Menopause is defined as the natural end to a woman’s menstrual cycle at the average age of 51 years and ranging between 45 and 55 years.¹ This period of time may also be associated with physiologic symptoms, such as vasomotor symptoms or “hot flashes,” mood lability, anxiety, depression, weight gain, insomnia, and fatigue. Many of these symptoms have been attributed to the menopausal transition secondary to a decline in ovarian function.¹ The percentage of obese individuals in our population can be assessed through the National Health and Nutrition Examination Survey (NHANES). The 2011–2012 survey data were assessed for body mass index (BMI) stratification²; they revealed that 33.9% of US adults aged 20 years and older were overweight, 35.1% were obese, and 6.4% were extremely obese, with a BMI greater than or equal to 40. These numbers jump significantly in the perimenopausal period. When assessed in the NHANES data set last so stratified in 2007 (showing no change in trends since 2003–2004), 41.1% of women aged 40–59 were obese compared to 30.5% aged 20–39 years. When evaluated by ethnicity, 53% of non-Hispanic black women, 51% of Mexican women, and 39% of non-Hispanic white women aged 40–59 were obese. Over age 60, these numbers increased to 61% for non-Hispanic black women but decreased to 37% for both non-Hispanic white and Mexican women.³ Baseline obesity can affect many of the symptoms described as well as potentially affect the perimenopausal-to-menopausal transition.¹

The physiology of menopause in all women surrounds the cessation of ovulation due to a loss of ovarian follicles, which in turn reduces ovarian production of estradiol, the most biologically active form of estrogen. This process then will cause an increase in circulating follicle-stimulating hormone (FSH) and a decrease in inhibin, which inhibits the release of FSH. The elevated FSH also increases the rate of follicular loss.⁴ Menopause is reached when the follicular number reaches approximately 1000.⁵

There has been some debate regarding the impact of obesity on the timing of menopause. There are studies that discussed an increase in BMI as positively associated with a later onset of menopause, using elevation of hormonal levels as a marker for timing.^6,7 There are also as many studies that showed no association between BMI and age of menopause onset. One study showed a modest prolongation of the age of menopause from 50.1 years to 50.4 years but using a BMI of 21.9 and 26.2, respectively.⁸ It is clear in these studies that current smoking was associated with an earlier age of menopause, and increasing parity delayed onset of menopause, but these are additional confounding factors in many of the studies in assessing obesity.^9,10 As the current existing data stand, obesity independent of smoking, parity, and exercise history cannot be associated with an early or late onset for timing of menopause. Newer studies looking at insulin resistance in conjunction with the metabolic syndrome rather than purely BMI cutoffs alone in comparison to age of final period or time of menopause seemed to show more of an association and may be the direction for further investigation.¹¹

Addressing perimenopausal and postmenopausal women with respect to their metabolic syndrome comorbidities rather than categorization purely by obesity class is clearly prudent given the fact that menopausal status alone is associated with a 60% increased risk of the metabolic syndrome even after adjusting for confounding factors, including age, BMI, household income, and activity. These factors include those listed in Table 31-1.

Postmenopausal women have an increase in total cholesterol, low-density lipoprotein (LDL), triglycerides, and lower high-density lipoprotein (HDL), with the greatest change in LDL during the perimenopausal-to-menopausal transition. Triglycerides also increase in the early postmenopausal period and are highly associated with increasing abdominal fat content and insulin resistance. Abdominal obesity is associated with hyperinsulinemia and type 2 diabetes risk.¹² During menopause, central obesity is greater as lipase activity is greater and response to lipolysis is lower. These changes result in decreasing estrogens, with the relative hyperandrogenism resulting in central obesity. Studies have shown such changes result in increased appetite, decreased exercise and lipolysis, as well as mood disorders, which are discussed further in this chapter.¹³ The menopausal transition will increase the risk for all women for central obesity, relative insulin insensitivity, and dyslipidemia.

A high waist circumference, reflective of central obesity and low sex hormone–binding globulin (SHBG) level are independent risk factors for metabolic disease in the perimenopausal transition.¹⁴ Cutoffs for morbidity of elevated risk for waist circumference is generally seen above 35 inches in women when compared with women with waist sizes of 28 inches or less. This risk translates to an increase in cardiovascular and cancer risk in these patients. Waist circumference has also been observed to increase in the perimenopause.¹⁵ The woman who enters menopause with preexisting central obesity and underlying baseline comorbidities will have a greater risk that will be further exacerbated with further weight gain.

In the obese as well as nonobese woman, the perimenopausal variation in hormonal function may cause irregular vaginal bleeding. In the obese perimenopausal patient, a decrease in progesterone in addition to an increase in androstendione conversion to estrone and decreased SHBG further exacerbate this pattern.¹⁶ While the average woman has a lifetime risk of endometrial cancer of 3%, the risk is doubled in overweight women (BMI > 25 to <29.5) and redoubled in obese women (BMI > 30). The same study that showed this increase also found a dose response to obesity exposure with increased risk of endometrial cancer in patients with persistence of obesity or magnitude of increase, with 35% weight gain in the 20s associated with a 10-year earlier diagnosis of endometrial cancer.¹⁷ This enhanced risk is in part secondary to the increase in circulating estrone and estradiol levels from adipose tissue,¹⁸ which is elevated by 40% in postmenopausal women with a BMI greater than 30.

The clinician must thus have a heightened awareness in this patient population and perform endometrial sampling as clinically indicated. Given the potential risk of anesthesia associated with patient habitus or comorbidities, including cardiovascular disease and sleep apnea, an office sample is preferred if technically possible. With an irregular bleeding pattern, an endometrial biopsy should be performed to rule out hyperplasia or cancer. For the perimenopausal patient with irregular bleeding and particularly in the obese patient, the first priority must be to rule out endometrial cancer. Some authors have suggested saline infusion sonography or transvaginal ultrasound on all such patients with irregular bleeding, but there are no endometrial thicknesses that consistently are predictive of hyperplasia or cancer in these patients. While intracavitary assessment is helpful in the diagnosis of other pathology, such as polyps or fibroids, sampling must be considered if the bleeding pattern is irregular in the perimenopausal patient, with risk further increased for the obese patient as outlined previously.¹⁹

When these patients are postmenopausal, sonographic assessment can be more useful. In a meta-analysis published by Timmermans et al. in 2010, studies evaluating various cutoffs for endometrial thickness in postmenopausal patients with vaginal bleeding were evaluated, revealing that it was a highly sensitive predictor for cancer of the uterus. At 4 mm, sensitivity was 94.8% with a specificity of 46.7%; at 5 mm, the sensitivity was 90.3% and the specificity was 54%; at 3 mm, sensitivity was increased to 97.9% but at a specificity of 35.4%.²⁰

A joint practice bulletin released by the American College of Obstetricians and Gynecologists and the Society of Gynecologic Oncology recommended premenopausal patients be evaluated clinically outside of their sonographic findings and sampled as clinically appropriate. This is because of the lack of correlation between thickness and hyperplasia or cancer in patients in the perimenopause or premenopausal period. With postmenopausal patients, it is appropriate to start evaluation directly with endometrial biopsy or sonography.²¹