FTM Evidence Gaps

Why gaps don’t mean “unsafe” or “settled”

Most transmasc testosterone care rests on decades of clinical experience plus cohort studies (studies that follow groups of people over time), not randomized controlled trials (RCTs). There are no RCTs of testosterone in trans populations_{(That I could find)}, for ethical and practical reasons.¹ A gap means “not studied,” not “proven dangerous” and equally not “proven fine.” Where a question below affects you, it’s a conversation to have with a clinician if possible and in writing if helpful.

Information gaps

Low-dose / nonbinary regimens are essentially unstudied. Zero completed randomized trials. The only cohort (Nolan 2024, n=46) tracked doses and levels but not physical outcomes so “low-dose gives the same endpoint, slower” vs “a lesser endpoint” is unresolved on paper. The first RCT that I know of is still recruiting at Austin Health, Melbourne. An NHS England review found zero eligible studies for nonbinary partial masculinization in under-18s.²³⁴ Details: FTM Low-Dose and Nonbinary.

Estradiol(E2) and progesterone(P4): measured, but never linked to outcomes. We know E2 on T settles into the male/early-follicular range (the low level seen early in a menstrual cycle) and P4 collapses to near-zero but no study has ever correlated E2 or P4 levels with bone density, mood, pelvic pain, or any other clinical outcome in transmasc people. Whether aromatized (converted from T) E2 is “enough” for bone, especially after oophorectomy (surgery to remove the ovaries) on a low dose, is assumed but untested.⁵ No guideline recommends routine E2/P4 monitoring, and there’s no evidence base to say whether that’s correct.⁵

A note from Aria

You could help this! When getting your pathology requests ask for both E and prog to be added and keep a log! it could be helpful for future community research <3

Progesterone data is almost nonexistent. Serum (blood) P4 has been reported in only ~4 small studies (largest n=41). P4’s physiological role in transmasc people and bone, mood and/or breast tissue has never been studied at all.⁵

Topical vaginal estrogen has never been studied in transmasc people. It’s the standard offered treatment for atrophy (tissue becoming thinner and drier), and guidelines assert very little is absorbed into the bloodstream but every word of that is extrapolated from postmenopausal cis-women data. No transmasc study of efficacy, absorption, or effect on masculinization exists.⁶ See FTM Periods and Fertility.

No post-top-surgery chest screening protocol. Risk from residual chest tissue is unquantified; whether/when to image (mammography often isn’t technically feasible; ultrasound/MRI is untested here) is unknown. Every guideline says the same thing: no evidence exists. take a family history, report lumps, individualize.⁷⁸

Aging on T has sparse data. Nearly all cohorts have mean ages of 30-40. SOC8 concedes “it is not known if doses of GAHT should be reduced in older TGD people” (GAHT = gender-affirming hormone therapy); one expert-opinion source floats considering stopping around age 50 while SOC8 frames T as lifelong, and is unresolvable with current data.⁸⁹

A note from Aria

Personally I wouldn’t suggest stopping after 50, that sounds absurd.

No validated hematocrit threshold. The Endocrine Society flags hematocrit (the share of your blood made up of red cells) >50% as “very high risk”; the >54% “pause” threshold is imported from cis-men TRT (testosterone replacement therapy) guidance. The authors of the largest erythrocytosis (too many red blood cells) cohort themselves note it’s unknown whether cis-male limits apply to trans men.¹⁰ See FTM Risks and Side Effects.

Cardiovascular hard outcomes: Getahun 2018 (Kaiser) found MI/stroke rates similar across groups, and Dutch mortality data show no excess CV death. Nota 2019 and Alzahrani 2019 found higher MI rates vs cisgender women (not cis men). All observational (watching people rather than testing treatments), few events, poorly adjusted for smoking. Probably no large excess risk vs cis men but “probably” is the operative word.¹¹¹²¹³

Underdosing prevalence Deutsch 2015 (n=31) found ~1/3 of trans men sub-therapeutic (below the level needed for full effects) at 6 months on typical starts, the best direct evidence, and it’s a decade old with 31 people. No large modern quantification by formulation exists, despite it being one of the community’s most consistent grievances.⁹¹⁴

A note from Aria

Scream and shout about under dosing! share information about doctors that don’t provide adequate care or are very slow with dose changes online!!

That shared information is what the community needs in this case, be part of that mutual aid <3

Contraceptive efficacy on T Effectiveness estimates are borrowed from cis-women data. The ovulation rate on T is genuinely unsettled (5% to 36% depending on study and lab test threshold). all we know is it’s not zero.¹⁵

The pregnancy washout question How long before conception T should be stopped (washout = the time T takes to clear your system) is explicitly unknown per both UCSF and SOC8. Similarly, whether long-term T affects egg quality or children conceived afterward: “major gaps in knowledge,” in SOC8’s words.⁸⁹

Pelvic pain Documented at 23-72% depending on the population but etiology (the underlying cause) is unresolved, and no treatment has been tested prospectively (in a planned, forward-looking study).¹⁶

Sexuality, emotion, and “passing” Orientation-change research is two small studies disagreeing with each other; “passing” has essentially no direct research (the 95.5% figure is a 25-person face-photo study); the emotional-flattening/“calmer” experience has one prospective affect (emotion) dataset.¹⁷

A note from Aria

“Passing” is a weird thing, studies around it would be strange and extremely hard to verify without falling into 4trans bait. The biggest thing is passing takes time, time for T to do it’s thing and time for you to learn how you want to express your masculinity. dont rush this, you have time.

Community-grade unknowns. Genital T/DHT (a stronger hormone made from testosterone) cream for bottom growth, minoxidil beard durability after stopping, and gray-market testosterone quality (community lab testing of T is severely lacking) all live here. See FTM Community Knowledge.

What to do with this

Be suspicious of certainty from any source, including professional ones.
Ask “what’s this based on?” a guideline, a cohort, a case report, comunity research, or an indaviduals experince?
Participate if you can. Studies like ENIGI, the Austin low-dose RCT, and community surveys exist because trans people volunteer; recruiting studies are often listed by local gender clinics and research networks. Outside of professional research please share any knowledge or experience with those around you! our biggest strength is comunity.
Screen anyway. Anatomy-based screening and hematocrit monitoring are how you stay safe while population-level answers catch up. see FTM Long-Term Health and FTM Blood Testing.

Want to read the primary literature itself? I upload paper on the Research Papers page, or dive into the footnotes across this site!

The Trans Directory

Explorer

FTM Evidence Gaps

Why gaps don’t mean “unsafe” or “settled”

Information gaps

What to do with this

Further reading

Graph View

Table of Contents

Backlinks

The Trans Directory

Explorer

FTM Evidence Gaps

Why gaps don’t mean “unsafe” or “settled”

Information gaps

What to do with this

Further reading

Footnotes

Graph View

Table of Contents

Backlinks