commercially available antibiotic vaginal suppositories, gels or creams. Clindamycin and metronidazole are two agents that are commonly selected and administered in these patients. When these agents fail to resolve the infection, many practitioners will consult a compounding pharmacist to discuss test results; the compounding pharmacist may then suggest more culture and sensitivity testing for specific bacterial strains.

Additional culture and sensitivity testing will confirm what organisms are present to employ a more targeted approach when choosing active pharmaceutical ingredients (APIs). As stated earlier, a biofilm is normally present, so the addition of a biofilm disrupting agent, such as edetate disodium in a 0.5% concentration, would be a smart addition to the formulation.³

Ellage^® Anhydrous Vaginal: The Base of Choice

Using the right base vehicle is important when compounding preparations for BV patients. Ellage Anhydrous Vaginal is an excellent option due to its consistent delivery of APIs and potential improvement of compliance.

Ellage contains a self-emulsifying drug delivery system that creates a microemulsion when it contacts vaginal fluid. This emulsion releases APIs from the base into the mucosa. Once the APIs are released, the emulsification system holds the APIs to the surface, prolonging contact time. The combination of excellent release properties and prolonged contact time helps facilitate the action of the antimicrobials used in treating BV patients.

Leakage is a common complaint from patients using vaginal preparations and may affect compliance. In vitro testing (PCCA Document #99816) showed Ellage is likely to adhere to vaginal tissue for a long period of time without leakage or messiness, despite vaginal secretions. In vitro testing (PCCA Documents #99817 and #99818) also showed safety with minimal irritation on the vaginal mucosal tissue and no effect on vaginal pH (PCCA Document #99815). Ellage is an anhydrous vehicle, offering the option of longer beyond-use dates (BUDs*).

Commonly requested formulas for patients with BV include PCCA Formula #13836, PCCA Formula #13858, PCCA Formula #14396 and PCCA Formula #14584.

PCCA members with clinical services access may view and/or download PCCA Ellage formulations — including formulas with FormulaPlus™ BUD and stability studies — after logging on to our Members-Only Website. Clinical services access also allows members to contact our Clinical Services team for additional information on compounding Ellage preparations for patients with BV and other compounding concerns.

*USP 795 establishes BUD limits by type of preparation in the absence of a USP−NF Compounded Preparation Monograph or CNSP-specific stability information.

PCCA is recognized as the leader of quality products, education and advocacy in the compounding industry. Find out how a PCCA membership can benefit your compounding practice.

References

Kairys N, Carlson K, Garg M. Bacterial Vaginosis. [Updated 2024 May 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Accessed December 2024at https://www.ncbi.nlm.nih.gov/books/NBK459216/
Girerd P and Riven M, Price TM, et al. Bacterial Vaginosis. Medscape > Drugs & Diseases > Obstetrics & Gynecology. Accessed December 2024 at https://emedicine.medscape.com/article/254342-overview
Finnegan S, Percival SL. EDTA: An Antimicrobial and Antibiofilm Agent for Use in Wound Care. Adv Wound Care (New Rochelle). 2015 Jul 1;4(7):415-421. Accessed December 2024 at https://pubmed.ncbi.nlm.nih.gov/26155384

Easing Drug & Disease Side Effects in Hospice Patients

Fri, 03 Jan 2025 00:30:22 GMT

by Sam Hamburger, PharmD Candidate, PCCA Clinical Services Intern, and Beau Harger, PharmD, PCCA Clinical Compounding Pharmacist/Training Instructor

The fundamental purpose of hospice is to help patients retain comfort, dignity and quality of life as they approach the end of life. During this stage, nausea and vomiting — either caused by medication side effects or from symptoms of a disease — are common. These and other side effects may lead to unnecessary stress and patient discomfort.¹ In the following article, we review a commonly used topical gel that lessens nausea and vomiting,² as well as the PCCA base vehicle that may enhance penetration of active pharmaceutical ingredients (APIs).

ABH Gel: Common & Customized

ABH gel is often used to help patients with nausea, vomiting and delirium during hospice and palliative care. The gel’s name comes from the API brands that are used in it — lorazepam (Ativan^®), diphenhydramine (Benadryl^®) and haloperidol (Haldol^®).

Lorazepam is a short-acting benzodiazepine used in patients with anxiety, shortness of breath and nausea. It acts on postsynaptic GABA receptors — a type of receptor in the brain that responds to the neurotransmitter gamma-aminobutyric acid (GABA) — located in multiple sites within the central nervous system (CNS). Sedation and confusion are common side effects.

Diphenhydramine is a first-generation antihistamine that acts on the histamine-1 (H-1) receptor. It is used for sedation, nausea and the extrapyramidal effects — the involuntary movement disorders such as tardive dyskinesia — of dopamine antagonists. Considered an anticholinergic medication, it causes a variety of side effects, including drowsiness, constipation, confusion, dry mouth, agitation, anxiety and urinary retention.

Haloperidol is a first-generation antipsychotic that acts primarily by inhibiting the D2 dopaminergic receptor — a protein that plays a key role in many brain functions. The API is used to sedate and calm patients. It carries an increased risk of extrapyramidal side effects, and oral haloperidol has a higher risk of delirium and mortality in palliative care patients.³

As a topical application, ABH gel is typically administered on the wrist, rubbed behind the ears or on the bottom of the feet.

Since ABH gel is not commercially available, compounding pharmacies may compound ABH preparations tailored to meet the unique needs of individual patients. The formulation should use a base vehicle that is smooth to the touch and that delivers exceptional API permeation through various levels of the skin.

Studied Results: PermE8^® Anhydrous Gel

PermE8 Anhydrous Gel ticks all of these boxes. Not only does it feature a silky texture that spreads quickly compared to other topical preparations, but it also can hold multiple APIs — including salt forms — in one compounded preparation. And due to water activity (Aw) of less than 0.6 (<.6), PermE8 offers the potential for longer beyond-use dates (BUDs).* Extended BUDs benefit not only compounding pharmacies by helping to lower operating costs but also hospice providers and caretakers due to fewer pharmacy refills.⁴

The need to deliver exceptional API permeation through various levels of the skin was supported in an independent study that compared the percutaneous absorption of ketoprofen in a formulation using PermE8 Anhydrous Gel to a formulation using PCCA Lipoderm®. Results indicated no significant difference between the two formulations (see Figure 1). Researchers concluded that the extent and rate of absorption in the PermE8 formulation is comparable to the industry-leading, permeation-enhancing Lipoderm.⁴

Figure 1
Across donor summary: the mean percutaneous absorption and distribution of ketoprofen in two compounded formulas after 48 hours diffusion.

PCCA members with clinical services access may view and/or download PCCA formulations to compound ABH gel preparations after logging on to our Members-Only Website. Clinical services access also allows members to contact our Clinical Services team for additional information on compounding ABH gel, hospice and palliative care or other compounding concerns.

PCCA is recognized as the leader of quality products, education and advocacy in the compounding industry. Find out how a PCCA membership can benefit your compounding practice.

*USP 795 establishes BUD limits by type of preparation in the absence of a USP−NF Compounded Preparation Monograph or CNSP-specific stability information.

References

Blaszczyk AT, Bailey TA, Tapia S. ABH Gel: Comforting Cure or Pricey Placebo?. J Am Med Dir Assoc. 2021;22(1):23-27. Accessed December 2024 at https://pubmed.ncbi.nlm.nih.gov/33246839/
Moon RB. ABHR Gel in the Treatment of Nausea and Vomiting in the Hospice Patient. Int J Pharm Compd. 2006;10(2):95-98. Abstract accessed December 2024 at https://pubmed.ncbi.nlm.nih.gov/23974181/
Dahal A, Neupane R, Boddu SH, et al. Percutaneous Absorption of Lorazepam, Diphenhydramine Hydrochloride, and Haloperidol from ABH Gel. Int J Pharm Compd. 2020;24(2):168-175. Abstract accessed December 2024 at https://pubmed.ncbi.nlm.nih.gov/32196480/
PCCA Science. PCCA PermE8™ Anhydrous Ge Product Information Sheet. Document number 99608; 2018. Accessed December 2024 at PCCA Members-Only Website
PCCA Science. (2018) PermE8/Lipoderm Technical Report: Evaluation of the in vitro Human Skin Percutaneous Absorption of Ketoprofen in PCCA PermE8 Anhydrous Gel vs. PCCA Lipoderm . Document number 99732. Accessed December 2024 at PCCA Members-Only Website.

Balance Hormones and Grow Your Practice

Thu, 19 Dec 2024 23:31:00 GMT

The numbers are in — forecasters predict 1.1 billion women worldwide will experience menopause in 2025.¹ In the U.S., more than 1 million women reach menopause each year, and more than 75 percent of these women work during menopause transition years. Research conducted by the National Institute on Aging indicates menopausal hormone therapy (MHT) reduced the severity of menopause symptoms while elevating mood, sexual function, cardiovascular and brain health.²

With all of these studies and reports, it’s no wonder that hormone replacement therapy (HRT) currently leads all compounding therapeutic areas in the U.S. — or that the U.S. HRT market value is forecasted to reach $12.6 billion within the next five years.³Maintaining up-to-date HRT knowledge is now a top priority for compounding pharmacists who support patients that experience the many side effects of perimenopause or menopause.

Introducing PCCA Master Courses: HRT

PCCA Master Courses: Hormone Replacement Therapy (HRT), a new education tool, will prepare compounding pharmacists to meet the needs of this expanding female patient segment. The dynamic platform delivers specialty education using:

Online, self-paced HRT education available on demand
Engaging, multimedia formats for interactive learning
Continuing education (CE) courses with 25 hours of CE applied for

“We understand the many nuances of compounding and recognize the varied responsibilities of compounding pharmacy owners and pharmacists,” said PCCA Director of Online Education Jerra Banwarth, RPh, FAPC. “This is why we wanted to develop a flexible program that accommodates their busy schedules. We also wanted to make it a dynamic experience to captivate and retain their interest — regardless of time or day. And we recognize the importance of specialty education — it’s an advantage that a compounding pharmacist can use to distinguish their practice from competitors.”

PCCA Master Courses: HRT was developed to be easy to follow and provides a true multimedia experience. Education is delivered through impactful audio, visual and animations, which helps learners better understand the physiological concepts of perimenopause through post-menopause.

Master Courses: HRT is composed of five courses:

Introduction to Hormones
Reviews foundational anatomy and physiology; explores the goals of HRT.
Testing and Therapy Options
Takes an in-depth look at different testing options and applications for utilization.
Clinical Evidence for HRT Patient-Centered Care
Provides insights into patient specific therapies, including dosing, routes of administration and formulations.
Bases for HRT Application
Explores appropriate bases, devices and compounding considerations for HRT formulations.
Building a Thriving HRT Compounding Practice
Provides a foundation for marketing your expertise and knowledge; offers professional recommendations on how to implement a hormone consultation practice.

Earn Your Certified Master Designation in HRT

Upon successfully completing the Master Course, learners can take their expertise further with the PCCA Certified Master* designation. The designation is achieved in two steps:

Successfully complete all courses in PCCA Master Courses: HRT by February 7, 2025.
Attend a PCCA HRT Symposium within 12 months: in-person or virtually at the Las Vegas HRT Symposium, February 20-22, or at the virtual HRT Symposium on July 24-25, 2025.

The HRT Symposium and Master Courses: HRT are complimentary educational achievements designed to help shorten the learning curve and create a powerful experience for pharmacists. In addition to increasing their knowledge, those who achieve the PCCA Certified Master designation can use it to market their practice to prescribers and patients.

“We work to ensure our education programs and symposiums benefit all attendees — from pharmacists to pharmacy technicians and medical practitioners,” said PCCA Senior Director of Education Renee Prescott. “We hire industry-expert speakers who share cutting-edge clinical research, provide ample time for participants to network and we apply for CEs, yet another benefit. More than 98 percent of participants give us an ‘A’ grade.”

Participants who achieve their initial Certified Master designation have the option to recertify by attending the PCCA HRT Symposium every two years.

“There’s always something new to learn,” said Jerra. “Serving this population not only helps women, it also benefits their families, friends, workplace and communities.”

Prepare to meet the needs of a growing market. Register today for PCCA Master Courses: HRT.

PCCA members with clinical service access may contact our Clinical Services team for additional information on compounding for HRT and other compounding concerns.

PCCA is recognized as the leader of quality products, education and advocacy in the compounding industry. Find out how a PCCA membership can benefit your compounding practice.

*The Certified Master award is an internal designation provided by PCCA. It does not denote a board certification or certification by a licensed health care body. Pharmacists and practitioners are eligible for the Certified Master designation.

