Serum androgen profiles in women with premature ovarian insufficiency: a systematic review and meta-analysis

Abstract

Objective: This meta-analysis aims to investigate serum androgen profiles (testosterone, dehydroepiandrosterone sulfate, androstenedione, and sex hormone-binding globulin) in women with premature ovarian failure and to establish if there is evidence of diminished androgen levels in these women.

Methods: Various Internet sources of PubMed, Cochrane library, and Medline were searched systematically until February, 2018. Out of a pool of 2,461 studies, after applying the inclusion/exclusion criterion, 14, 8, 10, and 9 studies were chosen for testosterone, dehydroepiandrosterone sulfate, androstenedione, and sex hormone-binding globulin, respectively, for this meta-analysis. The effect measure was the standardized mean difference with 95% confidence interval (95% CI) in a random-effects model.

Results: The testosterone concentrations in premature ovarian insufficiency were compared with fertile controls: stamdard mean difference (IV, random, 95% CI) -0.73 [-0.99, -0.46], P value < 0.05. The dehydroepiandrosterone sulfate concentrations in premature ovarian insufficiency compared to fertile controls: standard mean difference (IV, random, 95% CI) -0.65 [-0.92, -0.37], P value < 0.05. Androstenedione in premature ovarian insufficiency were compared with fertile controls: standard mean difference (IV, random, 95% CI) -1.09 [-1.71, -0.48], P value < 0.05. Sex hormone-binding globulin levels did not show statistical significance. The dehydroepiandrosterone sulfate levels were reduced in premature ovarian insufficiency cases, but still showed a higher level than in postmenopausal women.

Conclusions: Women with premature ovarian insufficiency are at risk for decreased concentrations of testosterone, dehydroepiandrosterone sulfate, and androstenedione. Dehydroepiandrosterone sulfate levels were more reduced in postmenopausal controls when compared with premature ovarian insufficiency cases.

FIG. 1

Search strategy, PRISMA flow chart for meta-analysis on total androgen concentrations.

FIG. 2

Forest plot for meta-analysis of 14 comparative studies on total testosterone concentrations in women with POI/POF compared with fertile controls. Squares represent effect of each study, and the diamond represents the overall effect of the study at 95% confidence intervals. The values to the left of the solid line indicate SMD less than 1, decreased concentrations in POI/POF group. The values to the right of the solid line indicate SMD greater than 1, increased concentrations in POF/POI when compared to the control group. POF, primary ovarian failure; POI, premature ovarian insufficiency; SMD, standardized mean difference.

FIG. 3

Sensitivity analysis for total testosterone concentrations in women with POI/POF compared with fertile controls. Four studies (n = 615) that scored >6 on the Newcastle-Ottawa Scale, considered as the best quality studies, were chosen out of the 14 studies. POF, primary ovarian failure; POI, premature ovarian insufficiency.

FIG. 4

Forest plot for meta-analysis of eight comparative studies on DHEA-S concentrations in women with POI/POF compared with fertile controls. Squares represent effect of each study, and the diamond represents the overall effect of the study at 95% confidence intervals. The values to the left of the solid line indicate SMD less than 1, decreased concentrations in POI/POF group. The values to the right of the solid line indicate SMD greater than 1, increased concentrations in POF/POI compared to the control group. DHEA-S, dehydroepiandrosterone sulfate; POF, primary ovarian failure; POI, premature ovarian insufficiency; SMD, standardized mean difference.

FIG. 5

Subgroup analysis for DHEA-S concentrations in women with POI/POF compared with postmenopausal controls (n = 465), indicating that the DHEA-S levels are much reduced in POI/POF controls, but still show a higher concentration than DHEA-S in postmenopausal women. DHEA-S, dehydroepiandrosterone sulfate; POF, primary ovarian failure; POI, premature ovarian insufficiency.

FIG. 6

Sensitivity analysis for DHEA-S concentrations in women with POI/POF compared with fertile controls. Three studies (n = 210) that scored >6 on the Newcastle-Ottawa Scale, considered as the best quality studies, were chosen out of the eight studies. DHEA-S, dehydroepiandrosterone sulfate; POF, primary ovarian failure; POI, premature ovarian insufficiency.

FIG. 7

Forest plot for meta-analysis of 10 comparative studies androstenedione concentrations in women with POI/POF compared with fertile controls. The values to the left of the solid line indicate SMD less than 1, decreased concentrations in POI/POF group. The values to the right of the solid line indicate SMD greater than 1, increased concentrations in POF/POI when compared to the control group. POF, primary ovarian failure; POI, premature ovarian insufficiency; SMD, standardized mean difference.

FIG. 8

Sensitivity analysis for androstenedione concentrations in women with POI/POF compared with fertile controls. Three studies (n = 463) that scored >6 on the Newcastle-Ottawa Scale, considered as the best quality studies, were chosen out of the 10 studies. POF, primary ovarian failure; POI, premature ovarian insufficiency.