Weight Regulation in Menopause (2024)

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Abstract

Keywords: women, obesity, menopause, weight gain, treatment of obesity, weight loss

Introduction

Obesity is one of the largest epidemics in the world and is the mostprevalent chronic disease that continues to grow at an exponential rate within theUnites States (U.S.). With age adjusted prevalence of obesity in U.S. adultssurpassing 40% in data obtained from the U.S. National Health and NutritionExamination Survey (NHANES) for the first time in 2018, the efforts of public healthinitiatives and health care professionals have thus far been unsuccessful inreversing the course of this epidemic [1].

As a leading cause of mortality and morbidity, obesity is associated withnumerous health conditions including cardiovascular disease, diabetes, and severalcancers [2]. This epidemic continues to strainthe American healthcare system, with costs in the United States at an estimated113.9 billion dollars in the year 2008 alone [3]. Although there is no significant difference in the prevalence ofobesity between women and men, severe obesity, which is highly correlated with poorhealth outcomes, is more prevalent in women [1]. fPathophysiologyfecause obesity is a major risk factor forcardiovascular disease, sleep apnea, metabolic syndrome, gallbladder disease,musculoskeletal disorders, several cancers, and all-cause mortality [4].

Over 43% of menopausal women have obesity, and the challenges that promotethese staggering rates, and barriers to effective treatment, are multifactorial[1]. During menopause, there is anincrease in fat mass and a decrease in lean muscle mass [5]. Additionally, medications used to combat the hormonaland physical changes of menopause in women, such as antidepressants and hormonetreatments, have been shown to promote considerable weight gain [4, 6, 7]. Currently, the treatment of obesity inmenopausal women mainly centers around lifestyle and diet changes. However, the longterm effectiveness of these approaches continues to be a challenge, and theintegration of pharmacotherapy and bariatric surgery is on the rise [8]. The objective of this review is to compile anddescribe relevant literature on the prevalence, pathophysiology, and clinicalmanagement of obesity in postmenopausal women.

Methods

In order to identify pertinent literature on the prevalence, pathophysiology,diagnosis, management, and prognosis of obesity in postmenopausal women, a searchwas conducted via PubMed of articles on life science and biomedical topics in theMEDLINE database. Articles published between the year 2000 and 2020 were selectedfor review to represent the most up to date evidence on the topic. Search terms usedin the PubMed search included women, obesity, menopause, aging, mid-age women,metabolism, weight gain, treatment of obesity, weight loss, bariatric surgery,weight loss medications, diet, physical activity, and behavior modification.Publications from the initial search were further refined to include thosedescribing studies that included postmenopausal women and addressed overweight andobesity. Publications describing the pathophysiology, clinical presentation,assessment, diagnosis, treatment, or prognosis of obesity in postmenopausal womenwere included. Publications that did not describe these factors related to obesityin postmenopausal women were excluded.

Pathophysiology

The menopausal state is associated with several hormonal changes. The mostnotable is the decreased levels of circulating estrogen that leads to severalphysiologic changes such as genital atrophy, loss of urogenital tissue support, andbone loss. These changes are promoted by a significant decrease in estradiol(E₂) and estrone (E₁). Estrone continues to be produced byperipheral aromatization while levels of estradiol, produced by the ovary, decline.The ovary, however, continues to produce androstenedione and testosterone. This, inconjunction with a decrease in levels of sex hormone binding globulin (SHBG), leadsto higher levels of free androgens [9].

A decrease in SHBG is implicated in the increase in prevalence of type 2diabetes and cardiovascular disease in postmenopausal women. Low SHBG and increasedcentral adiposity are risk factors for metabolic disease. In this population, thereis an accelerated increase in total cholesterol, which is explained by an increasein low-density lipoprotein cholesterol (LDL-C) [9]. During this time period the levels of high-density lipoprotein (HDL)cholesterol trend downwards also [9]. Thesechanges lead to deleterious cardiovascular effects in postmenopausal women [9].

The postmenopausal state is also associated with increases in total bodyweight. It has been documented that during the menopausal transition, women gain anaverage of 1 pound per year. However, average weight gain varies widely with 20% ofwomen gaining 10 pounds or more during this transition period [10]. This overall increase in body weight has not beenproven to have a direct correlation to changes in hormonal status, but it appears tobe related to increasing age and decreased energy expenditure [11, 12]. However,menopause is associated with increased abdominal subcutaneous and visceral adiposetissue deposition [13].

