The History of Bioidentical Hormones in Medicine

If you’ve ever felt dismissed by a doctor when you described your hormone-related symptoms — the fatigue, the brain fog, the sleepless nights — you’re not alone. And you may be surprised to learn that the history of bioidentical hormones stretches back nearly a century, long before the term “BHRT” ever appeared in a wellness magazine. Understanding where bioidentical hormone therapy came from helps explain why it works the way it does, why it’s been so controversial, and why so many patients and providers are returning to it now.

In this post, we’ll walk through the full bioidentical hormone therapy history — from the early laboratory discoveries of the 1920s and 1930s, through the synthetic hormone era of the mid-20th century, to the watershed moment of the 2002 Women’s Health Initiative and the modern resurgence of interest in hormones that mirror the body’s own chemistry. Whether you’re new to this topic or deepening your understanding, this timeline will give you the context you need.

The Early Science: Discovering Hormones in the First Place

To understand the history of bioidentical hormones, you have to start even before the word “hormone” was widely used. In the late 19th century, scientists began to suspect that the ovaries and testes produced chemical messengers that regulated far more than reproduction. By 1905, British physiologist Ernest Starling had coined the word “hormone” — from the Greek word meaning “to set in motion” — and a new field of medicine was born.

The 1920s and 1930s were a golden era of hormonal discovery. In 1929, American biochemist Edward Doisy isolated estrone, one of the three primary estrogens, from the urine of pregnant women. Shortly after, German chemist Adolf Butenandt independently isolated estrone and later went on to isolate androstenone, a precursor to testosterone. Both men received Nobel Prizes for their work. By 1935, scientists had also isolated and characterized progesterone, the hormone that plays a central role in the menstrual cycle and pregnancy.

Critically, what these researchers isolated were molecules that were chemically identical to what the human body produced naturally. In other words, the earliest hormones studied in clinical science were, by modern definition, bioidentical. The path away from that natural chemistry — and the eventual return to it — would unfold over the following decades.

The Synthetic Detour: Convenient Chemistry, Unintended Consequences

By the 1940s and 1950s, pharmaceutical companies recognized the enormous commercial potential of hormone therapy. But there was a significant problem: naturally derived bioidentical hormones couldn’t be easily patented. A molecule that exists in nature is, by definition, not a novel invention. To build a profitable and proprietary drug, manufacturers needed to alter the molecular structure just enough to secure a patent.

This commercial pressure gave rise to a generation of synthetic and semi-synthetic hormones. Medroxyprogesterone acetate (MPA), sold under brand names like Provera, became the standard progestogen used in hormone replacement therapy — even though its molecular structure differs meaningfully from the body’s own progesterone. Similarly, conjugated equine estrogens (CEE), derived from the urine of pregnant mares and sold as Premarin, became the dominant estrogen therapy, despite containing equine estrogens not native to the human body.

These products were approved by the FDA, backed by pharmaceutical marketing, and prescribed widely for decades. By the 1990s, hormone replacement therapy had become one of the most prescribed drug regimens in the United States, with many physicians recommending it not just for symptom relief but as a long-term strategy for heart health and longevity.

Few stopped to ask what the difference between synthetic and bioidentical actually meant — until the research caught up. To explore how these two approaches compare on a clinical level, see our in-depth guide on BHRT vs. Conventional HRT: What’s the Difference?.

The 1970s–1990s: Compounding, Pioneers, and a Growing Countermovement

Even as synthetic hormones dominated mainstream medicine, a small but growing group of physicians and researchers were working with a different philosophy. Throughout the 1970s and 1980s, a handful of forward-thinking clinicians began exploring whether hormones identical to those the body produced could offer relief with fewer drawbacks.

Compounding pharmacies — licensed pharmacies that custom-mix medications to a prescriber’s specifications — became key players in this movement. Because they were not manufacturing drugs for mass distribution, compounding pharmacies could legally prepare formulations using bioidentical hormones like estradiol, estriol, and micronized progesterone, tailored to individual patients’ needs.

French endocrinologist Dr. Henri Labbé and researchers in Europe had long used natural progesterone and estradiol in clinical settings. In the United States, practitioners like Dr. Jonathan Wright became well-known for advocating for estriol — the weakest of the three main estrogens — and for personalized hormone protocols. Dr. John Lee, an American physician, became a prominent voice for natural progesterone, publishing widely read books in the 1990s that brought the concept of bioidentical progesterone to a mainstream audience.

This era also saw the development of the first FDA-approved bioidentical products. Estradiol patches received FDA approval in the mid-1980s, marking a significant milestone in the BHRT history timeline. Micronized progesterone (Prometrium) received FDA approval in 1998. The infrastructure for a more evidence-based bioidentical approach was slowly being built, even as most mainstream medicine remained committed to synthetic formulations.

The 2002 Turning Point: WHI and the Reckoning

No single event did more to reshape the landscape of hormone therapy — and to accelerate interest in the history of bioidentical hormones — than the publication of the Women’s Health Initiative (WHI) study results in July 2002.

The WHI was a massive, federally funded clinical trial that had enrolled over 160,000 postmenopausal women to study the long-term effects of hormone therapy, among other interventions. The arm of the trial using combined estrogen-plus-progestin therapy (specifically, Premarin plus Provera) was halted early when researchers found statistically significant increases in breast cancer, heart attack, stroke, and blood clots among participants.

The publication sent shockwaves through the medical community and the popular press. Almost overnight, millions of women stopped their hormone therapy. Physicians who had been confidently prescribing HRT for decades suddenly felt uncertain. Prescriptions for Premarin and Provera dropped by more than 50 percent in the following years.

