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An important and to date not clearly resolved question in clinical reproductive medicine has been whether premature loss of ovarian function (e.g. primary ovarian insufficiency (POI) below the age of 40 years) and iatrogenic premature loss of ovarian function (as a result of surgery, gonadotoxic chemotherapy or pelvic irradiation) result in a significant decrease in circulating testosterone concentrations and hence might merit testosterone treatment. Many published studies have included small sample sizes and/or non-uniform control groups. Janse and colleagues [1] have undertaken a systematic review and meta-analysis of the literature and conclude that testosterone levels are lower, though the magnitude of the difference is relatively small. They reviewed 206 articles on POI and 1358 on iatrogenic menopause, of which nine and 17, respectively, were selected for final analysis. In both groups, there was evidence of a lower testosterone concentration than in controls. Weighted mean differences were -0.38 nmol/l (95% confidence interval (CI) -0.55 to -0.22) and -0.29 nmol/l (95% CI -0.39 to -0.18), respectively. The mean differences represented a range of 1–49% lower (average 25%) in POI and a range of 11% higher to 77% lower (average 22% lower) for iatrogenic menopause. A sensitivity analysis of the three highest-quality studies in each group did not change the data substantially. The significance of such relatively small differences and their clinical importance are unclear.


  • Henry Burger
    Emeritus Director, Prince Henrys Institute of Medical Research, Clayton, Victoria, Australia


  1. Janse F, Tanahatoe SJ, Eijkemans MJC, Fauser BCJM. Testosterone concentrations, using different assays, in different types of ovarian insufficiency: a systematic review and meta-analysis. Hum Reprod Update 2012, April 23. Epub ahead of print.
  2. Burger HG, Dudley EC, Cui J, Dennerstein L, Hopper JL. A prospective longitudinal study of serum testosterone dehydroepiandrosterone sulphate and sex hormone binding globulin levels through the menopause transition. J Clin Endocrinol Metab 2000;85:2832-8.
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