The impact of obesity on women’s health

WHY IS OBESITY IMPORTANT IN WOMEN’S HEALTH? The presence of obesity has a profound impact on many aspects of women’s health. The accumulation of excess adipose tissue causes physiological changes that affect multiple organs and systems.1,2 These changes are linked to many conditions, including type 2 diabetes (T2D), cardiovascular disease (CVD), obesity-related cancers, osteoarthritis, kidney disease, venous thromboembolism (VTE), metabolic dysfunction-associated steatotic liver disease (MASLD), gynecological disorders, and mental health conditions (Table 1).1,2 This article will explore the impact of obesity on female physiology at different stages of life and discuss how obesity is related to different health conditions.TABLE 1: Summary of the health risks associated with obesityTHE IMPACT OF OBESITY AT DIFFERENT STAGES IN A WOMAN’S LIFE Obesity has a multisystemic impact on female physiology at various stages of life through its effects on lipotoxicity, oxidative stress, and activation of the inflammatory response.2-4 As the primary healthcare professional (HCP) for many women with obesity, it is important for obstetrics and gynecology (OB-GYN) HCPs to bear in mind that CVD is the leading cause of death for women in the United States,5 and is responsible for ≈ 1 in 3 deaths (compared with ≈ 1 in 32 for breast cancer).6 Obesity is a major contributor to cardiovascular (CV) risk, both through its impact on CV risk factors such as hypertension, T2D, dyslipidemia, and sleep disorders, and through its contribution to CVD and CV mortality independently of its association with other risk factors.5,7 Reproductive years: preconception During the reproductive years, obesity can impact multiple aspects of a woman’s health. Women with obesity have an increased likelihood of experiencing early puberty, dysfunctional uterine bleeding, dysregulated menstrual cycles, and ovulatory disorders relative to those with a healthy body mass index (BMI).8-10 Polycystic ovary syndrome (PCOS), which affects ≈ 1 in 10 women of childbearing age, is typically diagnosed in women aged 20-40 years.11 Obesity contributes to PCOS development in those who are genetically predisposed and, conversely, PCOS can also contribute to worsening of obesity.11,12 Evidence points to significant associations between BMI and features of PCOS at all ages,13 and a substantial proportion of women with PCOS have overweight or obesity (reported prevalence 38%-88%).14 Obesity is strongly associated with fertility issues in women with PCOS through its impact on inflammation, hyperinsulinemia, and insulin resistance.12 The mechanisms linking PCOS and obesity that play a role in fertility issues are shown in Fig. 1.FIG. 1: Summary of the mechanisms linking obesity and PCOS that contribute to fertility issues. IR, insulin resistance; LH, luteinizing hormone; PCOS, polycystic ovary syndrome; SHBG, sex hormone binding globulin. Figure reproduced from Hazlehurst JM, et al Clin Endocrinol (Oxf). 2022;97(2):208-216 with permission as per Creative Commons license CC BY-NC 4.0 https://creativecommons.org/licenses/by-nc/4.0/.12In women both with and without PCOS, the consequences of obesity in terms of fertility are well known. Studies have shown that obesity is associated with reduced fecundity and increased time to conception, irrespective of menstrual regularity, parity, age, or smoking.15,16 Given these associations, women with obesity make up a high proportion of those seeking medical assistance to become pregnant. In one study of 5823 US women aged 20-44 years, rates of infertility testing were higher in women with class 1 (BMI 30 to<35 kg/m2) or class 2-3 (BMI ≥ 35 kg/m2) obesity than those with overweight (BMI 25 to<30 kg/m2) or a healthy BMI (18.5 to<25 kg/m2), at 30.4% and 32.6% versus 17.8% and 27.0%, respectively.17 Moreover, those with obesity also have an elevated risk for poor outcomes with assisted reproductive technology. A systematic review and meta-analysis showed that women with obesity are significantly less likely to have a live birth following in vitro fertilization (IVF) than those with a healthy BMI, with a risk ratio (RR) of 0.85.18 Studies looking at individual components of the IVF process have demonstrated that obesity is associated with unpredictable or poor ovarian response following hormonal stimulation,4,19,20 a smaller number of aspirated and mature oocytes,21 abnormal oocyte morphology,22 impaired embryo development,23,24 lower pregnancy rate after embryo transfer,25 and an elevated risk of pregnancy loss.26 Reproductive years: pregnancy Obesity is also associated with elevated risks following successful conception.4,27 Women with obesity are more likely than those with a healthy BMI to have pregnancy complications, including miscarriage, preeclampsia, gestational diabetes, and hypertension,28,29 in addition to an elevated risk of antepartum complications and Cesarean section delivery.28 In terms of infant