When We Ask: Is Follistatin Safe for Women or Trans Individuals on Hormone Therapy?

We must begin by understanding what follistatin is—and then examine the evidence with a critical lens. Follistatin is a glycoprotein, meaning a protein combined with sugar chains, naturally produced in the body. Its primary role is binding to and neutralizing proteins such as myostatin and activin, which normally act to slow down muscle growth or regulate reproductive processes.

*By inhibiting these, follistatin can promote muscle growth and influence reproductive hormone systems (universal background). *

Our interest lies in whether follistatin can be safely used by women or transgender people undergoing hormone therapy—a group whose endocrine (hormonal) balance is already being medically altered.

In a clinical trial involving six adult patients with Becker muscular dystrophy (BMD)—a degenerative muscle disease—researchers delivered a genetic construct of follistatin (FS344) via an adeno-associated virus (AAV1) directly into leg muscles. Over six months to one year, participants walked farther in six-minute tests and showed healthier muscle tissue under microscopic analysis. Notably, no adverse effects were reported, but the trial was limited to a small number of individuals with a specific disease, and muscle—not hormone systems—was the focus.

A parallel primate study in macaques delivered the same construct and observed increased muscle size over 12 weeks and sustained expression up to 15 months. Hormonal measures—such as estrogen, testosterone, and follicle-stimulating hormone (FSH)—remained unchanged, suggesting that reproductive hormonal systems were not overtly affected in these animals. Yet again, this was in healthy primates—not in people undergoing hormonal therapy PMC.

A more recent human Phase I trial assessed safety of an injectable plasmid carrying the FST344 gene in healthy adult volunteers. Participants underwent scans and blood tests before and three months after injection. While detailed results are unpublished, the design highlights caution and monitoring, although the participants were not women on hormone therapy. A related preprint with both sexes reported minimal side effects, some slight increases in LDL (“bad”) cholesterol in a minority, no serious adverse events, and intriguing signals such as reduction in epigenetic biological age—but again, this was not focused on our group of interest.

Turning to women with metabolic and reproductive conditions, a longitudinal study of adolescent girls with polycystic ovary syndrome (PCOS) compared standard oral contraceptives versus insulin-sensitizing treatments over six months. The study revealed that contraceptive use raised serum follistatin levels by 6-fold, which correlated with worsened insulin resistance and increased liver fat—both metabolic risks already relevant to hormone therapy patients.

Why We Should Be Critically Concerned

From these data, several concerns emerge. First, while follistatin gene therapies appear safe in very specific and small populations, no studies have directly tested safety in women undergoing estrogen therapy or transgender individuals. The promising primate data cannot substitute human results in hormone-altered contexts. Second, findings from the PCOS cohort raise red flags: elevated follistatin seems to worsen metabolic markers in young women, which is significant because estrogen therapy can also affect metabolism, and combining that with altered follistatin levels may pose compounded risks.

Third, human trials so far involve short duration, small sample, and different endpoints than reproductive or metabolic outcomes. We lack long-term, large-scale data in the relevant populations.

What We Need to Know, If We Were in That Situation

We would urgently need targeted studies that enroll women and transgender individuals on hormone therapy. These studies should carefully measure not only muscle and strength outcomes but also metabolic health (insulin sensitivity, liver fat), reproductive hormone levels, and safety over extended time. Without such data, any use of follistatin in this context would be speculative and risky.

Thus, the critical conclusion is that we simply do not know—the current science does not address the population we care about. While follistatin shows intriguing potential in muscle disorders and seems safe in certain trials, there is no evidence yet for safety or efficacy in women or trans individuals undergoing hormone therapy. Worse, the rise in insulin resistance seen in PCOS contexts suggests a potential downside that demands caution. Until rigorous targeted research is conducted, follistatin must remain off-limits for that group.

User Experiences: Follistatin Use in Women and Transgender Individuals Undergoing Hormone Therapy

Community discussions on Tressless show that follistatin is generally viewed with curiosity but also with caution, especially for women and transgender individuals undergoing hormone therapy. Users note that while research indicates follistatin’s potential to stimulate hair growth by inhibiting myostatin and modulating activin pathways, there is still little human safety data, particularly for people outside of male-pattern-baldness trials.

