Young, R. L., Goldzieher, J. W., & Elkind-Hirsch, K. E. (1987). The endocrine effects of spironolactone used as an antiandrogen. Fertility and Sterility, 48(2), 223-228. https://doi.org/10.1016/s0015-0282(16)59346-7
Young RL, Goldzieher JW, Elkind-Hirsch KE. The endocrine effects of spironolactone used as an antiandrogen. Fertil Steril. 1987;48(2):223-228. doi:10.1016/s0015-0282(16)59346-7
Young, Ronald L., et al. "The endocrine effects of spironolactone used as an antiandrogen." Fertility and Sterility, vol. 48, no. 2, 1987, pp. 223-228.
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Spironolactone changed androgen levels unevenly between women
Spironolactone changed androgen hormone levels very differently between the women studied, a 1987 report found. It followed 8 women without ovaries and 16 women with hirsutism. Testosterone fell further in 7 out of 16 women with hirsutism when spironolactone was added.
Key Findings
In 8 women without ovaries who took estrogen replacement, responses to 4 weeks of spironolactone varied greatly. DHEAS fell in four women and stayed stable or rose in the other four.
In the 16 women with idiopathic hirsutism, adding spironolactone to dexamethasone for 4 weeks had virtually no effect on DHEAS (P > 0.05).
Testosterone showed a further fall in 7 of 16 women after spironolactone was added (P > 0.05). The 7 included the women whose testosterone stayed above normal on dexamethasone.
After spironolactone was stopped, women with higher testosterone showed a rebound, except in 2 instances where a small further drop occurred.
In the women with hirsutism, androstenedione responses to added spironolactone were inconsistent. Levels fell substantially in four women, rose definitely in four, and changed only slightly in the others (P > 0.05).
Interpretation
This 1987 study is a small hormone experiment with no placebo group. Each woman's later samples were compared with her own earlier ones. The women were 25 to 60 years old (8 without ovaries) and 18 to 39 years old (16 with hirsutism). The authors inferred an ovarian effect on testosterone by assuming that dexamethasone had fully suppressed adrenal production. The further fall in testosterone with spironolactone was not statistically significant. The study reports blood hormone levels and no hair growth or acne outcomes. The authors suggest that blocking the androgen receptor may matter more clinically than the hormone changes.
RRM Context
Restorative reproductive medicine looks for the cause of excess androgen before choosing a medication. The authors note that vein catheterization is the only definitive way to establish the cause. It was not medically justified in these 16 women with idiopathic hirsutism. Hormone responses to spironolactone ranged from falls to rises. The variation shows how much one drug's effect on androgen levels can differ among women.
Our editorial summary of this paper, not the article's abstract.
Abstract
Eight castrate, estrogen-replaced women were given 200 mg spironolactone daily for 4 weeks. The response of plasma dehydroepiandrosterone sulfate (DHEAS), testosterone (T), and androstenedione (delta 4A), all indicators of adrenal C19-steroid production, varied greatly among individuals. Sixteen women with idiopathic hirsutism were given night-time dexamethasone (DEX) and then superimposed spironolactone for 4 weeks, followed by DEX without spironolactone for an additional 4 weeks. As expected, DHEAS, T, and delta 4A declined on DEX treatment. On addition of spironolactone, there was little further change in DHEAS, while plasma T declined in 7 of 16 women, including all those whose T level had remained elevated despite DEX treatment; most values rebounded when spironolactone was discontinued. The authors conclude from intact DEX-suppressed women that ovarian T, especially when increased, is frequently lowered by spironolactone. Thus, both adrenal and ovarian androgen production (as measured by prevailing plasma levels) may be diminished by this agent. These highly variable effects on androgen production are unlikely to account for the consistent antiandrogenic effects reported clinically.