In pre-menopausal women, estrogens are responsible for the accumulation ofsubcutaneous adipose tissue deposition in the gluteal and femoral regions. Thisgynoid distribution has been linked to positive cardiometabolic effects such asdecreased insulin resistance. Androgens, in contrast, are responsible for theaccumulation of subcutaneous fat in the abdominal region, a metabolicallyunfavorable location. This central adiposity is associated with increasedcardiovascular and metabolic diseases, as well as decreased physical activity andpoorer quality of life [11]. Duringmenopause, an increase in follicle stimulating hormone (FSH) and decrease incirculating estradiol while androgen levels are maintained leads to relativehyperandrogenemia [14]. The decrease in theproduction of sex-hormone binding globulin during the menopausal transition alsoincrease the levels of bioavailable androgens [15]. This leads to a change in body composition that is characterized byan android fat distribution, with adipose tissue accumulating mostly in theabdominal area. There is also an increase in total visceral adipose tissue [16].

The relationship of estrogens and central adiposity in postmenopausal womenhas been shown to be bidirectional, suggesting that increased central adiposity mayalso lead to increased levels of estrogens. This occurs as a result of theproduction of estrogens from the peripheral conversion of androgens in adiposetissue (aromatization). Postmenopausal women with obesity have been shown to havehigher levels of estrogens when compared to nonobese women, though lower overallthan pre-menopausal women. However, these estrogens derived through peripheralaromatization have not been shown to be associated with positive cardiometaboliceffects such as reductions in insulin resistance and risk for diabetes andcardiovascular disease [14, 16]. This relationship also varies through the menopausaltransition, with highest future estradiol levels seen in later stages of menopausecompared to lower levels in early menopause [17].

In addition to these physiological hormonal changes, medications used tocombat the hormonal and physical changes of menopause in women, such asantidepressants like selective serotonin reuptake inhibitors (SSRIs) and serotoninand norepinephrine reuptake inhibitors (SNRIs), and hormone treatments, have beenshown to promote considerable weight gain [4,6, 7].

Clinical Presentation

The prevalence of overweight and obesity has increased significantly in theUnited States over the past decades, with greater than 70% of adults over the age of20 meeting criteria for overweight or obesity in 2016 compared to 56% in 1988 [18]. Rates are disproportionately higher inBlack (76%) and Hispanic (80%) communities compared to White (71%), and there ishigher prevalence in those making less than 400% of the federal poverty level (FPL)[18]. Rates of overweight and obesity arehigh with age for women 20 years and older, with 70% of women of perimenopausal agewith overweight or obesity. The incidence reaches a peak of 76% then declines afterthe age of 75 [18].

Because obesity is a major risk factor for cardiovascular disease, sleepapnea, metabolic syndrome, gallbladder disease, musculoskeletal disorders, severalcancers, and all-cause mortality [19]. TheUnited States Preventative Services Task Force (USPSTF) recommends screening foroverweight and obesity in all routine primary care physical examinations and torefer individuals with obesity for appropriate management [20]. The most frequently used screening method is BodyMass Index (BMI), the weight in kilograms divided by height in meters squared),which defines overweight as BMI ≥ 25- 29.9 kg/m² and obesity asBMI ≥ 30 kg/m² [21]. Thereis evidence that metabolic and cardiovascular disease risk depends on thedistribution of adipose tissue [22],therefore other assessments such as waist circumference, waist-to-hip ratio,skinfold thickness, bioelectric impedance, and more advanced imaging-basedtechniques may be better indicators of disease risk than BMI alone, particularly inpatients with increased muscle mass and those of non-European descent [23, 24].

Assessment and Diagnosis

Thfmedical and obstetric history, family history of obesity and associatedconditions, as well as a physical exam and laboratory evaluation obstetric history,family history of obesity and associated conditions, as well as a physical exam andlaboratory evaluation [25, 26]. As energy balance is vital to obesity management inpostmenopausal women, dietary inventory and physical activity assessment can yieldinsight into a patient’sfreening for eating disorders is paramount, asapproximately 30% of treatment-seeking individuals with obesity in the general adultpopulation are reported to have an eating disorder [25].

