.webp)
In this article
Meet the Experts
Nicole Shin, WHNP-BC, is a board-certified women’s health nurse practitioner with Paloma Health. Nicole has over a decade of experience specializing in thyroid health, menopause, and hormone management.
Julio Baute, MD, is a physician with Invigor Medical, specializing in patient communication, health coaching, and digital health tools, focusing on sharing trustworthy, evidence-based information on wellness, obesity care, and preventive health.
If you’re riding the hormonal rollercoaster of perimenopause or menopause, you’ve likely heard about bioidentical hormone replacement therapy (BHRT). Promoted as a more natural or safer alternative to conventional hormone replacement therapy (HRT) for menopausal symptoms, BHRT has become increasingly popular among women seeking relief from hot flashes, night sweats, mood swings, weight gain, brain fog, and vaginal dryness. Celebrities and wellness influencers have praised BHRT, often claiming it is the best way to balance hormones and “turn back the clock.”
But what does the science actually say?
Is BHRT safer? Is it more effective? And what should you know before choosing bioidentical hormones over conventional options?
Let’s take a look at the research and separate the hype from the evidence so that you can make an informed decision about your hormone health.
Synthetic hormones include the traditional conjugated equine estrogens (CEE) and synthetic progestins, such as medroxyprogesterone acetate (MPA), found in popular branded HRT drugs like Premarin, Prempro, and Provera.
In contrast, bioidentical hormones are compounds that are chemically identical to those produced by the human body, most commonly estradiol (a form of estrogen) and progesterone.
There are two different types of bioidentical hormones: FDA-approved and manufactured hormones, and compounded hormones.
FDA-approved bioidentical hormones
The FDA has approved several bioidentical hormone products, which have undergone official testing for safety and effectiveness.
Estrogen
- Oral tablet: Estrace, generic estradiol
- Patch: Climara, Alora, Vivelle, Vivelle-Dot, Minivelle, Menostar, Esclim, Estraderm, generic patches
- Gel: Divigel, EstroGel, Elestrin
- Spray: Evamist
- Cream: Estrace, Estrasorb, generic creams
- Vaginal ring: Estring, Femring
- Vaginal tablet: Vagifem, Yuvafem, Imvexxy
- Injection: Depo-Estradiol
Progesterone
- Oral capsule: Prometrium, generic micronized progesterone
- Vaginal gel: Crinone
- Vaginal insert: Endometrin
Combination products
- Oral capsule: Bijuva (estradiol/progesterone)
Compounded bioidentical hormones
Compounding pharmacies can create customized mixes of hormones and dosages that are not found in standard, manufactured products. The delivery forms for compounded bioidentical hormones include:
- Oral capsules or pills
- Sublingual tablets, troches, and lozenges
- Topical creams and gels
- Transdermal patches
- Pellet implants
- Injectables
- Vaginal or rectal suppositories
Bioidentical hormones differ from synthetic hormones in several ways.
Molecular structure
Bioidentical hormones are structurally identical to the hormones produced by the human body. Synthetic hormones have a similar but not identical structure to natural hormones, and can have different effects on the body.
Origin
Bioidentical hormones are typically derived from plant sources such as yams or soy, and then chemically modified to match human hormones. Synthetic hormones are often derived from animal sources (e.g., conjugated equine estrogens from horse urine) or are entirely synthesized in laboratories.
Effectiveness
One area where there is no difference is effectiveness. According to Dr. Julio Baute, “Both control hot flashes, improve sleep, and protect the bone. The key difference is that bioidentical estradiol and micronized progesterone match the body’s own hormones molecule-for-molecule.”
Clinical trials and observational studies show that both bioidentical estradiol and progesterone are as effective as synthetic versions for menopause symptoms such as:
- Reducing hot flashes and night sweats
- Improving vaginal dryness and sexual function
- Supporting mood and sleep
- Protecting bone health and preventing bone loss
Studies do suggest that transdermal estradiol can improve mood and reduce depressive symptoms, especially in perimenopausal women. Bioidentical progesterone may have calming effects and improve sleep, whereas synthetic progestins can cause irritability in some women.
Patient satisfaction
Patients also report greater satisfaction with bioidentical HRT compared to synthetic HRT. A study published in the journal Menopause found that women using bioidentical transdermal estradiol and oral micronized progesterone hormonal therapy had better quality-of-life outcomes and sleep improvements compared to those using synthetic conventional HRT.
