The effects of androgen therapy in women with premature ovarian insufficiency: A systematic review

Background: Premature ovarian insufficiency (POI) is a disorder of increasing occurrence and has multiple long-term impacts on affected females’ health; one of which is sexual dysfunction. Testosterone has been shown to improve hypoactive sexual desire disorder in postmenopausal women. Traditional hormone replacement therapy (estrogen and progesterone) is known for its beneficial effects in these cases, but there is still no scientific evidence to support the use of androgen in this situation. Objective: Critically review and assess the literature on the use of androgen preparations in women with premature ovarian insufficiency (POI). Search Strategy: Database search included randomized controlled trials, prospective comparative, observational, non-randomized studies, and case series of 10 or more subjects with no time limit restrictions. Selection criteria: Eligible trials included females below the age of 40, with amenorrhea >4 months, FSH >40 IU/L on two occasions separated by six weeks. Results: 539 abstracts were double screened, identifying 6 eligible studies; 3 randomized prospective double blinded studies, one randomized placebo controlled, one prospective observational, and one retrospective study. Discrepancies were arbitrated by a third reviewer. Androgen preparations included DHEA, danazol, and testosterone patch. Trials studied the impact of androgen on menstrual pattern, ovarian reserve markers, fertility outcomes, mood, self-esteem, and bone mineral density (BMD). Conclusion: There was no significant effect of androgen supplementation on mood, self-esteem, or bone mineral density. Although one study demonstrated an increase in ovarian volume and antral follicular count, there was no significant change in ovarian reserve, ovarian function, fertility outcome or menstrual pattern. Clinical Trial Registration: Trial was registered with open science framework (OSF), DOI: 10.17605/OSF. IO/2MYUV