References

Zhang L, Ruan X, Cui Y, Gu M, Mueck AO. Menopausal Symptoms and Associated Social and Environmental Factors in Midlife Chinese Women. Clin Interv Aging. 2020;15:2195-2208. Published 2020 Nov 16. doi:10.2147/CIA.S278976
National Institute on Aging. News. Research explores the impact of menopause on women’s health and aging. Research Highlights. 2022. Accessed December 2024 at https://www.nia.nih.gov/news/research-explores-impact-menopause-womens-health-and-aging#hormone
Grand View Research. Hormone Replacement Therapy Market Size, Share & Trend Analysis By Product (Estrogen & Progesterone Replacement Therapy), By Route of Administration, By Disease Type, By Region, And Segment Forecasts, 2023 – 2030. Accessed October 2024 at https://www.grandviewresearch.com/industry-analysis/hormone-replacement-therapy-market

Microdosing GLP-1 RAs: Fad or Forever?

Fri, 22 Nov 2024 15:58:06 GMT

by Jennifer Lines, PharmD Candidate, PCCA Clinical Services Intern, and Catherine Henderson, PharmD, PCCA Clinical Compounding Pharmacist

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have revolutionized metabolic health and weight management, leading to a host of new weight loss wonder drugs. But did you know that recent evidence shows these new drugs may do more than just help with weight loss and diabetes? And at a fraction of the standard dose?

Looking Back on GLP-1 RAs

Originally discovered in the saliva of the Gila monster, exenatide — a GLP-1 RA— was approved as a twice-daily injection by the FDA in 2005 for adults with type 2 diabetes.¹ Within the past decade, longer-acting GLP-1 RA formulations entered the market as once-weekly, self-administered injectable pens — most notably, semaglutide.

Recent FDA approvals and indications for products containing semaglutide include the reduction of cardiovascular risk in patients with type 2 diabetes and body weight reduction for obesity. New research, however, reveals the potential for additional benefits of the drugs.

Potential Benefits of GLP-1 RAs

Known for their metabolic benefits, emerging studies suggest GLP-1 RAs may help improve kidney function, cardiovascular health, non-alcoholic fatty liver disease, Alzheimer's disease and Parkinson’s disease.²

GLP-1 RAs, such as semaglutide, also show potential anti-inflammatory properties. Although the specific mechanisms are not understood, reports indicate that semaglutide can modulate inflammatory processes by reducing levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and high-sensitivity C-reactive protein (hsCRP).

In an animal model, semaglutide demonstrated neuroprotective effects and improved cognitive function by inhibiting the release of inflammatory cytokines mediated by the NLRP3 inflammasome, a protein involved in regulating the innate immune system and inflammatory responses.

GLP-1 receptors are also found on different immune cells, such as neutrophils and eosinophils, and their activation has modulatory effects on immune responses and inflammatory processes associated with these types of cells.³

What Is Microdosing?

Microdosing is not an official medical term; it refers to taking less than the standard dose of a medication to achieve benefits while potentially minimizing undesirable side effects.

The term microdosing has risen in popularity in recent years. Initially, it referred to taking small doses of psychedelic drugs to alleviate symptoms of depression and anxiety, or boost mood and creativity. Interest in microdosing GLP-1 RAs is growing among many holistic physicians.⁴

Endogenous GLP-1 vs. Exogenous GLP-1 RAs

At normal physiological levels, active GLP-1 levels peak around 30-60 minutes after ingesting a meal before being rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4). During DPP-4 inhibition, levels of active GLP-1 increase up to 2-3 times. However, with exogenous GLP-1 RAs, active levels of GLP-1 RAs can rise to 10-30 times the normal physiological levels (depending on the agent used) and maintain steadily high levels independent of meal ingestion. One of the most common reasons patients discontinue GLP-1 RA treatment is due to gastrointestinal side effects, which could be attributed to the markedly high GLP-1 RA levels.⁵

Microdosing GLP-1 RAs

Anecdotal discussions between holistic practitioners suggest microdosing semaglutide may help people lose weight while limiting side effects. Naturopathic physician Dr. Tyna Moore, for example, suggests people with reduced GLP-1 levels may benefit from lower dosing and slowly increasing to the patient’s normal physiological levels. Dr. Moore also believes that slower, more sustainable weight loss allows the body more time to adjust to changes in weight, reducing the side-effect profile and potentially leading to better long-term success.⁶

While there are no clinical studies exploring the concept of microdosing GLP-1 RAs, it may be a useful tool for a holistic metabolic health strategy. It is important to remember that GLP-1 RAs are only one piece of the puzzle and should always be recommended in conjunction with diet, exercise and lifestyle modifications.

Smaller doses of GLP-1 RAs may not benefit those with severe metabolic dysfunction or those needing substantial weight loss. However, it may be helpful to those seeking a more gradual approach to weight loss while potentially providing overall health benefits like anti-inflammatory and neuroprotective effects.

While the safety of GLP-1 RAs is well established, current scientific evidence on the efficacy of microdosing GLP-1 RAs is lacking and further research is required to assess its benefits at lower doses.⁷

PCCA members with clinical services access may contact our Clinical Services team for help with microdosing GLP-1 RAs and other compounding concerns.

References

Paternoster S, Falasca M. Dissecting the Physiology and Pathophysiology of Glucagon-Like Peptide-1. Front Endocrinol (Lausanne). 2018;9:584. Published 2018 Oct 11. doi:10.3389/fendo.2018.00584
Laurindo LF, Barbalho SM, Guiguer EL, et al. GLP-1a: Going beyond Traditional Use. Int J Mol Sci. 2022;23(2):739. Published 2022 Jan 10. doi:10.3390/ijms23020739
Yaribeygi H, Maleki M, Jamialahmadi T, et al. Anti-inflammatory benefits of semaglutide: State of the art. J Clin Transl Endocrinol. 2024;36:100340. Published 2024 Mar 28. doi:10.1016/j.jcte.2024.100340
Mammoser G. (fact checked by Seladi-Shulman J.) Ozempic Microdosing Is Gaining Popularity. Does It Work for Weight Loss? Healthline. Published 2024 Oct 17. https://www.healthline.com/health-news/ozempic-microdosing-weight-loss
Smits MM, Holst JJ. Endogenous glucagon-like peptide (GLP)-1 as alternative for GLP-1 receptor agonists: Could this work and how?. Diabetes Metab Res Rev. 2023;39(8):e3699. doi:10.1002/dmrr.3699
Fitzgerald, J. (Host). (2023, October 12). Is Ozempic a miracle medicine? Heal Thy Self w/ Dr. G #283 [Video]. YouTube. https://www.youtube.com/watch?v=xI37HDVEMjo
Smits MM, Van Raalte DH. Safety of Semaglutide [published correction appears in Front Endocrinol (Lausanne). 2021 Nov 10;12:786732. doi: 10.3389/fendo.2021.786732]. Front Endocrinol (Lausanne). 2021;12:645563. Published 2021 Jul 7. doi:10.3389/fendo.2021.645563

A Personalized Approach to HRT for Perimenopausal Women

Thu, 14 Nov 2024 04:23:17 GMT

by Sara Hover, RPh, FAARM, PCCA Director of Clinical Services

Perimenopause is a unique phase in a woman’s life, marked by fluctuating hormones and a wide range of symptoms. Hormone replacement therapy (HRT) can offer relief, but a one-size-fits-all approach may not yield the best results. A personalized approach, tailored to each woman’s unique hormonal profile, lifestyle and symptoms, can make all the difference in managing this transition effectively. Let’s explore the factors that contribute to low estrogen, the role of cortisol and progesterone, and why a customized approach to HRT is essential for perimenopausal women.¹

Understanding Estrogen Levels in Perimenopause

Estrogen is a key hormone for various bodily functions, from reproductive health to mood regulation. During perimenopause, estrogen levels fluctuate and eventually decline when menopause is reached. Several factors can contribute to low estrogen levels during perimenopause.

First, the natural abatement of ovarian function plays a major role; as women approach menopause, ovarian follicles reduce in number and function, resulting in decreased estrogen production. Genetic predisposition can also influence estrogen levels, as some women have genetic factors that may lead to an earlier or more abrupt drop. Additionally, lifestyle factors, including diet, stress and physical activity levels, significantly impact estrogen. For instance, poor nutrition or extreme physical training can suppress estrogen production.² Another crucial factor is high cortisol levels. Chronic stress increases cortisol, which may inhibit the body’s ability to produce adequate estrogen.³

By identifying these factors, healthcare providers can develop a more precise treatment plan, addressing not only hormonal imbalances but also lifestyle factors that might be exacerbating symptoms. During perimenopause, women are still making estrogen — maybe in an erratic fashion — but identifying the cause of low estrogen is most important. We should not give estrogen until there is certainty that the patient has entered menopause. Keep in mind that the testing results are a one-time snapshot of that moment and results may vary over time.¹

The Role of Cortisol in Perimenopausal Health

Cortisol, often referred to as the “stress hormone,” is produced by the adrenal glands and plays a significant role in managing stress and regulating metabolism. For perimenopausal women, high cortisol levels can have several consequences. Elevated cortisol can lead to increased fatigue and mood swings, as it causes feelings of exhaustion, irritability and mood fluctuations. It also disrupts other hormones; high cortisol can hinder estrogen production, exacerbating symptoms like hot flashes, insomnia and night sweats.

Furthermore, cortisol impacts progesterone levels due to a phenomenon known as “pregnenolone steal.” Since cortisol production draws on the same hormonal precursor (pregnenolone) that produces progesterone, the body under stress prioritizes cortisol production over progesterone, potentially leading to imbalances.⁴ By managing cortisol levels through stress reduction techniques, exercise and lifestyle modifications, women can help balance their hormones and reduce the intensity of perimenopausal symptoms.

Progesterone: The Balancing Hormone

Progesterone plays a vital role in regulating estrogen, stabilizing mood, promoting restful sleep and reducing anxiety. During perimenopause, progesterone levels begin to decline as ovulation becomes irregular, leading to several potential challenges.

One significant issue is estrogen dominance; when progesterone is low, estrogen may dominate, resulting in symptoms such as weight gain, bloating, breast tenderness and mood swings. Progesterone also affects sleep and anxiety levels, as it has a calming effect on the brain. Low levels of progesterone may lead to sleep disturbances and heightened anxiety, making this transitional phase more challenging.⁵ In addition, progesterone supports bone health, so declining levels can impact bone density over time.⁶ Replenishing progesterone through bioidentical hormones or other supplements, as determined by a healthcare provider, can help mitigate these symptoms and maintain hormonal balance.

Benefits of a Personalized HRT Approach

A personalized HRT approach considers each woman’s unique hormonal profile, lifestyle factors and symptom severity. This approach offers several distinct advantages. First, targeted hormone support is possible by measuring hormone levels and monitoring symptoms, allowing health care providers to recommend specific combinations and dosages of estrogen, progesterone and other hormones based on individual needs.

Personalized HRT plans address underlying causes; beyond hormone therapy, they may include lifestyle and nutritional adjustments to address root causes such as high cortisol or low progesterone. Ultimately, a personalized approach enhances a woman’s quality of life by addressing a broad range of factors — from hormonal imbalances to lifestyle changes — so she can experience a smoother perimenopausal transition with improved energy, mood and sleep quality.

Perimenopause doesn’t have to be a time of discomfort and uncertainty. A personalized approach to HRT empowers women to navigate this transition with a clear, effective and safe plan. With proper guidance, perimenopausal women can regain control over their bodies, ensuring that their unique needs are met. Whether through bioidentical hormone therapy, lifestyle changes or stress management, each woman deserves an individualized strategy that supports her well-being through this important life stage.

PCCA members with clinical services access may contact our Clinical Services team to answer any questions about HRT and other compounding concerns.

References

Smith, P., What You Must Know About Women’s Hormones. 2nd. Ed. Garden City Park, NY: Square One Publishing, 2022.
Delamater L, Santoro N. Management of the Perimenopause. Clin Obstet Gynecol. 2018 Sep;61(3):419-432. doi: 10.1097/GRF.0000000000000389. Accessed 2024 at https://pubmed.ncbi.nlm.nih.gov/29952797/
Woods NF, Mitchell ES, Smith-Dijulio K. Cortisol levels during the menopausal transition and early postmenopause: observations from the Seattle Midlife Women's Health Study. Menopause. 2009 Jul-Aug;16(4):708-18. Accessed 2024 at https://pubmed.ncbi.nlm.nih.gov/19322116/
Solano ME, Arck PC. Steroids, Pregnancy and Fetal Development. Front Immunol. 2020;10:3017. Published 2020 Jan 22. Accessed 2024 at https://pmc.ncbi.nlm.nih.gov/articles/PMC6987319/
Stefaniak M, Dmoch-Gajzlerska E, Jankowska K, et al. Progesterone and Its Metabolites Play a Beneficial Role in Affect Regulation in the Female Brain. Pharmaceuticals. 2023; 16(4):520. Accessed 2024 at https://pubmed.ncbi.nlm.nih.gov/37111278/
Mills EG, Yang L, Nielsen MF, et al. The Relationship Between Bone and Reproductive Hormones Beyond Estrogens and Androgens [published correction appears in Endocr Rev. 2021 Nov 16;42(6):872. doi: 10.1210/endrev/bnab024]. Endocr Rev. 2021;42(6):691-719. Accessed 2024 at https://pubmed.ncbi.nlm.nih.gov/33901271/

Backed by Science: Anhydrous VersaBase® HRT

Tue, 12 Nov 2024 14:48:13 GMT

At PCCA Science, we continuously build and grow scientific support for compounding and the technologies our members use in their practices. We test our bases using various methods before, during and after the release of a new product. We regularly submit results of these studies for publication in peer-reviewed journals and make them available to our members, who in turn can share them with prescribers, physicians and patients.

