Department of Endocrinology and Metabolism, Hospital Universitario Ramón y Cajal & Universidad de Alcalá, E-28034 Madrid, Spain.
Diabetes, Obesity and Human Reproduction Group, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) & Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.
Hum Reprod Update. 2017 Jul 1;23(4):390-408. doi: 10.1093/humupd/dmx012.
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.
背景:性二态性在肥胖相关的性腺功能障碍中表现得非常明显。在女性中,肥胖与雄激素过多症有关,主要是多囊卵巢综合征(PCOS),而雄激素缺乏在肥胖男性中很常见,这种情况被称为男性肥胖相关的继发性性腺功能减退症(MOSH)。肥胖相关的性腺功能障碍,包括女性的 PCOS 和男性的 MOSH,在严重肥胖患者中很常见,体重明显减轻,特别是在接受减肥手术后,这种情况可能会得到改善或甚至得到解决。
目的和理由:我们旨在评估严重肥胖患者中与肥胖相关的性腺功能障碍的患病率,并评估减肥手术对该疾病的反应,包括该疾病的缓解和/或改善以及循环性激素浓度的变化。
搜索方法:我们在 PubMed 和 EMBASE 上搜索截至 2016 年 6 月发表的文章。删除重复项后,分析了 757 篇文章的摘要。随后排除了 712 篇文章,留下 45 篇文章进行全文评估资格。其中,16 篇文章被排除。因此,29 项研究被纳入定量综合分析和不同的荟萃分析。使用国家心肺血液研究所提供的患病率研究质量指数和无对照组的前后(Pre-Post)研究质量评估工具评估研究的质量。对于包括 10 项以上研究的荟萃分析,我们使用漏斗图和 Doi 图来估计发表偏倚。
结果:在接受减肥手术的严重肥胖患者中,与肥胖相关的性腺功能障碍非常普遍:PCOS 见于 36%(95%CI 22-50)的女性,MOSH 见于 64%(95%CI 50-77)的男性。减肥手术后,96%(95%CI 89-100)的受影响女性的 PCOS 得到缓解,87%(95%CI 76-95)的受影响男性的 MOSH 得到缓解。减肥手术后,女性的性激素结合球蛋白浓度增加了 22 pmol/L(95%CI 2-47),男性增加了 22 pmol/L(95%CI 19-26),女性的雌二醇浓度降低了 104 pmol/L(95%CI -171 至 -39),而男性的雌二醇浓度降低了 22 pmol/L(95%CI -38 至 -7)。相反,血清雄激素浓度观察到性别特异性变化:例如,男性的总睾酮浓度增加了 8.1 nmol/L(95%CI 6-11),但女性的总睾酮浓度降低了 0.7 nmol/L(95%CI -0.9 至 -0.5)。后者伴随着 53%(95%CI 29-76)的多毛症缓解和 96%(95%CI 88-100)的月经功能障碍缓解,这些症状在手术前出现在女性中。
更广泛的影响:肥胖相关的性腺功能障碍是严重肥胖患者最常见的合并症之一,在初始诊断评估中应常规排除。考虑到 PCOS 和 MOSH 都有很好的反应,减肥手术应该提供给患有肥胖相关性腺功能障碍的严重肥胖患者。
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