Zimmerman · Human reproduction update 2014 · systematic review and meta-analysis · n=42 studies (1495 participants)

The effect of combined oral contraception on testosterone levels in healthy women: a systematic review and meta-analysis.

Cited 327 times in the scientific literature.

Level 1 - systematic review of randomized trials

Systematic review and meta-analysis of experimental studies.

PubMed 24082040 · doi:10.1093/humupd/dmt038 · record verified 2026-08-29

What was done

A systematic review and random-effects meta-analysis evaluated the effects of combined oral contraceptives (COCs) on total testosterone (T), free T, and sex hormone-binding globulin (SHBG) in healthy women. Searches across MEDLINE, EMBASE, and Cochrane Central covered studies up to July 2012. Subgroup analyses evaluated the impact of estrogen dose (20–25 µg vs. 30–35 µg ethinylestradiol [EE]), progestin type, and assay methods.

What was found

Across 42 experimental studies (1,495 healthy women aged 18–40), COC use significantly decreased total T (mean difference [MD] -0.49 nmol/L, 95% CI -0.55 to -0.42; P < 0.001) and free T (relative change 0.39, 95% CI 0.35 to 0.43; P < 0.001, representing a mean decrease of 61%). SHBG levels increased significantly (MD 99.08 nmol/L, 95% CI 86.43 to 111.73; P < 0.001). Total and free T reductions did not differ by EE dose or progestin type, but SHBG increases were significantly smaller with 20–25 µg EE and second-generation progestins.

Why it matters

This review quantifies the substantial suppression of circulating androgens caused by COCs, showing that free testosterone falls by more than half primarily driven by large increases in SHBG across all common formulations.

Limits

Half of the included studies (21 of 42) were non-comparative experimental designs rather than randomized controlled trials. The meta-analysis was restricted to biochemical measurements in healthy women aged 18–40, and the abstract notes that clinical implications (such as impacts on sexual function or mood) were not evaluated.

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