Screening for eating disorders is paramount, as approximately 30% oftreatment-seeking individuals with obesity in the general adult population arereported to have an eating disorder [26,27]. While binge eating disorder (BED)and bulimia are most common in this population, identification of any abnormaleating patterns, including binging, purging, lack of satiety, food-seeking behavior,and night-eating syndrome, is crucial [26].In postmenopausal women, disordered eating is also reported with 13% of women overage 50 years endorsing at least one eating disorder symptom. In addition, 60%reported the negative effect of personal weight concerns on their lives [28]. Weight promoting medications are also ofconcern. Several commonly used medications in postmenopausal women, includingbeta-blockers, psychotropic medications, and sleep medications, are associated withweight gain and metabolic dysfunction [29].Identification and modification of these medications will improve obesitymanagement.

The clinical presentation of a patient with obesity may include physicalfindings such as central adiposity, acanthosis nigricans, hirsutism, abdominalstriae, hepatomegaly, cardiomegaly, respiratory insufficiency, coxa vara and otherjoint deformities [26]. Clinicians shouldscreen patients for associated conditions with laboratory evaluation of glucose,Hemoglobin A1C, lipids, liver and thyroid function, as well as a sleep study,depression and cancer screenings and specialist referrals as clinically warranted[26]. The skilled clinician will alsoassess the patient’s readiness to treat their obesity and will work toreconcile any obstacles to treatment [30].

Treatment

A successful obesity treatment plan incorporates a culturally competentapproach to lifestyle and behavior modifications, as well as an assessment forpharmacologic and surgical candidacy. Nutrition is a key component of weightmanagement. Despite the extensive body of research on different dietary styles,there is a lack of sound evidence to recommend any one specific dietary plan overanother for the purposes of weight loss [31,32]. Emerging evidence on the effects ofintermittent fasting and time-restricted eating indicate metabolic benefits, howevereffects on weight loss are inconclusive [33,34]. Regardless of the particular dietaryapproach, any long-term weight loss and weight maintenance plan requires a reductionin energy intake from baseline [31]. This maybe achieved by reduced consumption of fat and processed food, smaller portion sizes,and increased energy density[31]. No matterthe approach taken, dietary changes must be safe, tolerable, affordable,nutritionally adequate, culturally acceptable and sustainable by the individual forweight loss and long-term weight maintenance [30, 35].

Physical activity with both aerobic and resistance training is alsonecessary for weight maintenance [31, 36, 37].Adults should do at least 150 to 300 minutes a week of moderate-intensity, or 75 to150 minutes a week of vigorous-intensity aerobic activity (or an equivalentcombination), as well as full-body muscle-strengthening activities on two or moredays a week [31, 38-40]. Higherdoses of exercises are recommended for patients with obesity due to the metabolicand cardiopulmonary benefits, and the attenuation of lean mass often lost withconcomitant caloric reduction [36, 39-43].

Patient preference, accessibility issues and physical limitations areimportant considerations when discussing an exercise regimen; options may includewater aerobics, dance, targeted resistance training, physical therapy,cardiopulmonary rehab and non-exercise activity thermogenesis (NEAT) [31, 44].

It should be acknowledged that weight loss is often less rapid and requiressustained effort in postmenopausal women. However, there are numerous healthbenefits from even 5-10% total body weight loss [45, 46]. The adoption ofhealthier dietary and physical activity approaches may lead to this moderate weightloss and the transition to metabolically healthy obesity, where evidence ofmetabolic dysfunction and the risk of adverse health outcomes is reduced. Thisalternative goal may be employed while continuing to pursue the long-term goal ofachieving normal weight in postmenopausal women with obesity [47, 48].

Pharmacotherapy has emerged as an impactful component of a comprehensiveapproach designed to achieve sustainable weight loss in patients with obesity. It isan effective intervention to support behavioral changes and dietary intervention,which alone may achieve limited weight loss that is difficult to maintain due toadaptive physiologic responses [49]. Weightloss pharmacotherapy has been recommended for the treatment of obesity in patientswith BMI ≥ 30 or in patients with overweight with a BMI ≥ 27 withassociated conditions such as type 2 diabetes, hypertension, and hyperlipidemia[45].

