Why most peptide studies excluded women

For most of the twentieth century, women of reproductive age were systematically excluded from early-phase clinical trials. The reasons were partly historical, partly regulatory, and partly a misplaced belief that hormonal cycles introduced too much variability to be worth studying. The result is a research base — including much of the foundational peptide literature — built primarily on male physiology.

After the thalidomide tragedy of the early 1960s, the FDA issued 1977 guidance recommending that women of childbearing potential be excluded from Phase I and early Phase II trials. The intent was protective, but the practical effect was that a generation of drugs was tested almost entirely in men. Dosing, side-effect profiles, and pharmacokinetic models were all built on male data and then extrapolated to women.

It took until 1993 for the NIH Revitalization Act to require women and minorities to be included in NIH-funded clinical research, with cost no longer accepted as a justification for exclusion. The FDA reversed its 1977 guidance the same year. Even so, enrollment lagged behind policy for decades, and many earlier studies were never repeated.

A great deal of the early peptide literature — growth hormone secretagogues, melanocortin agonists, GHRH analogs — was developed when male-only or male-dominated cohorts were the norm. That does not invalidate the chemistry or the receptor biology, but it does mean that dose-response, hormonal interactions, and sex-specific endpoints were often not characterized.

More recent trials have begun to close the gap. Bremelanotide (PT-141) was developed and approved specifically for premenopausal women with hypoactive sexual desire disorder, with the RECONNECT Phase III program enrolling more than 1,200 women. Kisspeptin has been studied in women with hypothalamic amenorrhea and in IVF protocols. But across the broader peptide field, women-specific data is still patchier than the male-derived literature.

The NIH Office of Research on Women's Health, established in 1990, now coordinates a portfolio specifically focused on sex as a biological variable. Since 2016, NIH-funded preclinical research has been required to consider sex as a biological variable in study design — meaning new peptide work increasingly includes both male and female animal models from the start.

The practical takeaway for anyone reading peptide literature: check the sex composition of the cohort before assuming the result generalizes. A finding from a male-only study is a hypothesis for women, not a conclusion about them.