In Vitro Evaluation of the Percutaneous Absorption of Progesterone in Anhydrous Permeation-Enhancing Base Using the Franz Skin Finite Dose Model and Mass Spectrometry

What does the study say?

This study, published in the Archives of Dermatological Research, compares how well progesterone penetrates the skin in two topical formulations: one using Anhydrous VersaBase HRT and the second using a non-ionic cream. Results of the study showed that Anhydrous VersaBase HRT had a 3.2-fold increase in skin penetration over the non-ionic cream base, indicating it may be a good base to use in topical progesterone formulations.

Figure 1: The Anhydrous VersaBase HRT formulation offered a 3.2-fold increase in optical density (p = 0.029) for progesterone penetrating layers of skin compared to the non-ionic cream formulation.

What do the results of the study mean to prescribers and physicians?

Progesterone in a topical preparation using Anhydrous VersaBase HRT shows exceptional delivery of the hormone through the skin compared to the standard non-ionic cream base. It also indicates that the stability and potency of progesterone in the Anhydrous VersaBase HRT formulation was consistent for more than 180 days. Consistent hormone delivery is commonly recognized as achieving optimal prescriptive therapeutic outcomes for patients.

What do the results mean to patients?

The 180 beyond-use date (BUD) means patients will make fewer trips to the pharmacy for refills. Consistent hormone delivery may potentially help patients achieve a better therapeutic outcome.

What does anhydrous mean and why is that important?

Literally, anhydrous indicates a substance that contains no water. For compounded preparations, it means the water activity (Aw) — or the amount of available water in a substance — is less than 0.6 (<0.6). This is important because compounded preparations with Aw <0.6 do not support the growth of bacteria, yeast or molds.

Get a summary of study methods, images, graphs and more here.

*USP 795 establishes BUD limits by type of preparation in the absence of a USP−NF Compounded Preparation Monograph or CNSP-specific stability information.

Progesterone: Size Matters

PCCA offers USP-grade Special Micronized Progesterone with an unparalleled particle size to promote better bioavailability:

100% <9 microns
99% <5 microns
90% <2 microns

Additional Benefits

Consistently sourced from FDA-registered and GMP-compliant facilities
Tested in PCCA formulations in a range of concentrations
Above and beyond USP standards

Mitochondrial Health: The Key to Longevity?

Wed, 25 Sep 2024 17:34:52 GMT

In the race to unlock the secrets of longevity, one of the most exciting areas of research is mitochondrial health. These tiny organelles, often referred to as the "powerhouses" of the cell, are responsible for producing the energy (ATP) that fuels every cell in the body. As we age, mitochondrial function tends to decline, leading to reduced energy, increased oxidative stress and accelerated aging. Maximizing mitochondrial health has emerged as a key strategy for extending both lifespan and health span — how long we live and how well we live.¹

The Latest Breakthroughs in Mitochondrial Health

Recent research has identified several pathways to optimize mitochondrial function. One major discovery involves the molecule nicotinamide adenine dinucleotide (NAD+), which plays a crucial role in mitochondrial energy production.² As we age, NAD+ levels decline, leading to less efficient energy production and greater cellular damage. Boosting NAD+ through precursors like nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) has shown promise in improving mitochondrial function and extending the lifespan of various organisms in laboratory studies.³ How this translates to human longevity — that is the question!

Another fascinating area is mitophagy, the process by which cells clear out damaged or dysfunctional mitochondria. With age, the body's ability to efficiently remove these damaged mitochondria diminishes, leading to cellular dysfunction. Promoting mitophagy through intermittent fasting or caloric restriction can help maintain a population of healthy mitochondria, thereby improving metabolic efficiency and reducing oxidative stress. Compounds such as creatine and urolithin A have been shown to stimulate mitophagy, offering potential therapeutic benefits for aging populations.^4,5

Maximizing Mitochondrial Health for Longevity

Dietary Interventions: Nutrients like coenzyme Q10, alpha-lipoic acid and omega-3 fatty acids (especially from fresh fish) directly support mitochondrial energy production.⁶
Exercise: Regular physical activity, particularly high-intensity interval training (HIIT), has been shown to enhance mitochondrial biogenesis. It is interesting how FEW individuals in their 40s and older do exercises that really elevate their heart rate.⁷
Cold Exposure: Cold thermogenesis, or exposing the body to cold temperatures (e.g., ice baths or cold showers), stimulates the production of mitochondria and enhances their efficiency, offering a novel way to boost energy and longevity.⁸
Sleep and Stress Reduction: Poor sleep and chronic stress are mitochondrial toxins. Prioritizing restorative sleep and managing stress through practices like mindfulness meditation or yoga can promote mitochondrial repair and rejuvenation.⁹

Maintaining optimal hormone levels as we age plays a crucial role in supporting mitochondrial health. Hormones like estrogen, testosterone and thyroid hormones are vital regulators of mitochondrial function, helping to enhance mitochondrial biogenesis (the creation of new mitochondria) and optimize energy production. Adequate levels of these hormones, monitored through optimal testing, also promote mitochondrial repair.¹⁰

By integrating these strategies on a regular basis, we can enhance mitochondrial function, slow down the aging process and increase both lifespan and health span for a brighter, more energized future.

References

López-Otín C, Blasco MA, Partridge L, et al. Hallmarks of aging: An expanding universe. Cell. 2023;186(2):243-278. Accessed September 2024
Zhao Y, Zhang J, Zheng Y, et al. NAD+ improves cognitive function and reduces neuroinflammation by ameliorating mitochondrial damage and decreasing ROS production in chronic cerebral hypoperfusion models through Sirt1/PGC-1α pathway. J Neuroinflammation. 2021;18(1):207. Published 2021 Sep 16. Accessed September 2024 at https://pubmed.ncbi.nlm.nih.gov/34530866/
Lapatto HAK, Kuusela M, Heikkinen A, et al. Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study. Sci Adv. 2023;9(2):eadd5163. Accessed September 2024 at https://pubmed.ncbi.nlm.nih.gov/35276888/
Marshall RP, Droste JN, Giessing J, Kreider RB. Role of Creatine Supplementation in Conditions Involving Mitochondrial Dysfunction: A Narrative Review. Nutrients. 2022;14(3):529. Published 2022 Jan 26. Accessed September 2026 at https://pubmed.ncbi.nlm.nih.gov/35276888/
Pagano G, Pallardó FV, Lyakhovich A, et al. Aging-Related Disorders and Mitochondrial Dysfunction: A Critical Review for Prospect Mitoprotective Strategies Based on Mitochondrial Nutrient Mixtures. Int J Mol Sci. 2020;21(19):7060. Published 2020 Sep 25. Accessed September 2024 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582285/
Pagano G, Pallardó FV, Lyakhovich A, et al. Aging-Related Disorders and Mitochondrial Dysfunction: A Critical Review for Prospect Mitoprotective Strategies Based on Mitochondrial Nutrient Mixtures. Int J Mol Sci. 2020;21(19):7060. Published 2020 Sep 25. Accessed September 2024 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582285/
San-Millán I. The Key Role of Mitochondrial Function in Health and Disease. Antioxidants. 2023; 12(4):782. Accessed September 2024 at https://www.mdpi.com/2076-3921/12/4/782
Chung N, Park J, Lim K. The effects of exercise and cold exposure on mitochondrial biogenesis in skeletal muscle and white adipose tissue. J Exerc Nutrition Biochem. 2017;21(2):39-47. Accessed September 2024 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5545200/
Zielinski MR, Systrom DM, Rose NR. Fatigue, Sleep, and Autoimmune and Related Disorders. Front Immuno. 2019;10. Accessed September 2024 at https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.01827/full
Klinge CM. Estrogenic control of mitochondrial function. Redox Biol. 2020;31:101435. Accessed September 2024 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212490/

Managing Menopausal Weight Gain: The role estrogen plays with GLP-1 agonists

Wed, 11 Sep 2024 13:27:35 GMT

by Katy Hecker, PharmD, PCCA Clinical Services

In a woman’s life, the absence of menstruation for 12 months marks the official beginning of menopause. Waning ovarian function coupled with declining circulating hormone levels spark natural menopause, but menopause may also occur as result of surgical procedures such as following a hysterectomy and/or oophorectomy. Commonly reported symptoms of menopause include hot flashes, night sweats, vaginal dryness, sleep disturbances, mood swings and weight gain,¹ with an estimated 70% of menopausal women experiencing weight gain.²

Menopause and Body Composition

Menopause triggers body composition changes such as increased abdominal adipose tissue and decreased lean muscle mass. This change in body composition intensifies the risk of diabetes, cardiovascular disease, dyslipidemia (abnormal levels of lipids in the blood) and metabolic dysfunction-associated steatotic (fatty) liver disease. Heart disease is the leading cause of death in women; therefore, it is critical to address menopausal weight gain and the cardiometabolic changes that occur. Hormone replacement therapy, lifestyle modification and in some instances medication therapy may be beneficial to help combat menopausal weight gain.^2,3

GLP-1 and Weight Loss

GLP-1 is a hormone naturally produced in the central nervous system, intestine and pancreas. It is released in response to the consumption of fats and carbohydrates.^2,4GLP-1 increases insulin secretion, decreases glucagon release, slows gastric emptying and reduces food intake. Research also suggests it may reduce food reward behavior. The appetite suppressing effect of GLP-1 is due to its action in the hypothalamus and brainstem. Interestingly, this is the same region of the brain responsible for the food intake reduction effects of estrogen. Glucagon-like peptide-1 (GLP-1) receptor agonist and dual agonist therapies are FDA-approved for the treatment of obesity, weight management, type 2 diabetes mellitus and cardiovascular mortality reduction.⁴

Semaglutide and Hormone Replacement Therapy

Combining hormone replacement therapy with semaglutide, a GLP-1 receptor agonist, may lead to better outcomes for total body weight loss and subsequent improvements in cardiometabolic health. A recent retrospective review compared weight loss response and cardiometabolic changes in post-menopausal women using semaglutide in combination with and without hormone therapy. At three, six, nine and 12 months following semaglutide initiation, women using hormone therapy experienced approximately 30% greater total body weight loss than the non-hormone therapy users. Both groups showed improvements in cardiometabolic health marked by lower fasting blood glucose, blood pressure, LDL, total cholesterol and triglycerides.²

Reward Eating, GLP-1 and Estrogen

Reward eating is comprised of two categories, “wanting” and “liking.”⁵ Liking is associated with the palatability of the food and wanting is food craving triggered by a cue or stimuli which then leads to motivation to obtain a specific type of food.⁴ Research suggests women may exert a greater response to a centrally administered long acting GLP-1 agonist on food reward due to the activation of central estrogen receptor alpha. This reduction was noted with the “wanting” subtype of reward eating in women greater so than men. A reduction in the “liking” subtype of reward eating was displayed in both men and women. Administration of an estrogen receptor antagonist was sufficient to blunt the effects of the central GLP-1 agonist on food reward behavior in both men and women. This evidence suggests the activation of central estrogen receptor alpha may be critical for central GLP-1 agonist’s effect on reward eating.^4,5

Compounded Medications

There are many treatment strategies that may help menopausal women with the natural challenges and health risks associated with this phase of life. Combining therapies has yielded compelling results, and compounded medications can be personalized to meet the needs of each patient, offering a unique solution for various medication related concerns. For example, SubMagnaTM SL HMW can be used to deliver semaglutide in a sublingual dosage form. This may improve adherence in patients who have trouble swallowing or who are fearful of needles.

Members with clinical services access may contact our Clinical Services Team for help with PCCA formulas and other compounding questions.