Currently, there are four medications approved for long term use by the Foodand Drug Administration (FDA) for the treatment of obesity: orlistat,phentermine/topiramate, naltrexone/bupropion, and liraglutide 3.0 mg [50]. The first medication approved for obesityin the United States was the sympathomimetic amine, phentermine, which is themedication most commonly prescribed for obesity in the United States for short termuse. Phentermine is also approved as a combination medication with topiramateextended release (phentermine/topiramate ER) for the chronic treatment of obesity.Other approved medications include orlistat, which decreases intestinal fatabsorption, and bupropion sustained release / naltrexone which combines adopamine/norepinephrine reuptake inhibitor and an opioid receptor antagonist.Liraglutide 3.0mg is a glucagon-like peptide-1 (GLP-1) receptor agonist that hasalso emerged as a promising pharmacologic treatment for obesity [51]. The potential effect of a reduction in insulinresistance seen with liraglutide may be particularly effective for the treatment ofobesity in post-menopausal women.

Despite the effectiveness of pharmacotherapy in the treatment of obesity,weight loss medications are prescribed by few clinicians. The rates of prescribingare even lower in older adults, including postmenopausal women. In this populationthere is an often a concern about the risk of adverse effects of weight lossmedications, however the continuing risk of progressive cardiometabolic diseaseshould so be considered in patients with poorly treated obesity [52].

Bariatric surgery is as an effective and sustainable treatment for obesityand obesity related conditions such as type 2 diabetes. Growing evidence fromlongitudinal and prospective studies have outlined the benefits of bariatric surgeryon mortality, weight loss, and obesity associated diseases in patients, fromadolescents to the older adults. Criteria for the surgical treatment of obesity wereestablished by a National Institutes of Health (NIH) consensus panel in 1991 whichoutlined the appropriateness of bariatric surgery for patients with BMI (≥40kg/m²) and for patients with BMI between 35-40 with certain obesityassociated conditions such as type 2 diabetes, heart disease, and obstructive sleepapnea. However, in recent years, data has supported the expansion of these criteria,including a suggested surgical indication type 2 diabetes for patients with BMI30-35 [53].

While a number of surgical options for the treatment of obesity have emergedover the last 50 years, adjustable gastric banding (AGB), the vertical sleevegastrectomy (VSG), and Roux-en-Y gastric bypass (RYGB), represent the majority ofsurgical procedures performed worldwide for the treatment of obesity [54]. These surgical treatment options have beenshown to not only be effective with weight loss of up to 50-60% of excess bodyweight, but they also have a rate of severe perioperative complications of less than1% [55]. In postmenopausal women, bariatricsurgery has been shown to be effective with 60-70% of excess body weight lossachieved at 12-24 months with RYGB. Though some evidence has shown that the weightloss effect of AGB is reduced in postmenopausal women when compared to women ofreproductive age, no differences in outcomes were seen after RYGB [56]. These findings support the use of bariatric surgeryto achieve weight loss in eligible postmenopausal women.

Prognosis

Obesity in postmenopausal women is associated with increased morbidity andmortality [57]. Prospective studies haveshown that a BMI ≥35 is associated with increased mortality in thispopulation [58]. These findings are to beexpected due to the association of obesity with a host of cardiometabolic diseasesincluding type 2 diabetes, cardiovascular disease, and hyperlipidemia. Theseconditions are all associated with increased morbidity and mortality with advancingage. Comprehensive care for patients with obesity may lead to improved outcomes.Increased physical activity, including aerobic exercises, in post-menopausal womenwho were previously sedentary, led to decreased adiposity for some patients a lowerrisk for breast cancer [59, 60]. In women with normal weight status, weight gain maybe mitigated in the peri- to postmenopausal period with increased physical activityand long-term dietary changes [61, 62].

Conclusion

In order to effectively impact the growing epidemic of obesity and itsprevalence among post-menopausal women, a comprehensive approach is needed. We mustacknowledge the obesity epidemic and the epidemiologic and physiologic factors thatpromote excess weight gain, understand the clinical assessment and diagnosticfactors, and utilize the full breadth of treatment options across the health carespectrum to optimize weight regulation in menopause in communities across theU.S.

Supplementary Material

Acknowledgments

Sources of funding: National Institutes of Health and Massachusetts GeneralHospital Executive Committee on Research (ECOR)(FCS), National Institutes of HealthNIDDK P30 DK040561 (FCS) and L30 DK118710 (FCS)

Footnotes

References