Adipose tissue is an endocrine organ and has a role in the metabolism of sex steroids. Central obesity in women appears to impair reproduction even in the absence of PCOS. Potential mechanisms of subfertility in obese women include IR with hyperinsulinemia, which stimulates ovarian androgen production, as well as increased peripheral aromatization of androgens. Altogether, these events may modify gonadotropin secretion pattern altering follicular development [15]. In subfertile couples, it has been shown that the probability of spontaneous pregnancy declined linearly with the women’s body mass index (BMI) [16]. These data suggest that obesity per se may impair reproduction in women.

It is well known that sexual maturation depends on total body fat and tends to occur earlier in overweight and obese girls. Women who experienced early menarche have higher BMI in adult life compared to the late-maturing girls; data from animal and human studies suggest that leptin may be the link between total body fat and the onset of menarche [17]. This association between earlier menarche and adult obesity may be considered as the beginning of the interaction between body weight, metabolism, and reproduction which persists throughout the female reproductive life; earlier age of menarche, in fact, increases the risk of adult T2DM, and this appears to be mediated by greater adult adiposity [18].

PCOS is the most frequent ovarian disorder in premenopausal women (6–10 %), and obesity is a common feature of this endocrinopathy (present in 20–69 % of patients) [19]. PCOS is a heterogeneous disorder characterized by multiple endocrine disturbances, and its underlying causes are likely to be both genetic and environmental. It is possible that this condition begins prenatally, and the consequences extend past in the reproductive years, with multigenerational impact [20]. The fundamental pathophysiologic defect in PCOS is not known, but changes in insulin action, gonadotropin dynamics, as well as ovarian and steroidogenic defects have all been shown to contribute to the disorder.

According to the ESHRE (European Society of Human Reproduction and Embryology)/ASRM (American Society for Reproductive Medicine) consensus and to the evidence-based clinical practice guidelines of an Endocrine Society-appointed task force [21], PCOS can be diagnosed in a woman presenting with two out of three of the following features:

During the physical examination, it is important to assess the cutaneous manifestations (hirsutism, acne, alopecia, acanthosis nigricans, and skin tags), using grading systems that minimize the subjectivity of the evaluations, and to record BMI and waist circumference, as visceral obesity worsens the severity of the PCOS phenotype and increases the incidence of PCOS-related metabolic risk factors. A 2-h oral glucose tolerance test using a 75-g oral glucose load is also recommended to screen for impaired glucose tolerance (IGT) andT2M, and rescreening within 5 years is suggested. Different phenotypes such as “ovulatory PCOS” and “nonhyperandrogenic PCOS” have received much criticism and probably represent less severe forms. Women with PCOS face a lifetime of reproductive and metabolic risk, but the focus of attention has been on fertility, which remains a challenge for many women with this condition. Reduced fertility, however, seems to be present only in the presence of oligo-ovulation or anovulation, but there is no clear data of the fertility of patients with PCOS who have normal ovulatory function. IR is recognized to be the key pathophysiological element of PCOS and a significant contributor to its reproductive and metabolic complications [23, 24]. PCOS patients often display other indices of cardiovascular risk such as dyslipidemia, high serum homocysteine, and inflammatory markers (serum TNF and IL-6) [1]. They also present clinical features of premature atherosclerosis such as impaired pulse wave velocity, increased carotid intima-media wall thickness, presence of carotid plaque, and increased coronary artery calcification [25, 26]. Despite the prevalence and health implications of PCOS, clinical gaps exist including delayed diagnosis, inconsistent management, inadequate support for lifestyle change, and limited attention to psychological and metabolic features. Intervention was needed to improve awareness, patient experience, early diagnosis, self-management, complication screening, and treatment across reproductive, metabolic, and psychological features [27].

Increased serum insulin stimulates ovarian androgen production and also reduces sex hormone-binding globulin (SHBG) production in the liver further increasing serum levels of free bioavailable androgens. Apart from reproductive (anovulation) and cosmetic (acne, alopecia, and hirsutism) consequences of elevated serum androgens in women, hyperandrogenemia can increase abdominal obesity, which in turn further aggravates existing IR. Preadipocytes are known to have androgen receptors, and high androgen levels have been shown to induce selective IR in cultured adipocytes. Conversely, adipokines secreted by the intra-abdominal adipose tissue may also promote ovarian androgen production. TNF may directly stimulate proliferation and steroidogenesis in the rat theca cells and is involved in the apoptosis and anovulation in the rat’s ovary. Additionally, intra-abdominal fat tissue has been shown to express several enzymes involved in the metabolism of androgens which may further contribute to the hyperandrogenism in women with PCOS [28].

Recently, there has been interest in whether EDCs in the environment, particularly bisphenol A (BPA), may contribute to the disorder. A growing body of research documents the effects of EDCs on the differentiation of adipocytes and the central nervous system circuits that control food intake and energy expenditure [29]. In parallel, interest has grown in epigenetic influences, including maternal programming, the process by which the mother’s experience has permanent effects on energy-balancing traits in the offspring [30]. In animal models, exposure to BPA during the perinatal period dramatically disrupts ovarian and reproductive function in females. BPA also appears to have obesogenic properties, disrupting normal metabolic activity and making the body prone to overweight. In humans, cross-sectional data suggest that BPA concentrations are higher in women with PCOS than in reproductively healthy women, but the link of causality has not been established, and additional work is needed to understand the mechanisms by which EDCs may contribute to PCOS as well as the critical periods of exposure, which may even be transgenerational [31].