References

World Health Organization. Menopause [Internet]. Oct 2022. Accessed August 2024 at https://www.who.int/news-room/fact-sheets/detail/menopause
Hurtado MD, Tama E, Fansa S, et al. Weight loss response to semaglutide in postmenopausal women with and without hormone therapy use. Menopause. 2024;31(4):266-274. doi:10.1097/GME.0000000000002310
Centers for Disease Control. About Women and Heart Disease [Internet]. May 15, 2024. Accessed August 2024 at https://www.cdc.gov/heart-disease/about/women-and-heart-disease.html#:~:text=Heart%20disease%20is%20the%20leading,affect%20women%20at%20any%20age
Elsevier Clinical Pharmacology. Glucagon-like Peptide-1 (GLP-1) Receptor Agonists and Dual Agonists [Internet]. Apr 9, 2024. Accessed August 2024 at https://elsevier.health/en-US/preview/glucagon-like-peptide-1-glp-1-receptor-agonists
Richard JE, Anderberg RH, Lopez-Ferreras L, et al. Sex and estrogens alter the action of glucagon-like peptide-1 on reward. Biol Sex Differ. 2016;7:6. doi:10.1186/s13293-016-0059-9

Antiaging: Estrogen and a Woman’s Skin

Wed, 31 Jul 2024 16:09:00 GMT

Studies show how estrogen deficiency in women decreases skin firmness, impairs wound healing, increases the number and depth of wrinkles, and contributes to skin thinning and dryness.

by Chelsea Turner, PharmD Candidate, Clinical Services Intern, and Beau Harger, PharmD, PCCA Clinical Compounding Pharmacist/Training Instructor

Skin aging can simply be defined as changes to the skin that occur due to growing older.¹ Oftentimes, many think skin aging correlates with chronological age; however, skin aging actually correlates to the period of estrogen deficiency, especially in menopausal women.² Studies indicate both collagen atrophy and estrogen deficiency have implications on the skin’s elasticity and firmness, as well as wrinkles.³ Estrogen replacement therapy might be an answer for aging skin, as it can increase collagen content, dermal thickness and elasticity; stimulate connective-tissue turnover; and decrease the likelihood of dry skin.⁴

Estrogen’s Role

Estrogen has more than 400 functions in a woman’s body and manifestations of estrogen deficiency may appear in various ways. In menopausal and postmenopausal women, estrogen deficiency is evidenced by decreased skin firmness, impaired wound healing, increased number and depth of wrinkles, skin thinning and skin dryness.

An extremely important role of estrogen is its relationship with structural components — collagen and elastin fibers — that naturally occur in human skin.

The reduction of collagen is traditionally considered the principal factor in the progressive degeneration of skin elasticity; retaining estrogen levels, however, inhibits collagen degradation by helping to maintain collagen balance. Elastin fibers are another structurally important component of skin that help prevent accelerated degenerative changes in the dermis. Studies indicate topical estrogen increases the number and thickness of elastic fibers in the skin.

One of the most common complaints from older women regarding their skin is dryness. Healthy skin requires a substantial amount of water content, which is significantly impacted by a woman’s menstrual cycle and age. Clinical studies indicate topical estrogen therapy can lead to increased water capacity by increasing naturally occurring moisturizing factors such as hyaluronic acid.² The activity of sebaceous secretions is also very important, as their activity is regulated by levels of circulating hormones. Estrogen replacement alone has a sebum-suppressive effect, which can decrease the size and number of sebaceous glands; the addition of progesterone, however, results in increased skin surface lipids.⁵

Topical Estrogen Replacement

The number of estrogen receptors is much greater in facial skin than in breast or thigh skin.⁶ Topical estrogens, such as estriol, have improved both elasticity and firmness, as well as decreased wrinkle depth and pore size by 61–100 percent, when applied to the face and neck.⁷

Compounded preparations offer individualized treatment options for patients and can include a wide variety of active pharmaceutical ingredients. For example, a formula of a topical estrogen, such as estriol, could be prescribed by a practitioner and compounded with VersaBase Cream by a pharmacist to potentially prevent signs of aging in the skin and possibly minimize systemic effects. VersaBase Cream is a great option for application to the face and neck, as it stimulates the natural moisturizing barrier through its emulsion system, leaving a soft and silky feel. VersaBase Cream is noncomedogenic, hypoallergenic, nonirritating and odor-free.

PCCA members with clinical services access may contact our Clinical Services team for help with antiaging formulas and other compounding concerns.

References

Wong, Q. Y. A., & Chew, F. T. (2021). Defining skin aging and its risk factors: a systematic review and meta-analysis. Scientific reports, 11(1), 22075. Accessed July 2024 at https://pubmed.ncbi.nlm.nih.gov/34764376/
Brincat, M. P., Baron, Y. M., & Galea, R. (2005). Estrogens and the skin. Climacteric : the journal of the International Menopause Society, 8(2), 110–123. Accessed July 2024 at https://pubmed.ncbi.nlm.nih.gov/16096167/
Calleja-Agius, J., Muscat-Baron, Y., & Brincat, M. P. (2007). Skin ageing. Menopause international, 13(2), 60–64. Accessed July 2024 at https://pubmed.ncbi.nlm.nih.gov/17540135/
Calleja-Agius, J., & Brincat, M. P. (2009). Effects of hormone replacement therapy on connective tissue: why is this important?. Best practice & research. Clinical obstetrics & gynaecology, 23(1), 121–127. Accessed July 2024 at https://pubmed.ncbi.nlm.nih.gov/19095501/
Sator, P. G., Schmidt, J. B., Sator, M. O., Huber, J. C., & Hönigsmann, H. (2001). The influence of hormone replacement therapy on skin ageing: a pilot study. Maturitas, 39(1), 43–55. Accessed July 2024 at https://pubmed.ncbi.nlm.nih.gov/11451620/
Punnonen, R., Lövgren, T., & Kouvonen, I. (1980). Demonstration of estrogen receptors in the skin. Journal of endocrinological investigation, 3(3), 217–221. Accessed July 2024 at https://pubmed.ncbi.nlm.nih.gov/7430556/
Schmidt, J. B., Binder, M., Demschik, G., Bieglmayer, C., & Reiner, A. (1996). Treatment of skin aging with topical estrogens. International journal of dermatology, 35(9), 669–674. Int J Pharm Compd. 1998;2(4):270-274. Accessed July 2024 at https://pubmed.ncbi.nlm.nih.gov/8876303/

From Sunburns to Campfire Burns: Prevention and Treatment of Summer Burns

Wed, 03 Jul 2024 19:47:08 GMT

Summer is synonymous with outdoor adventures, from basking in the sun to gathering around a campfire. However, these enjoyable activities can sometimes lead to unfortunate situations like burns, ranging from a mild sunburn to a more severe campfire burn. Understanding how to prevent and treat these burns is crucial to ensure a safe and enjoyable summer.

Sunburn: Causes and Prevention

Sunburns occur due to overexposure to ultraviolet (UV) rays from the sun. Several medications can predispose people to an elevated risk of sunburn, including thiazide diuretics, sulfonamides, fluoroquinolones, nonsteroidal anti-inflammatory drugs (NSAIDs), retinoids, tetracycline antibiotics such as doxycycline, and St. John's wort. Severity of a sunburn can range from mild redness to painful blistering and peeling.

To prevent sunburns, it's essential to use a broad-spectrum sunscreen with an SPF of at least 30. Applying sunscreen generously and reapplying every two hours, as well as after swimming or sweating, is crucial. Also, sunscreens do expire, so make sure to check the product’s expiration date. Seeking shade during peak hours, typically between 10 a.m. and 4 p.m., can significantly reduce your risk of sunburn. Wearing protective clothing, such as long-sleeved shirts, wide-brimmed hats and sunglasses, adds an extra layer of defense against harmful UV rays. Clothing and apparel accessories with an SPF rating have become popular as another barrier of skin protection. It is also important to maintain adequate hydration by drinking plenty of water as well as an appropriate amount of electrolytes to help keep your skin resilient against sun damage.1

Treatment for Sunburns

If you do get sunburned, prompt and effective treatment is essential. Start by taking a cool bath or shower to soothe the skin while avoiding soap or shower gel cleansers. Cleaning the skin with soap after sun exposure can be drying as it removes the oils from your skin, so cleansers should be avoided for a few days. After cooling down the affected area, apply aloe vera or moisturizer to keep the skin hydrated. Silicon-based gels, like PracaSil®-Plus or silicon sheets, can be used to hydrate the skin and potentially reduce discomfort. Over-the-counter pain relievers such as ibuprofen can help reduce pain and inflammation. A formula of a topical NSAID such as ketoprofen could be prescribed by a practitioner and compounded with PracaSil-Plus by a pharmacist to possibly minimize systemic effects. Drinking extra water with adequate electrolytes is vital to help your body recover from the dehydration caused by sunburn. Finally, avoid further sun exposure until your skin has fully healed to prevent additional damage.1

Campfire Burns: Risks and Prevention

Campfires are a beloved summer tradition, but they pose significant burn risks. With the increase in popularity of fire pits, childhood burns have increased and are one of the leading causes of preventable injuries in children. To enjoy campfires safely, maintain a safe distance from the fire and keep children and pets away. Using a designated fire ring or pit helps contain the fire and prevent it from spreading. Never leave a campfire unattended and always ensure it's completely extinguished before leaving the site. Keeping a bucket of water or a hose nearby is a good precaution in case of emergencies. Wearing appropriate clothing, avoiding loose garments that can easily catch fire, also adds to your safety.2

Treatment for Campfire Burns

Campfire burns require immediate action and attention. Start by running cool (not cold) water over the burn for 10-20 minutes to reduce pain and swelling. Protect the area with a clean, nonstick bandage or cloth. Avoid applying ice directly to the burn as it can cause further damage. Silicon-based gels, such as PracaSil-Plus or sheets, are excellent for covering the burn, helping to keep the wound moist and potentially reducing the risk of scarring. Over-the-counter pain relievers can help manage discomfort. For severe burns or if the burn is larger than the palm of the victim's hand, immediately seek professional medical help.3

Other Types of Burns

Aside from sunburns and campfire burns, summer activities can expose you to other types of burns. Be cautious around grills, stoves and hot sand. Using protective gear and being mindful of where you step and what you touch can prevent accidental burns. Additionally, be aware of pool chemicals and cleaning agents that can cause chemical burns.3 Always follow safety instructions and wear appropriate protective gear when handling these substances.

Burns, whether from the sun or a campfire, can be painful and potentially dangerous. By taking preventive measures and knowing how to treat burns effectively, you can enjoy your summer activities safely. Remember, prevention is always better than treatment, so take steps to protect yourself and your loved ones from summer burns. Stay safe and enjoy the sunny days!

References

Guerra, K. C., & Crane, J. S. (2023). Sunburn. In StatPearls. StatPearls Publishing. Accessed June 2024 at https://pubmed.ncbi.nlm.nih.gov/30521258/
Flaherty, M. R., & Sheridan, R. (2019). Fire Pit-Related Burn Injuries in Children and Adolescents. Journal of burn care & research : official publication of the American Burn Association, 40(6), 943–946. Accessed June 2024 at https://pubmed.ncbi.nlm.nih.gov/31289816/
Żwierełło, W., Piorun, K., Skórka-Majewicz, M., Maruszewska, A., Antoniewski, J., & Gutowska, I. (2023). Burns: Classification, Pathophysiology, and Treatment: A Review. International journal of molecular sciences, 24(4), 3749. Accessed June 2024 at https://pubmed.ncbi.nlm.nih.gov/36835171/

Biohacking Explained

Thu, 27 Jun 2024 20:26:54 GMT

Many unknowingly practice it on a daily basis. Others recognize it as a global movement. So what exactly is biohacking. So what exactly is biohacking?

Broadly speaking, biohacking is any method employed by an individual to enhance their health, performance and longevity. It can range from small diet and lifestyle changes to wearable devices or self-experimentation.¹

Although the first known use of the term “biohacking” occurred in 1992,² its practice took hold in the mid-2000s after genetic analysis became widely available and wearable devices became common and affordable. Individuals now use the vast amounts of physiological data generated from these and other technologies to improve their physical and mental performance, monitor their health and increase their lifespan.³

Prominent biohackers believe individuals can change their external and internal environments, resulting in full control of their biologic destiny.⁴Some believe biohacking leads to greater efficiencies and faster development of innovative therapeutics.⁵

General Types of Biohacking

Given its broad definition, the types of biohacking are endless. General types, however, have been defined and accepted by the biohacking community.

Lifestyle biohacking focuses on making positive health and behavior choices to embrace and increase biologic performance and longevity. For example, changing diets, practicing meditation and increasing exercise are all examples of lifestyle biohacking.

Molecular biohacking is the use of natural and synthetic substances to enhance biological functions. Substances include vitamins, minerals or peptides. Nootropics, also called smart drugs, are used to boost brain performance. Familiar over-the-counter nootropics include caffeine, L-theanine (an amino acid found in black and green teas), omega-3 fatty acids and ginkgo biloba.⁶

Technology-based biohacking includes wearable devices. Advanced devices — hyperbaric chambers or electromagnetic stimulators — are used for faster physiological changes or healing.³

Common Biohacking Practices and Real-World Applications

Dietary biohacking involves consumption of dietary supplements such as vitamins, minerals, prebiotics and probiotics to improve metabolism, boost energy production, improve physical performance, prevent chronic disease and increase lifespan. It can also include a specific type of diet — a ketogenic diet or intermittent fasting — for energy production and metabolism. Understanding nutrigenomics, or the relationship between a human genome, nutrition and health, is important. Some people also employ cellular metabolism monitoring devices such as glucose monitors or ketone breath analyzers.