But here’s what the headlines largely missed: the WHI studied specific synthetic hormones — not bioidentical estradiol, not micronized progesterone. Many researchers and clinicians argued that the risks identified in the WHI could not and should not be extrapolated to bioidentical formulations. Subsequent research, including analyses published in journals such as Climacteric and Maturitas, began examining whether bioidentical progesterone carried the same breast cancer signal as MPA. The evidence suggested it might not. For a deeper look at the studies that followed, see The Research Behind BHRT: Key Studies Explained.

The Modern Era: Personalization, Evidence, and Mainstream Recognition

In the years following the WHI, interest in bioidentical hormone therapy grew substantially — both among patients looking for alternatives and among researchers willing to study them. The 2000s and 2010s saw an explosion in BHRT-focused clinics, functional medicine practitioners, and online resources devoted to patient education.

Several important developments defined this modern phase of the hormone therapy timeline:

• FDA approval of additional bioidentical products: Beyond estradiol patches and Prometrium, the FDA approved multiple new bioidentical estradiol formulations including gels (EstroGel, Divigel), sprays (Evamist), and vaginal inserts. These FDA-approved options gave patients and physicians access to bioidentical hormones through conventional pharmaceutical channels.

• Growing research on transdermal delivery: Studies began to highlight that transdermal (through-the-skin) estradiol delivery may carry a lower clotting risk than oral estrogens, because it bypasses first-pass liver metabolism. This became an important clinical consideration for providers selecting delivery methods.

• The Endocrine Society and professional bodies weigh in: While major medical societies have remained cautious about compounded BHRT, the conversation has evolved. The Endocrine Society has published position statements distinguishing between FDA-approved bioidentical hormones and compounded preparations, encouraging more nuanced clinical discussion.

• Telehealth expands access: The rise of telemedicine in the 2010s and especially after 2020 made it significantly easier for patients to connect with BHRT-knowledgeable providers, regardless of geography.

For those just entering this space, our foundational guide — What Is BHRT? A Complete Beginner’s Guide — offers a clear overview of how bioidentical hormones work and what the treatment process looks like today.

BHRT History at a Glance: A Timeline

Year	Milestone
1905	Term “hormone” coined by Ernest Starling
1929	Estrone isolated by Edward Doisy
1935	Progesterone isolated and characterized
1941	Premarin (conjugated equine estrogens) receives FDA approval
1960s–70s	Progestins like MPA become standard in HRT protocols
Mid-1980s	FDA approves first estradiol transdermal patch
1990s	Dr. John Lee and others popularize natural progesterone
1998	FDA approves micronized progesterone (Prometrium)
2002	WHI study halted; synthetic HRT risks publicized worldwide
2000s–2010s	BHRT-focused clinical practices expand rapidly
2020s	Telehealth broadens patient access to BHRT providers

Frequently Asked Questions

When were bioidentical hormones first used in medicine?

Bioidentical hormones were first used clinically in the 1930s, when scientists isolated and synthesized estradiol and progesterone from natural sources. Early pioneers like Edward Doisy and Adolf Butenandt laid the biochemical groundwork. However, widespread clinical use of bioidentical estradiol and progesterone as we know it today didn’t gain meaningful traction until the 1980s and 1990s, when compounding pharmacies began creating individualized formulations and the first FDA-approved bioidentical estradiol patches entered the market.

What is the difference between bioidentical and synthetic hormones historically?

Historically, the distinction comes down to molecular structure. Bioidentical hormones are chemically identical to the hormones the human body naturally produces. Synthetic hormones, such as medroxyprogesterone acetate used in conventional HRT, were designed to be patentable and have a different molecular structure. This difference became clinically significant after the 2002 Women’s Health Initiative study raised safety concerns specifically about synthetic hormone formulations, prompting researchers to ask whether the same risks applied to bioidentical alternatives.

How did the Women’s Health Initiative study affect bioidentical hormone therapy?

The 2002 Women’s Health Initiative (WHI) study dramatically reshaped hormone therapy. The trial, which used synthetic conjugated equine estrogens and medroxyprogesterone acetate, reported elevated risks of breast cancer and cardiovascular events. This caused millions of women to stop all hormone therapy — but it also accelerated interest in bioidentical alternatives, which many providers and researchers argued were not studied in the WHI and may carry a different risk profile. The WHI effectively became a catalyst for the modern BHRT movement.

Is bioidentical hormone therapy FDA-approved?

Some bioidentical hormones are FDA-approved, including estradiol patches, gels, and micronized progesterone (sold as Prometrium). However, many BHRT formulations are compounded — custom-mixed by a licensed pharmacy — and are not individually FDA-approved, though the active ingredients themselves may be. The FDA regulates compounding pharmacies under different standards than mass-manufactured drugs. Patients should discuss both FDA-approved bioidentical options and compounded formulations with a knowledgeable, qualified healthcare provider.

Ready to Explore BHRT?

Understanding the history of bioidentical hormones is just the first step. If you’re experiencing symptoms that may be related to hormonal changes — fatigue, mood shifts, weight changes, sleep disruption, or low libido — getting clear on where you stand is the natural next move. Start with our free Hormone Symptom Checklist at /tools/hormone-symptom-checker/, a quick, practical tool to help you identify and articulate your symptoms before speaking with a provider. And for ongoing education, research summaries, and patient stories delivered straight to your inbox, subscribe to our free weekly newsletter at /#newsletter. You deserve answers — and you deserve care that takes your symptoms seriously.

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The content on this site is for educational purposes only and is not intended as medical advice. Always consult a qualified healthcare provider before starting, changing, or stopping any hormone therapy. Individual results vary.