DHEA Levels in Transgender Women on Hormone Therapy

observational-study PMID: 36201493

DHEA Levels in Transgender Women on Hormone Therapy

Quick Summary: This study tracked hormone changes in 275 transgender women starting feminizing hormone therapy with estrogen and a testosterone blocker. It found that DHEA—a natural hormone from the adrenal glands—dropped by about 28% in the first year and stayed stable after that. Even after surgery to remove the testes, DHEA levels did not change further, helping doctors understand long-term effects.

What the Research Found

Researchers measured key hormones like testosterone and adrenal androgens (including DHEA and its sulfate form, DHEAS) in transgender women on hormone therapy. Here's what happened in simple terms:

Testosterone Drop: Levels fell sharply by 97% within 3 months of starting therapy and stayed low over time.
DHEA Changes: DHEA decreased by 28% (from about 26.4 to 19 nmol/L) after 1 year, then leveled off. DHEAS, the stored form of DHEA, dropped by 20% in the same period and remained steady.
Other Androgens: Androstenedione (another androgen) fell by 37% early on but didn't change much later.
Surgery Impact: About half the women had gonadectomy (testicle removal) during the study. Stopping the testosterone blocker after surgery didn't affect DHEA, DHEAS, or other hormones compared to those who skipped surgery. This shows adrenal glands keep producing these hormones steadily.

These findings confirm that after the first year, hormone levels stabilize, even post-surgery.

Study Details

Who was studied: 275 transgender women beginning feminizing gender-affirming hormone therapy (GAHT). They were a diverse group, with nearly half undergoing gonadectomy over time.
How long: Follow-ups at 3 months, 12 months, and 2–4 years after starting therapy.
What they took: Daily estradiol (a form of estrogen) and cyproterone acetate (CPA, a medication that blocks testosterone). Exact doses weren't detailed, but CPA was stopped after gonadectomy in those who had it. DHEA was not given as a supplement—it was measured naturally in the blood using precise lab tests.

What This Means For You

If you're a transgender woman on hormone therapy or considering it, this study offers reassuring insights:

Expect a big drop in testosterone right away, which helps with feminization like softer skin and fat redistribution.
DHEA and similar adrenal hormones will decrease in the first year but won't keep falling. This might affect energy, mood, or sex drive—talk to your doctor if you notice changes.
Gonadectomy won't cause extra hormone shifts from the adrenals, so you may not need adjustments to your meds after surgery. It challenges the idea that surgery alone fully controls all androgens.
For overall health, focus on regular blood tests to monitor levels. If symptoms like fatigue persist, they might not be from low DHEA—other factors like estrogen dose or lifestyle could play a role. Always consult a healthcare provider for personalized advice, especially if thinking about DHEA supplements (not studied here).

Study Limitations

This research provides solid data but has some caveats to keep in mind:

It's observational, so it shows patterns but doesn't prove cause-and-effect.
Dosages of estrogen and CPA weren't specified, so results might vary by treatment plan.
It didn't link hormone changes to real-life symptoms, like tiredness or low libido—more studies are needed.
Surgery timing differed among participants, which could influence comparisons.
Follow-up stopped at 4 years, so we don't know about effects beyond that.
No comparison to cisgender women, so it's specific to transgender experiences on this therapy.

Key Findings

This study found that serum DHEA and DHEAS levels in transgender women decreased by 28.0% (-7.4 nmol/L, 95% CI: -9.7 to -5.1) and 20.1% (-1.8 µmol/L, 95% CI: -2.2 to -1.4), respectively, within the first year of feminizing gender-affirming hormone therapy (GAHT) using estradiol and cyproterone acetate (CPA). These reductions plateaued after 12 months, with no further changes observed over 2–4 years. Gonadectomy (performed in 49.5% of participants) did not alter DHEA, DHEAS, or other androgen levels post-GAHT, suggesting adrenal androgen production remains stable after surgical removal of gonads. Testosterone levels dropped sharply within 3 months (97.1% reduction) and remained low throughout the study.

Study Design

This observational cohort study followed 275 transgender women initiating GAHT with estradiol and CPA. Participants were assessed at baseline, 3 months, 12 months, and 2–4 years. Serum androgens (TT, cFT, A4, DHEA, DHEAS) were measured via liquid chromatography tandem mass spectrometry (LC-MS/MS). The study included a mixed cohort of individuals with and without gonadectomy, comparing longitudinal changes between groups.

Dosage & Administration

The study summary does not specify exact estradiol or CPA dosages used in GAHT. However, CPA was discontinued after gonadectomy, which occurred in approximately half the cohort. DHEA was measured as an endogenous biomarker, not administered as a supplement.

Results & Efficacy

Testosterone: TT decreased by 18.4 nmol/L (-97.1%, p < 0.001) within 3 months and remained suppressed.
Adrenal Androgens:
DHEA fell by 7.4 nmol/L (-28.0%) after 1 year (p < 0.001, 95% CI: -9.7 to -5.1).
DHEAS decreased by 1.8 µmol/L (-20.1%) after 1 year (p < 0.001, 95% CI: -2.2 to -1.4).
Gonadectomy Impact: No statistically significant differences in TT, cFT, DHEA, DHEAS, or A4 were observed between those who underwent gonadectomy and those who did not (p > 0.05).

Limitations

Observational design limits causal inference.
CPA dosage details and estradiol formulations were unspecified.
Adrenal androgen changes were not correlated with clinical symptoms (e.g., fatigue, libido).
Gonadectomy timing varied (not standardized), potentially confounding post-surgery comparisons.
Follow-up duration (up to 4 years) may be insufficient to assess long-term androgen dynamics.
No control group of cisgender women for baseline comparisons.

Clinical Relevance

For transgender women, these findings suggest that adrenal androgen suppression occurs early in GAHT and stabilizes after 1 year, with no additional changes post-gonadectomy. This challenges assumptions that surgical removal of gonads further reduces androgen levels. Clinicians should consider non-androgenic factors (e.g., estradiol dosing, individual variability) when addressing symptoms like fatigue or mood changes during GAHT. The data also imply that DHEA supplementation post-gonadectomy may not be necessary to counteract androgen decline, though its role in symptom management remains unstudied here. Further research is needed to link androgen levels to clinical outcomes.

Note: This analysis focuses solely on DHEA/DHEAS outcomes reported in the study. Full details on estradiol/CPA protocols and symptom correlations were not provided in the summary.