measures, obesity is linked to higher rates of adverse outcomes, including stillbirth, preterm birth, sudden unexpected infant death, macrosomia, and congenital anomalies.28-30 The links between obesity and pregnancy-associated risks are summarized in Fig. 2.FIG. 2: Pregnancy-related risks associated with obesity. LGA, large for gestational age.27-30For women who do not wish to become pregnant, there are important considerations regarding contraception use in those with obesity. Several types of steroid-based contraceptives, including combined oral contraceptives (COCs), progestin-only pills (POPs), transdermal patches, and the vaginal ring, have shown reduced effectiveness in women with obesity.9 For instance, a study of 1005 women who were using intravaginal levonorgestrel contraception estimated that rates of pregnancy (ie, contraception failure) were 9.8% per year for a woman weighing 80 kg, compared with just 1.7% for a woman weighing 40 kg.31 A systematic review of 11 trials found that BMI ≥ 25 kg/m2 was associated with increased pregnancy risk while taking oral COCs, with an odds ratio of 1.91 relative to those with BMI<25 kg/m2.32 Similarly, data from a cohort study of over 50,000 US women identified higher rates of oral contraception failure among those with BMI ≥ 35 kg/m2 versus<35 kg/m2 after adjustment for age, education level, and parity (hazard ratio=1.5).33 Obesity may also have an impact on the risk profiles associated with different contraceptive options. In women taking COCs, the risk of VTE was shown to be more than twice as high in those with obesity relative to a healthy BMI, indicating that other VTE risk factors should be taken into account to determine individual risk.2,34 The US Centers for Disease Control and Prevention has categorized different contraception options according to their risks and benefits in women with obesity (Table 2). While the majority of contraceptives are assigned to Medical Eligibility Criteria for Contraceptive Use (MEC) category 1 and have no restriction on use, combined hormonal contraceptives (CHCs) are designated MEC category 2 in women with a BMI ≥ 30 kg/m2, meaning that the advantages generally outweigh the theoretical or proven risks.35 The CDC warns that CHCs may increase VTE risk to an unacceptable level if multiple other risk factors are present in addition to obesity, such as diabetes, smoking, and dyslipidemia.35 Furthermore, POPs and COCs are assigned MEC category 3, indicating that the theoretical or proven risks outweigh the advantages in women with a history of malabsorptive bariatric surgery (ie, procedures that shorten the functional length of the small intestine to decrease absorption of calories and nutrients).35 Contraception choice in women with obesity requires an individualized approach that considers other health conditions, risk factors, and medications.2TABLE 2: CDC MEC categories for contraception use in women with obesity or prior bariatric surgeryMidlife and perimenopause Beyond the reproductive years, obesity frequently affects women in midlife and during the menopausal transition as they experience physiological and lifestyle changes. Findings from the US Study of Women’s Health Across the Nation suggested that women gain ≈ 1.5 lb (0.7 kg) per year in the midlife period (age range 42-52 years at study baseline), irrespective of previous body size or race/ethnicity, which increases their risk of moving from a healthy BMI to overweight or obesity.36 Coupled with the associations between obesity and multiple chronic conditions, these observations led to the development of a national guideline aimed at preventing unhealthy weight gain and preventing disease in middle-aged women.37 Specifically, the guideline recommends that women aged 40-60 years with BMI in the healthy or overweight range (18.5-29.9 kg/m2) should be advised to “maintain weight or limit weight gain to prevent obesity and its associated health conditions.”37 There are multiple, bidirectional relationships between obesity and menopause. While a direct association between menopause and decreased metabolic rate has not been demonstrated, there is a considerable decrease in metabolic rate with increasing age.38 Furthermore, the menopausal transition is associated with increased obesity, loss of lean muscle mass, shift from a gynecoid to an android body fat distribution pattern, increased abdominal fat accumulation, especially visceral adipose tissue, and an altered postprandial glycemic response.39-42 All of these factors are associated with increased CV and metabolic risks.40 Data from a study of the Women’s Health Initiative, conducted at 40 centers in the United States, showed that postmenopausal women with abdominal obesity (waist circumference>88 cm) had a higher risk of mortality and CV mortality than those without abdominal obesity, even among those with a BMI in the healthy range.43 While menopause is associated with increased risk of obesity and associated cardiometabolic