Hormone Replacement Therapy: Justifications for Compounded Bioidentical Options

Prescribers and regulators may question the clinical need of compounded bioidentical hormone therapies (cBHT) and how they differ from FDA approved drug products. With changing times, offering compounded hormone replacement therapies has become more challenging, especially with the availability of FDA-approved bioidentical hormone replacement therapy options (e.g., estradiol creams and patches, progesterone capsules, etc.).

Compounding pharmacists still have an advantage in preparing patient-specific preparations and understanding hormone receptors, including the discovery of estrogen receptor beta, has shown to have significant clinical utility.

Compounded Hormone Replacement Therapy (HRT) Discussions and Critique

As the use of compounded hormone replacement therapy (HRT) has grown and become well-established, its value and efficacy have been a topic of discussion and critique in various medical forums. Some healthcare providers for instance may be educated by platforms that see little unique value in compounded HRT, while others depend greatly on personalized options for enhanced patient outcomes.

Compounding pharmacies commonly offer, for example, topical estrogen therapies to patients who need a preparation in a different strength, combination, or base than what is commercially available or to those that have a skin reaction to an estradiol patch.

Compounding pharmacists have seen a growth in their understanding of what hormones do and how they work, particularly in relation to hormone replacement therapy for the treatment of menopausal symptoms.

Although compounds are not FDA-approved, compounded HRT is a type of precision medicine formulated into a myriad of dosing, dosage forms, and ingredient options to fill a clinical need for certain patients.

Compounding originally revolved around using hormones identical to those produced in the human body, unlike synthetic hormones or those found in horses. The argument for compounding identical hormones is no longer as useful, given the number of estradiol (E2) products available in topical forms, but the differences between those and what compounders offer are still unique and significant.

Estrogen Receptor(s) and Discovery

In 1996, a research team in Sweden discovered estrogen receptor beta (ERβ), a finding that was initially overlooked but has since gained a reputation. Prior to the discovery, most research focused on estrogen receptor alpha (ERα) and its actions.

ERα and ERβ are structurally similar but differ slightly, affecting the binding affinities of various estrogens. Estradiol (E2), the primary estrogen in premenopausal women, binds to both receptors with approximately equal affinities, while estriol (E3) primarily binds to ERβ.

This distinction is significant, and current research is actively investigating the role of ERβ.

Although there is also useful information on estrone (E1), it is not commonly included in compounded formulas.

Estriol (E3) Is One of The Main Forms of Binding and Still Under Research

ERβ has been the focus of much research due to its different activity realm from ERα. Estradiol (E2) and estriol (E3), the two main forms of estrogen, bind differently to ERα and ERβ due to the slight differences in their structures. E3 binds almost exclusively to ERβ, which has led to its characterization as weaker than E2.

E3 has been found to have both agonistic and antagonistic actions, especially in relation to E2. When given alone, E3 has an estrogenic effect whose magnitude depends on the dosage, but when given with E2, it may exert antagonistic effects.

Unlike E2, E3 has not been found to increase breast density in studies. In rat studies, intermittent implantation of E3 subcutaneously has been shown to reduce the development of chemically-induced breast cancer by 80% to 90%.

The combination of E2 and E3 appears to convey safety benefits that the sole use of E2 does not. Binding to ERβ affects not only ERβ but also the expression of ERα. E3 binding with ERβ may antagonize the effect seen with E2’s binding to ERα, which is regarded as a protective effect in many disease states, cancers, and mortality.

While the research provides positive information, there are no clinical studies showing safety benefits in humans. The use of E3 in cancer treatment has not been proven, and support for it is scarce, however, the overwhelming evidence regarding ERβ, E3, and breast cancer suggests a protective mechanism in breast cancer.

The scientific basis for the therapeutic application of compounds is increasingly sound. Rather than making copies of commercial topical E2 products, United States Pharmacopeia-grade active pharmaceutical ingredients, quality topical bases, and accurate dosing devices can be used to prepare compounded estrogen preparations that take into account the nuances of E3 and ERβ.

The continuing research into ERβ and the use of E3 is necessary to determine the full potential of these compounds.

Testosterone – A Potential Hormone Replacement Therapy Most Often Overlooked

Compounding pharmacists also have a unique and valuable ability to prepare suitable testosterone therapies for women.

Testosterone is a crucial hormone for both men and women, yet its potential as a hormone replacement therapy for women is often overlooked.

While there is a considerable amount of clinical information on the subject, there is no commercial product that would drive more interest and publicity.

Studies show total and free testosterone levels decline with age in premenopausal women, with women in their 40s having half the circulating levels of women in their 20s. This suggests some symptoms may be related to testosterone decline, which precedes that of both progesterone and E2, and experts advise testosterone testing for women who are not yet menopausal.

Clinical studies have also provided valuable information on the effects of testosterone therapy on women. Testosterone therapy shows to improve well-being, mood, and sexual function in premenopausal women with low libido and low testosterone levels. It has also been shown to improve sexual desire, arousal, orgasm frequency, pleasure, and overall satisfaction, while decreasing distress associated with Female Sexual Dysfunction (FSD).

In postmenopausal women, androgens can positively influence the quality of life in the short term. There have been reports of improved libido and mood, and reduced hot flashes. The impact of androgens in the long term seems positive as well.

Compounding pharmacists can prepare accurate, gender-specific dosing, in topical and sublingual/buccal dosage forms, and dispense in appropriate devices, on the prescriber's order, when testosterone levels are shown to be low.

A great deal has been learned over the years about hormones and the value of HRT, and compounding pharmacists are eager to serve the needs of physicians and patients with this knowledge. Clinical science continues to be explored, and new information is regularly released so experts can continually grow.

This article is based upon an International Journal of Pharmaceutical Compounding journal entry by Bruce Biundo, RPh, FACA. Biundo a pharmacist consultant with the Professional Compounding Centers of America, Houston, Texas.

Where Does Your Facility Stand?

If you’re looking to become compliant with the new USP requirements or if you wonder how you measure up, let consultants at Restore Health Consulting LLC perform a USP 795 or 797 gap analysis to assess your pharmacy or hospital compliance status against the new minimum standards and lead remediation planning if needed.

Resources

ESTABLISHING A RATIONALE FOR COMPOUNDING - Hormone Replacement Therapy

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