A critical difference between bioidentical and synthetic hormones is that some studies and clinical observations suggest that bioidentical hormones may be associated with fewer risks and side effects compared to synthetic hormones. These safety findings also form the basis for the preference some practitioners have for prescribing bioidentical hormones instead of synthetic ones.
Specifically, research shows that bioidentical transdermal estradiol and micronized progesterone are associated with lower risks compared to synthetic hormone formulations in several key areas.
Blood clots and heart risk
- FDA-approved bioidentical estradiol—especially in transdermal form—is associated with lower risks of blood clots, stroke, and heart problems, compared to oral synthetic estrogen. Transdermal estrogen bypasses the liver, avoiding some metabolic changes that can increase clotting factors.
- Transdermal estradiol does not increase stroke risk, but oral (pill) estrogen can, especially at high doses.
- Synthetic progestins (like medroxyprogesterone/MPA) have been linked to adverse cardiovascular effects, while bioidentical micronized progesterone may avoid some of these risks.
Breast cancer
- Multiple reviews and observational studies indicate that bioidentical micronized progesterone is associated with a lower risk of breast cancer compared to synthetic progestins such as MPA. For example, a 2009 review concluded: “Both physiological and clinical data have indicated that progesterone is associated with a diminished risk for breast cancer, compared with the increased risk associated with synthetic progestins.”
- An observational study cited in a 2011 review found a decreased risk of invasive breast cancer with the use of a combination of micronized progesterone and estrogen compared to synthetic progestogens. However, the authors caution that more research is needed to confirm long-term safety.
Overall, research has concluded that transdermal estradiol and micronized progesterone are generally safer than synthetic hormone versions, especially when it comes to blood clots, heart disease, and breast cancer.
It also appears that the route of administration for hormones matters. Transdermal forms of estradiol appear to carry a lower risk of blood clots and stroke than oral forms, whether bioidentical or synthetic.
A difference of opinion
Surprisingly, having a preference for bioidentical hormones is still controversial among some healthcare practitioners. The FDA and leading medical organizations claim that bioidentical hormones are not inherently safer simply because they are “natural” or “identical” to those produced by the body. At the same time, they agree that FDA-approved bioidentical hormones – when used appropriately – are safe and effective for menopausal symptom relief.
But there is a resistance to making any claims that bioidentical HRT is safer or more effective than FDA-approved hormone replacement therapies like conjugated estrogens and synthetic progestins. Most medical organizations, such as the Endocrine Society, ACOG, and the Mayo Clinic, maintain that there is not enough evidence to support such claims, although more are now acknowledging that some of the observational data is promising and are calling for further research.
The issue of compounded bioidentical hormones is the most controversial aspect of BHRT. The conventional medical establishment strongly recommends that patients requiring hormone replacement be prescribed synthetic or FDA-approved manufactured bioidentical hormones and avoid compounded BHRT.
Here are several concerns commonly leveled against compounded BHRT by organizations, including the North American Menopause Society and the Endocrine Society:
- These medications are not FDA-approved.
- They lack standardization.
- The efficacy of these drugs is not well-established.
- They’re not subject to the same quality controls as FDA-approved medications.
- They lack robust safety data.
- The variability in hormone content and absorption can lead to under- or overdosing, and there is no guarantee of consistent potency.
- Because of the lack of safety data and quality controls, compounded bioidentical hormones should be used with caution and only in rare cases where a patient can’t use the standard products and compoounded forms are deemed “medically necessary.”
According to Paloma women’s health nurse practitioner Nicole Shin, “Bioidentical hormones are similar to what your body produces. And there are also compounded medications. Each individual is different, and their needs may be different as well.”
The compounding pharmacy industry’s response
Some physicians and the compounding pharmacy industry respond to criticisms about compounded hormone replacement therapy (HRT) by emphasizing the essential role of compounding in meeting patient-specific needs, defending the safety of their practices when proper standards are followed, and advocating for state-level (rather than federal) regulation.
Here’s a breakdown of the arguments in favor of the availability of compounded BHRT:
- Compounding is a necessary aspect of health care. It allows for customized medications when commercially available products do not meet patients’ needs (for example, in the case of patient allergies, unique dosing requirements, or drug shortages).
- Compounded hormones are particularly vital during drug shortages and ensure that patients continue to receive needed therapies.
- Compounding pharmacies are already regulated by state pharmacy boards, which oversee their practices and ensure quality and safety.
- Voluntary accreditation programs, such as the Pharmacy Compounding Accreditation Board (PCAB), and compliance with standards set by the US Pharmacopeial Convention (USP), are evidence of a commitment to quality and safety.