Energy biohacking relates to sleep support and stress reduction. Light therapy is used to regulate the circadian rhythm, sleep tracking devices are used to monitor daily sleep patterns and meditation apps are used for sleep support and stress relief. Other techniques include consumption of vitamin B12 and magnesium supplements and wearing blue light protection glasses.

Physical health biohacking is popular among athletes to improve performance or expedite recovery from injuries. Common methods include cold therapy, heat therapy, whole body vibration therapy, pulsed electromagnetic field therapy, red light therapy for healing and consumption of supplements, electrolytes and energy drinks.

Age biohacking focuses on cellular senescence, or damaged cells. The goal is to improve longevity by inhibiting the production or reversing the process of cellular senescence and promoting cellular regeneration. Methods include red light therapy, stem cell therapy, cryotherapy, non-ablative laser therapy and consumption of antiaging and mitochondrial support supplements.

Brain biohacking combines exercise with nootropics to enhance cognitive efficiency. Other techniques include brainwave entrainment, transcranial magnetic stimulation therapy, neurofeedback therapy, brainwork and meditation.³

Learn more about how Dave Asprey, “The Father of Biohacking,” hacked his own health to transform his physicality, increase his IQ and reduce the total age of his biochemistry at ThinkNext International Seminar 2024.

References

Schroeder, K. (2022). Biohackers and DIY Gene Therapy. Front Line Genomics. Accessed June 2024 at https://frontlinegenomics.com/biohackers-and-diy-gene-therapy/
Merriam-Webster. (n.d.) Biohacking. In Merriam-Webster.com dictionary. Accessed June 2024 at https://www.merriam-webster.com/dictionary/biohacking#h1
Dutta, S.S. (n.d.) The Truth About Biohacking. News Medical Life Sciences. Accessed June 2024 at https://www.news-medical.net/health/The-Truth-About-Biohacking.aspx
Neumann, K.D. (2024) Biohacking: What Is It And How Does It Work? Forbes Health. Accessed June 2024 at https://www.forbes.com/health/wellness/biohacking/
Rasmussen, L. M., Guerrini, C. J., Kuiken, T., et al. (2020). Realizing Present and Future Promise of DIY Biology and Medicine through a Trust Architecture. The Hastings Center report, 50(6), 10–14. Accessed June 2024 at https://doi.org/10.1002/hast.1194
Berry, J. (2019) What are nootropics (smart drugs)? Medical News Today. Accessed June 2024 at https://www.medicalnewstoday.com/articles/326379

Potential Options for Migraine Patients

Wed, 12 Jun 2024 14:54:28 GMT

June is National Migraine and Headache Awareness Month and we want you to be well equipped to care for your migraine and headache patients.

by Catherine Henderson, PharmD, PCCA Clinical Compounding Pharmacist

Migraines affect roughly 14-15% of people globally each year and is just one of more than 200 headache disorders.¹ If you’ve ever been a migraine patient or treated a migraine patient, you know how challenging it can be to find the right treatment for acute migraines and the best prophylaxis for chronic migraines.

Acute Migraines

The current standard of care for acute migraine involves use of NSAIDs, ergotamine derivatives, triptans, gepants and ditans. Combination therapy with antiemetics and/or caffeine is also a mainstay of treatment.² With the loss of isometheptene from the market, many compounders have been searching for a replacement. Since there are so few options for treating migraines, losing an agent that is effective for some patients leaves a gap that can be difficult to fill.

In the PCCA Clinical Services department, we have recently helped many members find an alternative option for patients who were previously using isometheptene. The way that isometheptene is thought to work is by constricting the cranial arteries. Caffeine is another cranial vasoconstrictor, often used in migraine headache formulations.³For patients who were previously experiencing relief with isometheptene, caffeine would be a reasonable inclusion in their formula.

One of my favorite formulas to recommend for acute migraine is piroxicam 40 mg/ondansetron 2 mg/caffeine troches. The combination of ingredients treats pain and nausea associated with migraine headaches and may provide faster relief due to the route of administration. As an anhydrous formula, both compounders and patients can benefit from the potential of longer beyond-use dates (BUDs).*

Another unique compounding option for acute migraine is intranasal lidocaine, which has been shown to decrease pain intensity and the need for rescue medications. It has been used in varying concentrations of 4-10% in each nostril. The benefit of this formula is that it provides a non-oral, non-injectable route of administration that can be useful in patients experiencing significant nausea. Combining lidocaine with ketorolac in a nasal spray is another option that has been studied and found to have even greater pain relief than lidocaine alone.⁴ Before choosing this combination, it is important to remember that the use of ketorolac is limited to five days, regardless of route of administration. Evaluating the number of headache days per month that a patient has can help determine if this is an appropriate treatment.⁵

Migraine Prophylaxis

While the goals of therapy for acute migraine are to relieve symptoms as quickly as possible — with as few side effects as possible — we also need to avoid medication overuse headaches (a headache that results from the frequent use of acute medicines or painkillers).⁶ In any migraine patient, prevention is an important piece of the puzzle. Current migraine prophylaxis medications include beta-blockers (propranolol), anticonvulsants (valproate, topiramate), antidepressants (amitriptyline) and calcitonin gene-related peptide receptors (CGRPs) (erenumab).⁷ These prophylactic medications have varying success rates, with the new class of CGRPs having the greatest efficacy.⁸ Unfortunately, all of these medications come with the risk of adverse events and some come with a significant financial burden.

Alpha-lipoic acid and riboflavin are two agents that have been shown to help with migraine prophylaxis. A study found that a dose of riboflavin 400 mg/day for three months reduced headache days, as well as the duration, frequency and pain score of migraine attacks.⁹ Another study found similar results with alpha-lipoic acid 300 mg twice daily for 12 weeks.¹⁰ Alpha-lipoic acid has also been studied as a preventative agent in adolescents.¹¹A benefit of these two agents is that they are generally well-tolerated and may be less expensive than other options. These agents can be used alone or as an adjunct to other prophylactic measures.

Treatment Success

In helping your patients navigate migraine treatment and prophylactic options, there are some key strategies and counseling points to consider. Many patients expect full resolution of their migraine symptoms and frequency and may give up on a treatment option too soon if those expectations aren’t managed. Most prophylactic measures must be taken daily for at least two months before a determination can be made about the success of the treatment. Encourage patients to keep a headache diary to collect data about their headache days, severity and other details related to their migraines.⁶

As pharmacists, we are also uniquely placed to screen for potential medication overuse. Medication overuse headaches are typically seen in patients with 15 or more headache days per month. Most migraine prophylactics won’t be effective in these patients until they go through a detox period from acute migraine treatments.¹²The most effective detox programs for medication overuse headaches include complete withdrawal from acute treatments and initiation of preventative medications.^13,14

You have the opportunity to make a significant impact on the lives of your patients who suffer with debilitating headache disorders. This article covered just a few of the creative ways that compounding pharmacists are contributing to solutions for migraines.

PCCA members with clinical services access may contact our Clinical Services team for help when compounding for patients with migraines and other compounding concerns.

*USP 795 establishes BUD limits by type of preparation in the absence of a USP−NF Compounded Preparation Monograph or CNSP-specific stability information.

References

Steiner, T. J., & Stovner, L. J. (2023). Global epidemiology of migraine and its implications for public health and health policy. Nature reviews. Neurology, 19(2), 109–117. Accessed May 2024 at https://doi.org/10.1038/s41582-022-00763-1
Ailani, J., Burch, R. C., & Robbins, M. S. (2021). The American Headache Society Consensus Statement: Update on integrating new migraine treatments into clinical practice. Headache: The Journal of Head and Face Pain, 61(7), 1021–1039. Accessed May 2024 https://doi.org/10.1111/head.14153
Drugs.com (Last updated June 2023). Isometheptene, Caffeine, and Acetaminophen Tablets. Accessed May 2024 at https://www.drugs.com/pro/isometheptene-caffeine-and-acetaminophen-tablets.html
Chi, P. W., Hsieh, K. Y., Chen, K. Y., et al. (2019). Intranasal lidocaine for acute migraine: A meta-analysis of randomized controlled trials. PloS one, 14(10), e0224285. Accessed May 2024 at https://doi.org/10.1371/journal.pone.0224285
Pfaffenrath, V., Fenzl, E., Bregman, D., et al. (2012). Intranasal ketorolac tromethamine (SPRIX®) containing 6% of lidocaine (ROX-828) for acute treatment of migraine: Safety and efficacy data from a phase II clinical trial. Cephalalgia, 32(10), 766–777. Accessed May 2024 at https://doi.org/10.1177/0333102412451359
The Migraine Trust. (2021). Medication overuse headache. Accessed May 2024 at https://migrainetrust.org/understand-migraine/types-of-migraine/medication-overuse-headache/
Kumar, A., & Kadian, R. (2020). Migraine Prophylaxis. PubMed; StatPearls Publishing. Accessed May 2024 at https://www.ncbi.nlm.nih.gov/books/NBK507873/
Lampl, C., MaassenVanDenBrink, A., Deligianni, C.I. et al. The comparative effectiveness of migraine preventive drugs: a systematic review and network meta-analysis. J Headache Pain 24, 56 (2023). Accessed May 2024 at https://doi.org/10.1186/s10194-023-01594-1
Chen, Y.-S., Lee, H.-F., Tsai, C.-H., et al. (2021). Effect of Vitamin B2 supplementation on migraine prophylaxis: a systematic review and meta-analysis. Nutritional Neuroscience, 1–12. Accessed May 2024 at https://doi.org/10.1080/1028415X.2021.1904542
Kelishadi, M.R., Naeini, A.A., Khorvash, F. et al. The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines. Sci Rep 12, 271 (2022). Accessed May 2024 at https://doi.org/10.1038/s41598-021-04397-z
Puliappadamb, H. M., Satpathy, A. K., Mishra, et al. (2023). Evaluation of Safety and Efficacy of Add-on Alpha-Lipoic Acid on Migraine Prophylaxis in an Adolescent Population: A Randomized Controlled Trial. Journal of clinical pharmacology, 63(12), 1398–1407. Accessed May 2024 at https://doi.org/10.1002/jcph.2331
D'Amico, D., & Tepper, S. J. (2008). Prophylaxis of migraine: general principles and patient acceptance. Neuropsychiatric disease and treatment, 4(6), 1155–1167. Accessed May 2024 at https://doi.org/10.2147/ndt.s3497
Carlsen, L. N., Munksgaard, S. B., Jensen, R. H. et al. (2018). Complete detoxification is the most effective treatment of medication-overuse headache: A randomized controlled open-label trial. Cephalalgia : an international journal of headache, 38(2), 225–236. Accessed May 2024 at https://doi.org/10.1177/0333102417737779
Nielsen, M., Carlsen, L. N., Munksgaard, S. B., et al. (2019). Complete withdrawal is the most effective approach to reduce disability in patients with medication-overuse headache: A randomized controlled open-label trial. Cephalalgia, 39(7), 863–872. Accessed May 2024 at https://doi.org/10.1177/0333102419828994

The Vaginal Microbiome, Menopause & HRT

Thu, 09 May 2024 03:38:07 GMT

Menopause causes more than hot flashes, mood swing and changes in libido; it also impacts diseases caused by shifting changes in the vaginal microbiome. Bridget Briggs, MD, sheds light on the vaginal microbiome, its influences on a woman’s health throughout various life stages, as well as how HRT helps mediate changes — and associated diseases — in the vaginal microbiome during menopause.

by Dr. Bridget Briggs, PCCA HRT Symposium Keynote Speaker

The vaginal microbiome (VM) is a complex ecological system that includes commensal, symbiotic and pathogenic organisms that inhabit the vaginal surfaces and its cavity. These organisms include bacteria, viruses and fungi.

The composition of organisms within the VM changes throughout the various stages of a woman’s life:

Childhood: Corynebacterium spp., Escherichia coli (E. coli), and Mycoplasma spp. form the vaginal microbiome.
Puberty: At puberty, the vaginal microbial niche shifts toward other predominant colonies, including Lactobacillus spp., Atopobium and Streptococcus spp.
Reproductive Ages: During reproductive age, the vaginal microbiome houses a range of bacterial communities, including lactobacilli (L. crispatus, L. gasseri, L. jensenii and L. iners) along with anaerobic bacteria.
Menopause: Further changes in the composition of the VM include Gardnerella vaginalis, Ureaplasma urealyticum, Candida albicans and Prevotella spp., with a progressive decrease in species of lactobacillus.

