Liraglutide and polycystic ovary syndrome: is it only a matter of body weight?

Abstract

Despite Polycystic Ovary Syndrome (PCOS) is a very prevalent disorder among women of reproductive age, there is widespread agreement that until now, no pharmacological options are available to tackle the entire spectrum of clinical manifestations encountered in the clinical practice. Obesity and insulin resistance, which commonly characterized this syndrome, prompted the design of studies investigating the effects of glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RA) in PCOS. Indeed, a very impressive number of randomized controlled clinical trials (RCTs) and systematic reviews provided robust evidence on the effectiveness of GLP-1RA in PCOS as a new, appealing approach, producing both satisfactory and permanent weight loss, and improvement of insulin resistance at the same time. However, most of the subjects included in the RCTs are PCOS patients with obesity/overweight, whereas a portion of PCOS women, which can even reach 50%, might present a lean phenotype. Moreover, some benefits on clinical and metabolic features of PCOS may not have fully emerged due to the low or medium doses employed in the vast majority of the current studies. Thus, pitfalls in the methodology of these studies have led sometimes to misleading results. In addition, some aspects of GLP-1 beyond weight loss, such as preclinical evidence on GLP-1 effects in directly modulating the hypothalamus–pituitary–gonadal axis, or the effects of GLP-1RA on clinical and biochemical expression of hyperandrogenism, still deserve a greater insight, especially in light of a possible therapeutic use in PCOS women independently of obesity. Aim of this review is to further unravel the possible role of GLP-1 in PCOS pathogenesis, tempting to provide additional supports to the rationale of treatment with GLP-1RA in the management of PCOS also independent of weight loss. For this purpose, the outcomes of RCTs investigating in PCOS the anthropometric and metabolic changes have been treated separately to better underpin the effects of GLP-1 RA, in particular liraglutide, beyond weight loss.

Incretin Hormone Secretion in Women with Polycystic Ovary Syndrome: Roles of Obesity, Insulin Sensitivity and Treatment with Metformin and GLP-1s

“…Treatment with liraglutide also significantly reduced the area of visceral adipose tissue. Subcutaneously administered liraglutide at a dose of 3 mg once daily is indicated as an adjunct to chronic weight management in adults with a BMI of ≥30 kg/m 2 or a BMI of ≥27 kg/m 2 and at least one weight-related comorbidity, including hypertension, dyslipidemia, obstructive sleep apnea or type 2 diabetes [ 105 ].…”

“…Two studies investigated GLP-1 secretion in average-weight women with PCOS compared to age- and BMI-matched healthy women. In the first study, the authors examined fasting and post-meal GLP-1 levels and found that both levels were significantly reduced in the women with PCOS compared to the controls [ 105 ]. This finding suggests altered dynamics of incretin secretion in PCOS, which could contribute to the risk of type 2 diabetes.…”

“…There is growing interest in GLP-1RAs as potential treatments for obesity-related issues, including metabolic irregularities, hyperandrogenism, infertility and menstrual disruptions, particularly in women with polycystic ovary syndrome (PCOS) [ 106 ]. Nevertheless, it remains unclear whether the positive effects of GLP-1RAs in PCOS are solely attributable to weight loss and metabolic improvements, or if they also directly impact the hypothalamic–pituitary–gonadal (HPG) axis in PCOS [ 105 , 106 ].…”

“…Another regime included 10ηg of exenatide twice daily and 2 mg once weekly for 12 weeks [ 113 , 114 , 115 ]. Liraglutide was administered daily, as previously mentioned, with 1.2 mg up to 3.0 mg once daily [ 105 ]. Understanding the optimal dosing and treatment duration could significantly enhance the therapeutic use of GLP-1RAs in managing PCOS and its associated conditions.…”

Role of Mediterranean diet in endocrine diseases: a joint overview by the endocrinologist and the nutritionist

“…In fact, weight loss of at least 5% from baseline weight can improve or even normalize ovarian function [ 146 ]. Weight loss reduces insulin, sex hormone-binding globulin (SHBG), and estrogen levels; moreover, excess weight before conception is a major risk factor for fertility outcomes and it is well established that weight loss improves fertility in women with overweight and obesity [ 137 , 147 ].…”