Prevalence of 'obesity-associated gonadal dysfunction' in severely obese men and women and its resolution after bariatric surgery: a systematic review and meta-analysis

Abstract

Background: Sexual dimorphism manifests noticeably in obesity-associated gonadal dysfunction. In women, obesity is associated with androgen excess disorders, mostly the polycystic ovary syndrome (PCOS), whereas androgen deficiency is frequently present in obese men in what has been termed as male obesity-associated secondary hypogonadism (MOSH). Obesity-associated gonadal dysfunction, consisting of PCOS in women and MOSH in men, is a frequent finding in patients with severe obesity and it may be ameliorated or even resolve with marked weight loss, especially after bariatric surgery.

Objective and rationale: We aimed to obtain an estimation of the prevalence of obesity-associated gonadal dysfunction among women and men presenting with severe obesity and to evaluate the response to bariatric surgery in terms of resolution and/or improvement of this condition and changes in circulating sex hormone concentrations.

Search methods: We searched PubMed and EMBASE for articles published up to June 2016. After deleting duplicates, the abstract of 757 articles were analyzed. We subsequently excluded 712 articles leaving 45 studies for full-text assessment of eligibility. Of these, 16 articles were excluded. Hence, 29 studies were included in the quantitative synthesis and in the different meta-analyses. Quality of the studies was assessed using the Quality index for prevalence studies and the Quality Assessment Tool for Before-After (Pre-Post) Studies With No Control Group available from the National Heart, Lung and Blood Institute. For meta-analyses including more than 10 studies, we used funnel and Doi plots to estimate publication bias.

Outcomes: In severely obese patients submitted to bariatric surgery, obesity-associated gonadal dysfunction was very prevalent: PCOS was present in 36% (95CI 22-50) of women and MOSH was present in 64% (95CI 50-77) of men. After bariatric surgery, resolution of PCOS was found in 96% (95CI 89-100) of affected women and resolution of MOSH occurred in 87% (95CI 76-95) of affected men. Sex hormone-binding globulin concentrations increased after bariatric surgery in women (22 pmol/l, 95CI 2-47) and in men (22 pmol/l, 95CI 19-26) and serum estradiol concentrations decreased in women (-104 pmol/l, 95CI -171 to -39) and to a lesser extent in men (-22 pmol/l, 95CI -38 to -7). On the contrary, sex-specific changes were observed in serum androgen concentrations: for example, total testosterone concentration increased in men (8.1 nmol/l, 95CI 6-11) but decreased in women (-0.7 nmol/l, 95CI -0.9 to -0.5). The latter was accompanied by resolution of hirsutism in 53% (95CI 29-76), and of menstrual dysfunction in 96% (95CI 88-100), of women showing these symptoms before surgery.

Wider implications: Obesity-associated gonadal dysfunction is among the most prevalent comorbidities in patients with severe obesity and should be ruled out routinely during their initial diagnostic workup. Considering the excellent response regarding both PCOS and MOSH, bariatric surgery should be offered to severely obese patients presenting with obesity-associated gonadal dysfunction.

Keywords: androgens; estradiol; estrogens; gonadotropins; hirsutism; male obesity-associated secondary hypogonadism; menstrual dysfunction; polycystic ovary syndrome; sex hormone-binding globulin; testosterone.