VM and Lactobacillus

The composition of the vaginal microbiome can vary widely between individuals. It influences a woman’s reproductive health, immune responses and overall wellbeing. Imbalance in the microbiome is linked to bacterial vaginosis (BV), thrush (a common yeast infection), urinary tract infections (UTIs) and influences fertility.

Lactobacillus species dominate in a healthy vagina and are associated with cervicovaginal health. Disruption of the microbial status quo — notably during menopause — is associated with disease. Hormone replacement therapy (HRT), however, has shown to improve the vaginal microbiome:

Vaginal estradiol (E2) tablets resulted in substantial changes in the VM and metabolome with a lowering in pH, particularly in women with high-diversity bacterial communities at baseline.
Low pH moisturizer or placebo did not significantly impact the vaginal microbiota or metabolome despite lowering the vaginal pH.
Estradiol use may offer additional genitourinary health benefits to postmenopausal women.
A small randomized clinical trial of a vaginal probiotic in postmenopausal women found short-term decreases in proinflammatory gene pathways with increased vaginal lactobacilli.
A 2020 study conducted on 228 premenopausal women suggested that daily administration of a vaginal dose of Lactobacillus crispatus, after treatment with vaginal metronidazole, can reduce recurrence of bacterial vaginosis after 12 weeks.¹

Menopause, VM and Urinary Health

Decrease in lactobacillus results in an elevated vaginal pH and higher microbial diversity. Decreased levels may also cause vaginal epithelium atrophy (thinning of the vaginal epithelium), dyspareunia (painful intercourse), dysuria (pain when urinating) and other genitourinary symptoms of menopause (GSM), due in part from the changes in the local microenvironment.

GSM affects approximately 50% of postmenopausal women. A 2013 cross-sectional study (n = 87) showed that women with signs of mild or moderate vulvovaginal atrophy (VVA) had greater odds of having highly diverse microbiota depleted of lactobacilli than microbiota dominated by L. crispatus when compared to women with no VVA.
Use of HRT in menopause indicates the reversion of lactic acid bacteria (LAB) microbial diversity to premenopausal levels; use of HRT has also shown not to increase the prevalence of bacterial vaginosis in postmenopausal women.
Postmenopausal women have been found to display significantly lower levels of free glycogen than premenopausal women.²

Benefits of Estriol

A study on the effect of ultra-low dose estriol vaginal tablets (0.03 mg) and Lactobacillus acidophilus compared to placebo was investigated in 87 postmenopausal women. The instillation of lactobacilli and ultra-low dose estriol was found to significantly improve the vulvovaginal symptoms in these women.

A second study was conducted on 60 postmenopausal women, who were randomly assigned to receive oral isoflavone alone, isoflavone plus probiotic or hormonal replacement therapy (1 mg estradiol and 0.5 mg norethisterone acetate). After 16 weeks, the hormonal therapy group showed an increased number of lactobacilli in the vagina, similar to that seen in premenopausal state, and a decrease in vaginal pH. Conversely, no change in pH value was found in the isoflavone group and isoflavone plus probiotic group.¹

Impact of Progesterone on the VM

DMPA injection reduced total bacterial load and abundance of Gardnerella vaginalis.
Localized progesterone contraceptive also reduced lactobacillus abundance.
Progesterone inhibits vaginal epithelium proliferation. Lack of epithelial-derived glycogen in a progesterone-enriched environment may reduce lactobacillus and other bacterial abundance.
Due to increased levels of endogenous estrogen and progesterone during pregnancy, the contributions of exogenous progesterone may be obscured in pregnant women.¹

Additional Influences

The intestinal microbiota have a role in shaping the vaginal microbiota. Both are formed throughout the stages of development and are influenced by lifestyle, use of antibiotics and hormones; both produce metabolites that help guide the immune system to be tolerogenic (producing immunological tolerance) or pro-inflammatory. The use of antibiotics can have long lasting negative impacts on a person’s microbiome and promote chronic disease development. Various forms of oral, vaginal or fecal transplanted probiotics can help to influence disease states.

Interested in learning more?

Attend the July 18-19 HRT Virtual Conference, Winning with Weight Loss, Detox and the Microbiome. This highly engaging symposium features a lineup of experts shaping the field of HRT — including: Dr. Briggs; Carrie Jones, ND; Pamela Smith, MD, MPH, MS; Daniel Banov, RPh, MS; Sara Hover, RPh, FAARM; and Ranel Larson, PharmD.

References

Auriemma, R.S., Scairati, R., del Vecchio, G., et al. (2021). The Vaginal Microbiome: A Long Urogenital Colonization Throughout Woman Life. Front. Cell. Infect. Microbiol. 11. Sec. Microbiome in Health and Disease. Accessed July 2021 at https://www.frontiersin.org/articles/10.3389/fcimb.2021.686167/full
Meštrović, T., Matijašić, M., Perić, M., et al. (2020). The Role of Gut, Vaginal, and Urinary Microbiome in Urinary Tract Infections: From Bench to Bedside. Diagnostics (Basel, Switzerland), 11(1), 7. Accessed December 2020 at https://pubmed.ncbi.nlm.nih.gov/33375202/

Essential Supplements for Adults

Wed, 01 May 2024 19:37:37 GMT

In today's fast-paced world, maintaining optimal health can be a challenge. Despite the best intentions, many adults struggle to meet their nutritional needs through diet alone — that's where supplements can play a crucial role.

by Stephanie Allen, ASIN, DCN, DSS, CPES, Wellness Works Manager

Here are five supplements that adults should consider incorporating into their daily routine:

Multivitamin: According to the CDC, most Americans fall short of meeting their nutrient needs through diet alone. A high-quality multivitamin can help fill in the gaps, providing essential vitamins and minerals necessary for overall health and well-being.^1,2
Probiotic: A balanced microbiome in the gut is essential for digestive health, a robust immune system and even mood regulation. Probiotic supplements can help support the diversity of beneficial bacteria in the gut, promoting optimal gut function and overall wellness.^3-5
Fish Oil: Rich in omega-3 fatty acids EPA and DHA, fish oil supplements have been associated with numerous health benefits. The American Heart Association recommends a daily intake of at least 250 to 500 milligrams of EPA+DHA to support heart health and overall well-being.⁶
Vitamin D: Often referred to as the “sunshine vitamin,” vitamin D plays a crucial role in bone health, immune function and mood regulation. However, an estimated 88% of the population doesn't receive enough vitamin D from sunlight alone. Supplementation can help ensure adequate levels, especially for those who spend limited time outdoors or live in regions with limited sunlight.⁷
Magnesium: This essential mineral is involved in over 300 biochemical reactions in the body, including muscle function, nerve function and energy production. Despite its importance, studies suggest that approximately 75% of American adults don't meet the recommended daily intake of magnesium. Supplementation can help bridge this gap and support overall health and vitality.^8,9

While these supplements can be beneficial for many individuals, it's essential to remember that they are not a substitute for a balanced diet and healthy lifestyle. Additionally, it's always advisable to consult a healthcare professional before starting any new supplement regimen.

References

CDC. (Updated 2021). Only 1 in 10 Adults Get Enough Fruits or Vegetables. Accessed April 2024 at https://www.cdc.gov/nccdphp/dnpao/division-information/media-tools/adults-fruits-vegetables.html
U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans, 2020 - 2025. Accessed April 2024 at https://www.dietaryguidelines.gov/sites/default/files/2020-12/Dietary_Guidelines_for_Americans_2020-2025.pdf
Olvera-Rosales, L. B., Cruz-Guerrero, A. E., Ramírez-Moreno, E., et al. (2021). Impact of the Gut Microbiota Balance on the Health-Disease Relationship: The Importance of Consuming Probiotics and Prebiotics. Foods (Basel, Switzerland), 10(6), 1261. Accessed April 2024 at https://doi.org/10.3390/foods10061261
Appleton J. (2018). The Gut-Brain Axis: Influence of Microbiota on Mood and Mental Health. Integrative Medicine (Encinitas, Calif.), 17(4), 28–32. Accessed April 2024 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469458/
Hemarajata, P., & Versalovic, J. (2013). Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation. Therapeutic Advances in Gastroenterology, 6(1), 39–51. Accessed April 2024 at https://doi.org/10.1177/1756283X12459294
Williamson, L. (2023). Are you getting enough omega-3 fatty acids? American Heart Association News Stories. Accessed April 2024 at https://www.heart.org/en/news/2023/07/05/are-you-getting-enough-omega-3-fatty-acids
NIH Office of Dietary Supplements. (Updated 2023). Vitamin D Fact Sheet for Health Professionals. Accessed April 2024 at https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/
Schwalfenberg, G. K., & Genuis, S. J. (2017). The Importance of Magnesium in Clinical Healthcare. Scientifica, 2017, 4179326. Accessed April 2024 at https://doi.org/10.1155/2017/4179326
DiNicolantonio, J. J., O'Keefe, J. H., & Wilson, W. (2018). Subclinical magnesium deficiency: a principal driver of cardiovascular disease and a public health crisis. Open Heart, 5(1), e000668. Accessed April 2024 at https://doi.org/10.1136/openhrt-2017-000668

These statements have not been evaluated by the Food and Drug Administration. Products referenced in this article are not intended to diagnose, treat, cure or prevent any disease.

Decoding the Intricacies of Infertility

Wed, 24 Apr 2024 15:48:11 GMT

In recognition of National Infertility Awareness Week, April 21-27, PCCA Director of Clinical Services Sara Hover, RPh, FAARM, discusses how fertility is increasingly viewed as an indicator of overall health; how the intertwine of metabolic balance, hormone production and mitochondria impact fertility; as well as a way compounders can help those whose individual needs exceed commercially available medicines.

by Sara Hover, RPh, FAARM, PCCA Director of Clinical Services

In the complicated web of human biology, fertility stands as a vital sign, signaling the well-being of our reproductive health, as well as our overall health. Yet, behind the veil of conception lies a labyrinth of factors — from genetics to lifestyle — and even the most minute cellular processes. Infertility, a silent struggle for many, sheds light on the multifaceted nature of reproduction, intertwining with metabolic health, regulation of hormones — including estrogen and progesterone — mitochondrial function, as well as the important role that melatonin plays.

Fertility as a Vital Sign

Traditionally, vital signs such as heart rate, blood pressure and body temperature have served as indicators of overall health. However, fertility, often overlooked in routine medical assessments, is increasingly recognized as another crucial marker of well-being.¹ Heavy cramping is a red flag that there is a problem with nutrients, like magnesium, as well as a problem with the gut or hormonal imbalance.² While the ability to conceive may seem solely reproductive, it reflects broader physiological harmony within the body.

Reproduction and Metabolic Health

The interplay between reproductive health and metabolic well-being is profound. Research suggests that conditions such as obesity, insulin resistance and diabetes can significantly impact fertility. Metabolic imbalances disrupt hormonal equilibrium, impairing ovulation in women and sperm production in men.³Furthermore, excess adipose tissue can lead to the overproduction of estrogen, disrupting the delicate hormonal dance essential for conception.

Hormonal Balance

Estrogen and progesterone prepare the uterus for implantation. The changes that occur in the uterus have been termed endometrial receptivity. The window that is optimal for implantation of a fertilized egg is very narrow and for those patients with luteal phase defect — when the body prepares the uterus for pregnancy — the chances of being successful are greatly diminished.⁴Many women rely on progesterone to supplement the luteal phase of their cycle. Although there are many commercial product options, some may require a compounded prescription to meet their individual needs.

Adhering to the Vaginal Mucosa

Getting the hormone to adhere to the mucosal tissue is important, especially with progesterone and its need to maintain contact with the endometrium. One of our bases, MucoLox™ (PCCA #30-4782), is the perfect delivery vehicle because it adheres to the vaginal mucosal tissue, thereby increasing contact time with the mucosal surfaces. This makes it an ideal choice for use in vaginal compounded preparations.⁵

The Role of Mitochondria

Within the intricate machinery of cellular function, mitochondria emerge as powerhouse organelles crucial for energy production. Surprisingly, these tiny structures play a pivotal role in fertility. Mitochondria provide the energy needed for sperm motility, egg maturation and embryo development. Any compromise in mitochondrial function can undermine reproductive success, highlighting the intricate link between cellular health and fertility.^6,7

Mitochondria and Melatonin

Melatonin, often associated with sleep regulation, exerts profound effects on reproductive function. Emerging research suggests that melatonin receptors are present in the ovaries, testes and placenta, indicating involvement in reproductive processes. Moreover, melatonin's antioxidant properties safeguard reproductive cells from oxidative stress, essential for maintaining integrity and viability. Disruptions in melatonin signaling, whether due to sleep disturbances or environmental factors, can adversely affect fertility.^8-10

Putting It All Together

Infertility transcends mere reproductive challenges; it illuminates the intricate interplay between our bodies' myriad of systems. Understanding fertility as a vital sign underscores its significance in gauging overall health. From metabolic balance to mitochondrial function and the regulation of hormones like estradiol, progesterone and melatonin, every aspect of our physiology contributes to the delicate dance of conception. By unraveling the complexities of infertility, we pave the way for more holistic approaches to reproductive health, ensuring that every individual has the opportunity to embark on the journey of parenthood if desired.