- While there are isolated quality issues with compounding, they are not representative of the industry as a whole.
- Most adverse events are associated with improper sourcing or non-pharmacy providers of compounded medications, not legitimate, accredited compounding pharmacies.
Guidelines for the best outcomes with compounded BHRT
Here are some guidelines on achieving the best outcome with compounded bioidentical HRT.
- Use compounded HRT only with a valid prescription from a licensed healthcare provider who is knowledgeable about menopause management and hormone therapy.
- Choose a reputable, accredited compounding pharmacy that your healthcare provider recommends
- Select compounding pharmacies that are accredited and that adhere to USP standards. This helps ensure consistent quality and safety of compounded medications. According to Dr. Julio Baute, “The main safeguard is choosing an accredited compounding pharmacy, because, unlike FDA-approved patches or capsules, testing standards can vary from one facility to the next.”
- Confirm that the pharmacy is licensed and regulated by your state board of pharmacy.
- Ask the pharmacy about their quality control procedures, including how they test for potency and purity of compounded medications.
- Report any unusual side effects or lack of symptom relief to your provider promptly, as compounded products can vary in absorption and efficacy.
- Only obtain compounded HRT from legitimate, identifiable pharmacies—not from online sellers, medspas, or providers who do not require a prescription.
Paloma’s Nicole Shin sums up Paloma’s approach: “One size does not fit all. Listening is the most important thing and the key to effective treatment. It’s about working together and using patient-centered care to ensure that we are using the best treatment available, whether it’s bioidentical hormones that are manufactured or through a compounding pharmacy.”
Ultimately, the decision to use bioidentical hormone replacement therapy is a personal one to make with your health care provider. Proponents argue that BHRT may offer a more natural and individualized approach, especially when compounded to match your specific hormonal needs. Supporters claim it can relieve symptoms of menopause and perimenopause—such as hot flashes, mood swings, and low libido—while also potentially improving sleep, bone density, and skin elasticity. Some people report fewer side effects compared to conventional hormone therapy.
Still, it’s important to be aware that BHRT isn’t without controversy. Custom-compounded hormones are not FDA-approved, meaning their safety, consistency, and efficacy may vary. Some medical organizations caution that there’s limited high-quality evidence showing BHRT is safer or more effective than standard hormone therapy. In addition, risks like blood clots, stroke, and certain cancers may still apply, especially with long-term use and/or higher dosages. It’s essential to weigh the potential benefits and risks with a knowledgeable healthcare provider who can help you choose the best treatment approach for you, monitor your hormone levels, and evaluate treatment outcomes.
When done correctly and for the right patients, bioidentical hormone replacement therapy BHRT is a valuable and safe option for patients. For optimal outcomes, Paloma recommends that patients work closely with knowledgeable healthcare providers and use FDA-approved bioidentical hormones or compounded formulations from accredited pharmacies.
Paloma Health members navigating perimenopause and menopause benefit from a convenient and personalized approach to hormone replacement treatment. Through virtual consultations with experienced hormone specialists, Paloma provides comprehensive testing, in-depth symptom analysis, and tailored treatment plans that may include HRT, including branded or compounded bioidentical hormones. With ongoing support and easy access to your care team, Paloma makes it easier to start and manage HRT safely and effectively from the comfort of your home.
Your hormonal health is personal and powerful. Make sure your treatment plan is too. If you’re considering hormone therapy, consider working with a Paloma healthcare provider who understands your full spectrum of options and who can help you create a customized HRT plan that’s best for you and your health.
- Bioidentical hormone replacement therapy (BHRT) uses hormones chemically identical to those your body produces, and is promoted as a more natural alternative to conventional hormone therapy.
- FDA-approved bioidentical hormones (like estradiol and micronized progesterone) are effective and considered safe when used appropriately, with some evidence suggesting fewer risks than synthetic hormones.
- Studies show that transdermal estradiol and oral micronized progesterone may reduce the risks of blood clots, stroke, heart disease, and breast cancer compared to synthetic hormones.
- Patient satisfaction is generally higher with bioidentical HRT, with many women reporting better sleep, mood, and overall quality of life.
- Compounded bioidentical hormones, which are custom-mixed by pharmacies, are more controversial due to a lack of FDA approval, a lack of standardization, and inconsistent safety data.
- Paloma Health recommends working with knowledgeable providers and using FDA-approved or carefully sourced compounded BHRT to ensure safe, personalized treatment.