Several members reference its inclusion in hair regrowth treatments alongside Wnt signaling activators and growth factors. Reports from a Phase 1 clinical trial indicated the approach was well-tolerated with no adverse effects in male participants, but these results did not address hormone-related contexts, pregnancy risks, or the long-term endocrine impact for women or trans individuals. This gap in evidence is a recurring concern in community threads, with experienced users warning that the interplay between follistatin and hormone therapy is unknown and could theoretically disrupt endocrine balance.

Participants with a background in bodybuilding or peptide use mention follistatin’s popularity in muscle enhancement circles, where it is sometimes used in high, non-physiological doses. They caution that these practices carry risks such as unpredictable hormone signaling effects, especially in bodies already undergoing significant hormonal modulation from estrogen, testosterone, or anti-androgens. The consensus is that without targeted studies in these groups, dosing, safety, and interaction profiles remain speculative.

There is also recognition that while follistatin has shown regenerative and hair follicle–promoting effects in mice and small human trials, the mechanism—blocking activin—plays roles beyond hair growth, including in reproductive tissue function and wound healing. For women and transgender users, the community repeatedly advises that these functions may overlap with hormone therapy targets, making self-experimentation riskier without medical oversight.

In summary, Tressless community voices lean toward cautious optimism: follistatin appears promising as a hair growth adjunct, but the absence of female- or transgender-specific data means it should not be considered a routine or “safe” option without further research and specialist guidance.

References

Khoury, R. H., Wang, Q. F., Crowley, W. F., Hall, J. E., Schneyer, A. L., Toth, T., Midgley Jr, A. R., & Sluss, P. M. (1995, April 1). Serum follistatin levels in women: Evidence against an endocrine function of ovarian follistatin. The Journal of Clinical Endocrinology & Metabolism, 80(4), 1361–1368. Retrieved from https://academic.oup.com/jcem/article/80/4/1361/2650207

Alfano, L. N., Berry, K., Meadows, E., ... Rodino-Klapac, L. R., et al. (2015, January 10). A Phase 1/2a follistatin gene therapy trial for Becker muscular dystrophy. Molecular Therapy. Retrieved from https://pubmed.ncbi.nlm.nih.gov/25322757/

Mendell, J. R., Rodino-Klapac, L. R., et al. (Year unspecified). Function in Becker Muscular Dystrophy Patients Improved With Follistatin Gene Therapy. Muscular Dystrophy News. Retrieved from https://musculardystrophynews.com/news/function-in-becker-muscular-dystrophy-patients-improved-with-follistatin-gene-therapy/

Study in macaques: Injection of AAV1-FS344 into the quadriceps increases muscle mass in cynomolgus macaques. Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC2852878/

Clinical trial NCT06411366: Phase I safety & efficacy of injectable follistatin plasmid gene therapy in humans. Retrieved from https://inclinicaltrials.com/aging/NCT06411366/details/

Minicircle preprint (FST delivery): Plasmid delivery of follistatin gene therapy safely improves body ... Retrieved from https://minicircle.io/wp-content/uploads/2024/04/fstpreprint.pdf

Díaz, M., de Zegher, F., & Ibáñez, L. (2023, February 9). Circulating follistatin concentrations in adolescent PCOS: Divergent effects of randomized treatments. Frontiers in Endocrinology. Retrieved from https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1125569/full

Study on PCOS and metabolic correlations: The concentration of follistatin and activin A in serum... Retrieved from https://www.mdpi.com/2077-0383/13/17/5316

https://reddit.com/r/tressless/comments/16f1m6n/follistatin_thoughts_about_a_potential_treatment/

https://reddit.com/r/tressless/comments/ud92t/injections_of_follistatin_and_growth_factors/

https://reddit.com/r/tressless/comments/27aycv/hair_regrowth_following_a_wnt_and_follistatin/