The use of diagnostic criteria established during the consensus conference held in Rotterdam in 2003 is recommended in adults, whereas in adolescent and perimenopausal and postmenopausal women, the diagnostic criteria for PCOS have not been validated [32]. Of particular concern is that many of the features considered to be diagnostic for PCOS may evolve over time and change during the first few years after menarche. Nonetheless, attempts to define young women who may be at risk for development of PCOS are pertinent since associated morbidity such as obesity, IR, and dyslipidemia may benefit from early intervention. Some suggest that even using the strictest criteria, the diagnosis of PCOS may not be valid in adolescents younger than 18 years. In addition, evidence does not necessarily support that lack of treatment of PCOS in younger adolescents will result in untoward outcomes since features consistent with PCOS often resolve with time [33].

Age-dependent cessation of ovarian functions is associated with a disruption of metabolic homeostasis and consequent inflammatory reactions that trigger the onset of metabolic, cardiovascular, skeletal, and neurologic pathologies. Recent data show that obese menopausal patients are not protected from osteoporosis [34, 35]. With menopause, estradiol levels decrease markedly, although estrone levels remain at reproductive level. In adipose tissue, estrogens increase subcutaneous fat deposition in lower body areas and decrease lipolytic activity, and when estrogen signaling decreases, the subcutaneous fat redistributes to visceral areas and increases hepatic fat deposition [36, 37]. These phenomena can be reversed by the administration of hormone replacement therapy (HRT) that might aid the restoration of metabolic homeostasis and highlight the pathogenic mechanisms underlying the disordered energy metabolism associated with human ovarian dysfunction. Furthermore, PCOS is common among reproductive-aged women (8–10 %). Although the medical and metabolic consequences of PCOS are well described in young women, its impact on female reproductive senescence and the menopausal transition is poorly understood [38]. Randomized controlled clinical trials should be carried out to better evaluate the long-term effects of oral contraceptives or HRT in women. The use of contraceptives can deteriorate glucose tolerance; however, low estrogen doses when administered orally can improve tolerance. Recent evidences suggest that genistein aglycone and phytoestrogens may act beneficially on surrogate cardiovascular risk markers in postmenopausal women and on bone loss [39–41].

Lifestyle modification studies to reduce IR in obese women with PCOS are limited by small numbers, lack of controls, and variable methodologies used to evaluate IR. Small reductions in weight (∼5 % body weight) have led to positive clinical improvements, but long-term dietary restriction is generally difficult to maintain, while specific dietary recommendations lack evidences. Beneficial effects of exercise in women with PCOS have been proved: a 3-month structured exercise training program caused significant improvement in cardiopulmonary functional capacity, IR, and BMI and after 6 months even restored ovulation [42]. Young patients show very good compliance to lifestyle modifications (unlike adult women), and loss of body weight can result in a spontaneous resumption of menstrual cycles. There are very few data on different kinds of diets (Mediterranean, hyperproteic) and on the role of physical exercise alone in not obese PCOS patients.

Considering the reciprocal interactions between pathways that control fertility and energy metabolism and the key roles of molecules such as estrogens and IGF-1 in these pathways, these new data could challenge current therapeutic strategies—amelioration of metabolic disorders, for example, might become an important goal of hormone replacement therapy (HRT) in menopausal obese women. Women with PCOS, however, frequently present a number of risk factors that could be absolute or relative contraindications to the use of a contraceptive pill. Insulin sensitizers have been used to control body weight gain in patients with PCOS, and most of the data demonstrate that metformin surely improves insulin sensitivity and show evidences of benefit on parameters of MetS (reduction of blood pressure and low-density lipoprotein cholesterol) [43]. The effects of other insulin sensitizers such as glitazones have also been evaluated in patients with PCOS [44]. Treatment with orlistat, a potent inhibitor of gastric and pancreatic lipase which impairs digestion of dietary fats, combined with hypocaloric diet apart from decreasing body weight also led to a reduction of serum insulin and androgen levels in obese PCOS patients [45]. The new guidelines [31] do not recommend the use of inositols, thiazolidinediones, or statins, considering that the latter may improve chronic inflammation and lipid profile but impair insulin sensitivity in women with PCOS [46], and suggest the use of metformin only in women with glucose intolerance. Metformin is well known to improve the ovarian response to clomiphene citrate, improve the likelihood of mono-ovulatory cycles and lower the risk of ovarian hyperstimulation syndrome [47]. Common sense also suggests using metformin in young patients with PCOS who do not require immediate infertility treatment [48].

Bariatric surgery should only be advocated to morbidly obese individuals after careful evaluation of the risk-to-benefit ratio. According to the current National Institute of Health clinical recommendations, surgical treatment of obesity should be considered when BMI is greater than 40 or greater than 35 in patients with a high-risk obesity-related condition following failure of other treatments for weight control [49, 50]. Results from uncontrolled studies assessing the effect of bariatric surgery in morbidly obese women with PCOS reported sustained weight loss and complete resolution of all features defining PCOS, including hirsutism, hyperandrogenism, menstrual irregularity, anovulation, and improved menstrual cyclicity as well as natural conception [51].

The main risk factors for breast cancer are associated with reproductive status, genetic, lifestyle, ethnicity, and anthropometric characteristics [52, 53]. In particular, overweight and obesity have been clearly associated with an increased overall risk of breast cancer. These associations appeared to be extremely consistent for postmenopausal breast cancer, but there is still controversy on their impact on the risk of premenopausal breast cancer. An inverse association between BMI and the risk of premenopausal breast cancer, with a 50 % reduction in risk among obese women and an 8 % reduction in risk per 5 kg m⁻² increase in BMI, has been reported. A recent meta-analysis shows that obesity (BMI) is predictive of an adverse clinical outcome in both premenopausal and postmenopausal breast cancer and that (Waist to Hip Ratio) WHR and height are associated with a small increase of this risk. Overall, this analysis suggests that WHR as a marker of the intra-abdominal (central) fat has a positive impact on the risk of breast cancer [54].