Obesity-Related Hypogonadism in Women

Abstract

Obesity-related hypogonadotropic hypogonadism is a well-characterized condition in men (termed male obesity-related secondary hypogonadism; MOSH); however, an equivalent condition has not been as clearly described in women. The prevalence of polycystic ovary syndrome (PCOS) is known to increase with obesity, but PCOS is more typically characterized by increased gonadotropin-releasing hormone (GnRH) (and by proxy luteinizing hormone; LH) pulsatility, rather than by the reduced gonadotropin levels observed in MOSH. Notably, LH levels and LH pulse amplitude are reduced with obesity, both in women with and without PCOS, suggesting that an obesity-related secondary hypogonadism may also exist in women akin to MOSH in men. Herein, we examine the evidence for the existence of a putative non-PCOS "female obesity-related secondary hypogonadism" (FOSH). We précis possible underlying mechanisms for the occurrence of hypogonadism in this context and consider how such mechanisms differ from MOSH in men, and from PCOS in women without obesity. In this review, we consider relevant etiological factors that are altered in obesity and that could impact on GnRH pulsatility to ascertain whether they could contribute to obesity-related secondary hypogonadism including: anti-Müllerian hormone, androgen, insulin, fatty acid, adiponectin, and leptin. More precise phenotyping of hypogonadism in women with obesity could provide further validation for non-PCOS FOSH and preface the ability to define/investigate such a condition.

Graphical Abstract

Figure 1.

Mechanisms of hypogonadism in male obesity-related secondary hypogonadism (MOSH). Abbreviations: GnRH, gonadotropin releasing hormone; LH, luteinizing hormone; FSH, follicle stimulating hormone; SHBG, sex hormone binding globulin; NEFA, Non-esterified fatty acids; IL, interleukin; TNF-α, tumor necrosis factor.

Figure 2.

Mechanisms of polycystic ovary syndrome (PCOS) in lean women. Abbreviations: GnRH, gonadotropin releasing hormone; LH, luteinizing hormone; FSH, follicle-stimulating hormone; SHBG, sex hormone–binding globulin; E2, estradiol; AMH, anti-Müllerian hormone; PCOS, polycystic ovary syndrome.

Figure 3.

Putative mechanisms of female obesity-related secondary hypogonadism in women with obesity. Abbreviations: GnRH, gonadotrophin releasing hormone; LH, luteinizing hormone; FSH, follicle-stimulating hormone; SHBG, sex hormone–binding globulin; E2, estradiol; AMH, anti-Müllerian hormone; PCOS, polycystic ovarian syndrome; NEFA, nonesterified fatty acids; IL, interleukin; TNF-α, tumor necrosis factor.