References

Su, R.W., Fazleabas, A.T. (2015). Implantation and Establishment of Pregnancy in Human and Nonhuman Primates. Adv Anat Embryol Cell Biol.216:189-213. Accessed April 2024 at https://pubmed.ncbi.nlm.nih.gov/26450500/
Naraoka, Y., Hosokawa, M., Minato-Inokawa, S., et al. (2023). Severity of Menstrual Pain Is Associated with Nutritional Intake and Lifestyle Habits. Healthcare (Basel). 11(9):1289. Accessed April 2024 at https://pubmed.ncbi.nlm.nih.gov/37174831/
Marinelli, S., Napoletano, G., Straccamore, M., et al. (2022). Female obesity and infertility: outcomes and regulatory guidance. Acta Biomed. 93(4):e2022278. Accessed April 2024 at https://pubmed.ncbi.nlm.nih.gov/36043953/
Lessey, B.A., Young, S.L. (2019). What exactly is endometrial receptivity? Fertil Steril. 111(4):611-617. Accessed April 2024 at https://pubmed.ncbi.nlm.nih.gov/30929718/
PCCA Science. (2015). Evaluation of the Safety and Toxicological Profile of MucoLox: Human Oral Mucosa, Nasal Mucosa and Vaginal Mucosa (Part 3/3). PCCA Document #98929
Beikoghli, K.S., Kararigas G. (2022). Oestrogenic Regulation of Mitochondrial Dynamics. Int J Mol Sci. 23(3):1118. Accessed April 2024 at https://pubmed.ncbi.nlm.nih.gov/35163044/
May-Panloup, P., Chretien, M-F., Malthiery, Y., et al. (2007). Mitochondrial DNA in the Oocyte and the Developing Embryo. Curr Top Dev Biol. 77:51-83. Accessed April 2024 at https://www.sciencedirect.com/science/article/abs/pii/S007021530677003X?via%3Dihub
Reiter, R.J., Sharma, R., Romero, A,, et al. (2023). Aging-Related Ovarian Failure and Infertility: Melatonin to the Rescue. Antioxidants (Basel). 12(3):695. Accessed April 2024 at https://pubmed.ncbi.nlm.nih.gov/36978942/
Batıoğlu, A.S., Sahin, U., Gürlek, B., et al. (2012). The efficacy of melatonin administration on oocyte quality. Gynecol Endocrinol. 28(2):91-3. Accessed April 2024 at https://pubmed.ncbi.nlm.nih.gov/21770829/
Tamura ,H., Takasaki, A., Miwa, I., et al. (2008). Oxidative stress impairs oocyte quality and melatonin protects oocytes from free radical damage and improves fertilization rate. J Pineal Res. 44(3):280-7. Accessed April 2024 at https://pubmed.ncbi.nlm.nih.gov/18339123/

Unraveling the Enigma of Vulvodynia: Signs, Symptoms and Ways to Manage

Wed, 07 Feb 2024 20:46:57 GMT

by Sara Hover, RPh, FAARM, PCCA Director of Clinical Services

Signs and Symptoms of Vulvodynia

Persistent vulvar pain, burning sensations and discomfort define the landscape of vulvodynia, affecting everyday activities — including intimacy. Although many patients will report symptoms of recurring vaginitis, laboratory results prove negative. Often, these patients will experience pain triggered by undergarments or tight-fitting pants in contact with their vulva, or even when sitting for prolonged periods of time. It is essential to rule out other potential causes of vulvar pain before confirming vulvodynia, as it is a diagnosis of exclusion.¹

Pelvic Floor Dysfunction and Vulvodynia

The intricate interplay between vulvodynia and pelvic floor dysfunction underscores the complexity of this condition. Chronic tension or weakness in the pelvic floor muscles can exacerbate vulvar pain, creating a cycle of discomfort that necessitates comprehensive management.³

Pelvic Floor Physical Therapy

A cornerstone in vulvodynia management should include physical therapy protocols, such as vulvar desensitization, pelvic floor muscle stretching, myofascial release, conjunctive tissue manipulation and neuromuscular re-education. There are also similar techniques to help release the hip and abdominal muscles. This therapy has been found to alleviate pain and promote overall pelvic health. There are physical therapists that specialize in pelvic floor disorders.³

Topical Medications for Vulvodynia

Topical medications, including local anesthetics like lidocaine or compounded creams with medications such as amitriptyline, baclofen and gabapentin, play a crucial role in reducing vulvodynia symptoms. Amitriptyline is a tricyclic antidepressant which may relieve neuropathic pain by its unique ability to inhibit presynaptic reuptake of serotonin and noradrenaline.⁴ Baclofen is a gamma-aminobutyric acid type B (GABA-B) receptor agonist and may also produce anti-glutamate action, both of which inhibit nociceptive signaling in cutaneous nerve fibers. It is most appropriate for use in patients with concurrent pelvic hypertonia.⁵ Gabapentin works on the voltage‐dependent calcium ion channels, which results in reduced neuropathic pain. In a retrospective chart review, gabapentin cream was well tolerated and significantly reduced vulvar pain.⁶

Acupuncture: A Holistic Approach

Acupuncture, a traditional Chinese practice where needles are skillfully applied to specific acupoints to harmonize the body's energy flow, offers a holistic approach to vulvodynia management. Acupuncturists target specific acupoints on the abdomen — suprapubically —and the extremities, avoiding direct application to the vulva. The ancient art of acupuncture is believed to move blocked qi (energy), relax pelvic floor muscles, and reduce pain and heat in the vulvar region.¹ While more research is needed, the anecdotal evidence and some studies suggest that acupuncture may play a valuable role in alleviating vulvodynia symptoms.

Multidimensional Approach

Vulvodynia demands a multidimensional approach to treatment, encompassing an understanding of its signs and symptoms, acknowledging the connection with pelvic floor dysfunction and exploring diverse management options. From topical medications to pelvic floor physical therapy and the holistic embrace of acupuncture, women navigating the challenges of vulvodynia have an array of tools at their disposal. If you suspect a patient may have vulvodynia, discuss their management options and recommend that she seek guidance from a healthcare professional.

References

Schlaeger, J. M., Glayzer, J. E., Villegas-Downs, M., et al. (2023). Evaluation and Treatment of Vulvodynia: State of the Science. Journal of midwifery & women's health, 68(1), 9–34. https://doi.org/10.1111/jmwh.13456
Bornstein J., Goldstein A.T., Stockdale C.K., et al. 2015 ISSVD, ISSWSH and IPPS Consensus Terminology and Classification of Persistent Vulvar Pain and Vulvodynia. Obstet Gynecol. 2016;127(4):745‐751. https://doi.org/10.1097/AOG.0000000000001359
Morin, M., Dumoulin, C., Bergeron, S., et al. (2021). Multimodal physical therapy versus topical lidocaine for provoked vestibulodynia: a multicenter, randomized trial. American journal of obstetrics and gynecology, 224(2), 189.e1–189.e12. https://doi.org/10.1016/j.ajog.2020.08.038
Sindrup, S. H., Otto, M., Finnerup, N. B., et al. (2005). Antidepressants in the treatment of neuropathic pain. Basic & clinical pharmacology & toxicology, 96(6), 399–409. https://doi.org/10.1111/j.1742-7843.2005.pto_96696601.
Keppel Hesselink, J. M., Kopsky, D. J., & Sajben, N. L. (2014). Vulvodynia and proctodynia treated with topical baclofen 5 % and palmitoylethanolamide. Archives of gynecology and obstetrics, 290(2), 389–393. https://doi.org/10.1007/s00404-014-3218-4
Boardman, L. A., Cooper, A. S., Blais, L. R., et al. (2008). Topical gabapentin in the treatment of localized and generalized vulvodynia. Obstetrics and gynecology, 112(3), 579–585. https://doi.org/10.1097/AOG.0b013e3181827c77

Autoimmune Thyroid Diseases

Thu, 25 Jan 2024 15:03:30 GMT

Although January is National Thyroid Month, our Clinical Services team gets a lot of queries throughout the year on managing thyroid patients, including those with autoimmune conditions such as Graves’ disease (GD) and Hashimoto's thyroiditis (HT). While thyroid clinical management may seem complicated, understanding some basics of thyroid physiology and the pathophysiology of these autoimmune diseases may help make a difference in patients’ lives.

by Nat Jones, RPh, FAPC, PCCA Clinical Compounding Pharmacist

The thyroid gland produces hormones that serve as the master in energy production and affects almost everything we do. When dysfunctional thyroid performance occurs, the impact can be devastating. Many patients on thyroid replacement therapy (TRT) are still not happy with how they feel.

Thyroid Functions and Synthesis

The thyroid gland produces three main hormones: triiodothyronine (T3), thyroxine (T4) and calcitonin. Monitoring levels of T4 and T3 occur in the hypothalamus and pituitary gland. Thyrotropin-releasing hormone (TRH) produced by the hypothalamus stimulates the pituitary gland to secrete the thyroid-stimulating hormone (TSH), which stimulates both production and secretion of T4 and T3. T4 and T3 then travel in the blood to every cell in the body, including the hypothalamus and pituitary as feedback for production. A TSH test reflects the brain’s assessment of both T4 and T3 levels. A high TSH level usually indicates low levels of the hormones — or hypothyroidism — and a low TSH usually indicates high hormone levels — or hyperthyroidism.

Synthesis of thyroid hormones occurs in the thyroid gland from the substrate of the amino acid tyrosine and iodine. Thyroglobulin (TG) is a large glycoprotein used as the matrix for thyroid hormone synthesis. Ingested iodide is trapped in the thyroid, oxidized and bound to tyrosine to form iodothyronines in thyroglobulin; coupling of iodotyrosyl residues forms T4 and T3. The process requires the presence of iodide, a peroxidase (TPO), a supply of hydrogen peroxide (H2O2), and an iodine acceptor protein (Tg).¹

T4 is the major producer and considered a prohormone to T3, the most active form. T4 is converted via the 5’-deiodinase enzymes into T3 and is also converted via the 5-deiodinase into reverse T3 (rT3), an inactive competitor. The role of rT3 is to act as a metabolic governor to help slow energy production — stress increases rT3 production. T3 works at the inner membrane of the mitochondria to stimulate oxidative phosphorylation.

Inadequate T3 presence in the mitochondria results in hypothyroidism, where ATP production suffers and body temperature decreases. If a patient cannot convert T4 to T3 adequately, then supplementation should ideally include both hormones — not just T4. Low selenium can also decrease the conversion of T4 to T3 via the 5’-deiodinase enzyme. In addition, low ferritin (the intracellular storage form of iron) can decrease T4 to T3 conversion. Decades of menstruation and subsequent iron loss is likely one of the functional reasons why more females than males have low conversion.

The basic principle of the (unidirectional) reductive sequential monodeiodinations of iodothyronines. T4 secreted by the thyroid gland can be deiodinated at the 5’-position of its phenolic ring by DIO1 and DIO2 yielding the main thyromimetic hormone T3. Enzymatic removal of the iodine substituent in 5’-position of the tyrosyl-ring of T4 by either DIO3 or DIO1 produces reverse-T3 (rT3), which is devoid of thyromimetic activity but circulates in the blood.²

Hashimoto's Thyroiditis

In HT, antibodies produced against TPO (TPO Ab) attack normal thyroid tissue. Initially, there can be a hyperthyroid release of hormone from the gland; over time the production falls and usually becomes fixed hypothyroidism, requiring thyroid hormone supplementation. It is important to note that you cannot “top off the tank” with a portion of T4 and/or T3 needed — negative feedback will ultimately decrease production, so full supplementation should be the goal from the beginning of therapy. HT is 4.4 times more likely to occur in women than men and affects 1 to 2 percent of people in the United States.³

Graves’ Disease

GD, which represents 60-80% of all cases of hyperthyroidism, is caused by the production of immunoglobulin G (IgG) autoantibodies and thyroid-stimulating immunoglobulin (TSI) — also known as thyroid-stimulating antibody (TSAb).⁴These antibodies bind to and activate the receptor, causing the autonomous production of thyroid hormones — hyperthyroidism — as well as thyroid growth. Thyroid growth can cause a diffuse goiter, possibly exophthalmia and bone loss. The standard treatment for GD is antithyroid drugs such as methimazole or propylthiouracil. Many GD patients require surgery or radio ablation to remove the gland, after which thyroid replacement therapy (TRT) is needed. GD is more common in women than men, with onset occurring between ages 20 to 50 years.

Issues and Options

There is debate about replacing T4 alone or combinations of T4 and T3 in any ratio, and whether it is best to formulate T4 and T3 in a slow-release capsule using methocel E4M. The half-life of T4 is very long, about 7 days, so a slow-release formulation is not needed. Several T4 commercial options are currently available, and many pharmacists focus on compounding and titrating T3 to accompany commercial T4 products.

Food and beverage interfere with TRT absorption.⁵ Compounding a slow-release capsule size #1 or larger, which dissolves between 8 to 10 hours, presents multiple occasions for consumption of food and beverage that lead to erratic absorption. Many patients with inflamed GI tracts may have poor absorption of thyroid hormones, also favoring a prompt (immediate) release formulation for better clinical outcome.

Another compounding option is Thyroid USP from desiccated porcine thyroid gland, which contains both T4 and T3 along with calcitonin and iodine in trace amounts. This full complement of hormones is favored by some patients for symptomatic control. The ratio of T4 to T3 in porcine thyroid is roughly 4.2:1. Immediate-release capsule formulas are the most commonly compounded.

Address the Underlying Problem

An important note with either disease: when a patient’s thyroid levels and subsequent symptoms get to the point where TRT is needed, addressing the underlying autoimmune disease has probably not been done! Although the patient is getting thyroid hormones, the immune system has not been corrected. So how do we address this?

There is much evidence that gut dysbacteriosis, bacterial overgrowth and increased gut permeability favor the development of HT, and it has been suggested that the thyroid–gut axis may influence our overall metabolism.^6,7 In addition, the results of a recent meta-analysis investigating the effect of a gluten-free diet (GFD) seem to indicate a positive effect on thyroid function and its inflammation, particularly in patients with HT.⁷

As such, you may want to advise TRT patients to avoid proinflammatory foods such as gluten and implement gut restoration protocols — including probiotics — to reinoculate the intestines. Healing the lining with supplements such as L-glutamine could also have positive effects on clinical outcome. In addition, low-dose naltrexone (LDN) therapy is a good way to help correct GI inflammation and improve immune function.

Maintaining appropriate thyroid levels in TRT patients can be tricky, even overwhelming. Members with clinical services may contact our Clinical Services team for help with dosage recommendations, lab interpretations and other concerns.

References

Rousset, B., Dupuy, C., Miot, F., & Dumont, J. (2015). Chapter 2 Thyroid Hormone Synthesis And Secretion. In K. R. Feingold (Eds.) et. al., Endotext. MDText.com, Inc. Accessed 2024 at https://pubmed.ncbi.nlm.nih.gov/25905405/
KÖhrle, J., Frädrich, C. (2022) Deiodinasees control local cellular and systemic thyroid hormone availability. Free Radical Biology and Medicine, 193:1. Open access publication. Accessed 2024 at https://www.sciencedirect.com/science/article/pii/S0891584922006062#fig1
NIH National Library of Medicine, (updated 2020) Hashimoto’s Disease. Accessed 2024 at https://medlineplus.gov/genetics/condition/hashimotos-disease/#resources
Pokhrel, B., & Bhusal, K. (2023). Graves Disease. In StatPearls. StatPearls Publishing. Accessed 2024 at https://www.ncbi.nlm.nih.gov/books/NBK448195/
Liu, H., Lu, M., Hu, J., et al. (2023). Medications and Food Interfering with the Bioavailability of Levothyroxine: A Systematic Review. Thera Clin Risk Manag. 19, 503–523. Accessed 2024 at https://doi.org/10.2147/TCRM.S414460
Fröhlich, E., & Wahl, R. (2019). Microbiota and Thyroid Interaction in Health and Disease. Trends in endocrinology and metabolism: TEM, 30(8), 479–490. Accessed 2024 at https://doi.org/10.1016/j.tem.2019.05.008
Knezevic, J., Starchl, C., Tmava Berisha, A., et al. (2020). Thyroid-Gut-Axis: How Does the Microbiota Influence Thyroid Function?. Nutrients, 12(6), 1769. Accessed 2024 at https://doi.org/10.3390/nu12061769
Piticchio, T., Frasca, F., Malandrino, P., et al. (2023). Effect of gluten-free diet on autoimmune thyroiditis progression in patients with no symptoms or histology of celiac disease: a meta-analysis. Frontiers in endocrinology, 14, 1200372. Accessed 2024 at https://doi.org/10.3389/fendo.2023.1200372

Unraveling the Connection: VAT, Estradiol, Cognitive Health & Menopause

Wed, 17 Jan 2024 15:13:49 GMT

by Sara Hover, RPh, FAARM, PCCA Director of Clinical Services

In both men and women, the presence of VAT has been associated with an increased risk of compromised brain network structure and cognitive impairment. However, a fascinating discovery emerges when exploring the role of estradiol, a key female sex hormone, in mitigating the negative consequences of VAT, particularly in women during midlife.¹

Visceral Adipose Tissue and Cognitive Impairment

Visceral adipose tissue, the fat stored around internal organs, has long been implicated in various health conditions. Recent studies have uncovered its association with compromised brain network structure and cognitive decline. Both men and women with higher levels of VAT exhibit an increased risk of cognitive impairment, highlighting the importance of understanding the interplay between body composition and brain health.²

Women in Midlife: Accelerated Cognitive Aging and VAT

Notably, women during midlife face a unique set of challenges associated with changes in hormonal balance while transitioning into menopause. The presence of VAT during this phase has been linked to accelerated cognitive aging, possibly due to association with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. This suggests that the impact of VAT on cognitive function is particularly pronounced during the transition to menopause and the years that follow. Excess stress — and losing hormones is a stressor — can lead to metabolic changes resulting in weight gain. It has been noted that there is a significant relationship between the overactivity of the HPA axis and abdominal fat and/or metabolic syndrome. Chronic stress could lead to the development of obesity.³ VAT amplifies the negatives associated with age including cognitive health. It has been hypothesized that estradiol reduces the negative effects of VAT in women.

Estradiol's Protective Role Gets an A: Anti-Inflammatory, Anti-Apoptotic and Antioxidant

Amidst the concerning findings related to VAT and cognitive aging in women, the role of estradiol emerges as a potential protective factor. Estradiol, a form of estrogen, is known for its multifaceted functions in the female body. Research suggests that estradiol levels may play a crucial role in mitigating the negative consequences of VAT on brain structure and function.

First, it has been found that estradiol has anti-inflammatory properties. When women go through menopause, either naturally or surgically, many experience systemic inflammation. Neuroinflammation has negative effects on cognition.⁴ Estradiol is vasodilatory and thus promotes blood flow to the brain, therefore enhancing circulation. The delivery of oxygen and nutrients to the brain supports overall brain health. Another important function of estradiol is how it functions as an anti-apoptotic agent. Apoptosis, or programmed cell death, is a natural process in the body, but estradiol helps to prevent excessive cell death in the brain, preserving its integrity. Lastly, estradiol has antioxidant properties that help reduce oxidative damage to the brain. Oxidative stress is a common factor in age-related cognitive decline. Estradiol combats this to protect the brain.

Preserving Myelin Architecture: A Key Aspect of Cognitive Health

Myelin, the protective sheath around nerve fibers, is crucial for efficient neural communication. Research suggests that estradiol may play a vital role in preserving myelin architecture. This preservation is essential for maintaining the integrity of neural pathways and ensuring optimal cognitive function. Low-estrogen states, such as menopause, have long been recognized as a time where more women experience exacerbations of myelin-related diseases such as multiple sclerosis (MS).⁵ Therefore, estradiol’s role in protecting the myelin sheath has been the center of research in MS, but this research also has application for brain health and cognition.¹

Complex Interplay

The intersection of visceral adipose tissue, estradiol levels and cognitive health in women during midlife reveals a complex interplay with profound implications. VAT's association with compromised brain network structure and accelerated cognitive aging underscores the need for a holistic approach to health during this critical phase. The protective effects of estradiol, including vasodilation, anti-apoptosis and antioxidation, offer a ray of hope in understanding and potentially mitigating the cognitive consequences of VAT. As research continues to unfold, recognizing the importance of hormonal balance and lifestyle factors becomes paramount in promoting cognitive well-being, particularly for women navigating the intricate journey of midlife.

References

Zsido, R. G., Heinrich, M., Slavich, G. M., et al. (2019). Association of Estradiol and Visceral Fat With Structural Brain Networks and Memory Performance in Adults. JAMA network open, 2(6), e196126. Accessed January 2024 at https://doi.org/10.1001/jamanetworkopen.2019.6126
Anand S.S., Friedrich M.G., Lee D.S., et al. (2022) Evaluation of Adiposity and Cognitive Function in Adults. JAMA Netw Open. 5(2):e2146324. Accessed January 2024 at https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2788555
Vicennati, V., Pasqui, F., Cavazza, C., Pagotto, U., & Pasquali, R. (2009). Stress-related development of obesity and cortisol in women. Obesity (Silver Spring, Md.), 17(9), 1678–1683. Accessed January 2024 at https://doi.org/10.1038/oby.2009.76
Villa, A., Vegeto, E., Poletti, A., & Maggi, A. (2016). Estrogens, Neuroinflammation, and Neurodegeneration. Endocrine reviews, 37(4), 372–402. Accessed January 2024 at https://doi.org/10.1210/er.2016-1007
Christianson, M. S., Mensah, V. A., & Shen, W. (2015). Multiple sclerosis at menopause: Potential neuroprotective effects of estrogen. Maturitas, 80(2), 133–139. Accessed January 2024 https://doi.org/10.1016/j.maturitas.2014.11.013

THE PCCA BLOG

The FDA Removes the Black Box Warning on Estrogen: What Pharmacists Need to Know (2025 Update)

How We Got Here: The Women’s Health Initiative (WHI) and the “HRT Fear” Era

Key WHI findings (as widely interpreted at the time):

What Exactly Is the FDA Changing in 2025?

What This Means for Pharmacists: Counseling That’s Accurate, Individualized, and Confidence-Building

Bottom Line for Pharmacy Practice

References

Illuminating Stealth Syndromes

Summary of Syndromes

MCAS (Mast Cell Activation Syndrome)

POTS (Postural Orthostatic Tachycardia Syndrome)

EDS (Ehlers-Danlos Syndrome)

Compassion and Concern: The LDN Research Trust

Help Spread Awareness

Watch the compelling trailer for “Understanding Stealth Syndromes”. Click Here.

To purchase one or more licenses for the documentary, Click Here.

References

Bacterial Vaginosis: A Persistent Challenge

Common and Uncommon Pathogens

Diagnosis and Compounding Options

Ellage® Anhydrous Vaginal: The Base of Choice

References

Easing Drug & Disease Side Effects in Hospice Patients

ABH Gel: Common & Customized

Studied Results: PermE8® Anhydrous Gel

References

Balance Hormones and Grow Your Practice

Introducing PCCA Master Courses: HRT

Earn Your Certified Master Designation in HRT

References

Microdosing GLP-1 RAs: Fad or Forever?

Looking Back on GLP-1 RAs

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What Is Microdosing?

Endogenous GLP-1 vs. Exogenous GLP-1 RAs

Microdosing GLP-1 RAs

References

A Personalized Approach to HRT for Perimenopausal Women

Understanding Estrogen Levels in Perimenopause

The Role of Cortisol in Perimenopausal Health

Progesterone: The Balancing Hormone

Benefits of a Personalized HRT Approach

References

Backed by Science: Anhydrous VersaBase® HRT

In Vitro Evaluation of the Percutaneous Absorption of Progesterone in Anhydrous Permeation-Enhancing Base Using the Franz Skin Finite Dose Model and Mass Spectrometry

What does the study say?

What do the results of the study mean to prescribers and physicians?

What do the results mean to patients?

What does anhydrous mean and why is that important?

Progesterone: Size Matters

Mitochondrial Health: The Key to Longevity?

The Latest Breakthroughs in Mitochondrial Health

Maximizing Mitochondrial Health for Longevity

References

Managing Menopausal Weight Gain: The role estrogen plays with GLP-1 agonists

Menopause and Body Composition

GLP-1 and Weight Loss

Semaglutide and Hormone Replacement Therapy

Reward Eating, GLP-1 and Estrogen

Compounded Medications

References

Antiaging: Estrogen and a Woman’s Skin

Estrogen’s Role

Topical Estrogen Replacement

References

From Sunburns to Campfire Burns: Prevention and Treatment of Summer Burns

Sunburn: Causes and Prevention

Treatment for Sunburns

Campfire Burns: Risks and Prevention

Treatment for Campfire Burns

Other Types of Burns

References

Biohacking Explained

General Types of Biohacking

Common Biohacking Practices and Real-World Applications

References

Potential Options for Migraine Patients

Acute Migraines

Migraine Prophylaxis

Ellage^® Anhydrous Vaginal: The Base of Choice

Studied Results: PermE8^® Anhydrous Gel