morbidity, studies have also shown that obesity could lead to worsening menopause-related symptoms and conditions. For instance, obesity and excess body fat during perimenopause are associated with increased incidence and severity of vasomotor symptoms (VMS).40,44,45 It has been suggested that these associations could be explained by the excess subcutaneous adipose tissue that is present in women with obesity, which provides insulation and prevents heat dissipation.40 Obesity has also been linked to sleep problems during menopause, with one study showing that postmenopausal women with obesity have significantly higher scores in two polysomnography measures -- respiratory disturbance index and apnea-hypopnea index -- relative to those with a healthy BMI.46 Conversely, sleep problems may represent a risk factor for obesity in the perimenopausal period; evidence suggests that sleep loss is associated with endocrine and metabolic changes, including increased ghrelin and decreased leptin production, reduced glucose tolerance, and altered nutrient utilization.47,48 These changes can lead to altered appetite regulation and increased hunger, particularly for calorie-rich foods.47 Common sleep problems occurring in the perimenopausal period include obstructive sleep apnea, insomnia, and restless legs syndrome.46,49 Data also support an association between obesity and urinary incontinence (UI) in postmenopausal women.50 It has been shown that women with obesity are at increased risk for UI,51 and a meta-analysis demonstrated strong associations between obesity, abdominal pressure, and bladder pressure in middle aged and older women.52 Furthermore, sexual dysfunction is an important issue that can occur around the time of menopause, and evidence suggests additional links with obesity.50 In a study of 221 postmenopausal women, those with obesity had significantly higher dysfunction scores for desire and arousal, and significantly lower sexual satisfaction scores, than those with a healthy BMI.53 The causes of sexual dysfunction in postmenopausal women with obesity are complex and multifactorial, and may include: adipokine dysregulation; comorbidities such as sleep apnea, T2D, and UI; insulin resistance; hormonal alterations; poor body image and low self-esteem; stigma; and mental health conditions such as anxiety and depression.54 In summary, there are numerous associations between obesity and different physiological changes and conditions affecting midlife and perimenopausal women. It is important for women’s HCPs to be aware of these associations and to ensure early detection and treatment of issues such as sleep problems and sexual dysfunction to optimize health outcomes and quality of life. Moreover, OB-GYNs must bear in mind that obesity is a key contributor to CVD risk, which remains the leading cause of death in women in the United States. HCPs, therefore, have a crucial role in recognizing and managing obesity to reduce CVD risk and improve overall health outcomes. OBESITY AND PSYCHOLOGICAL HEALTH Further to its profound impact on physical health, obesity is associated with increased psychosocial burden, with a disproportionate effect on women. In one study published in 2024, BMI and waist-height ratio significantly correlated with increased depression scores and decreased well-being scores in 1821 individuals aged 46-73 years, after adjustment for demographic and lifestyle factors.55 When results were stratified by biological sex, the relationship between BMI and depression was stronger in women than in men (β coefficient=0.8 [P=0.007] vs. 0.6 [P=0.049]).55 Moreover, evidence suggests that women with obesity may have an elevated risk for suicidal ideation. One study showed that increased BMI was associated with both major depression and suicidal ideation among women, but in men the reverse was true, with higher odds of both outcomes in those with lower BMI.56 Obesity also contributes to anxiety disorders, with research indicating that the presence of obesity is associated with a ≈ 25% increased risk of anxiety disorder in the US general population.57 In women specifically, overweight and obesity are associated with increased lifetime risk of any anxiety disorder, generalized anxiety disorder, social phobia, and specific phobia.58 Challenges with body image and disordered eating frequently affect women with obesity. A systematic review and meta-analysis of 17 studies found that people with obesity are significantly more likely to report body image dissatisfaction than those with a healthy BMI, with stronger associations in women than men.59 Many individuals with obesity report problems with disordered eating, including eating for emotional reasons, binge eating disorder, and difficulty controlling portion sizes and eating frequency.60 In a study of 690 US women with eating disorders (EDs), those with obesity had more severe ED correlates and related clinical impairment, in addition to higher levels of depression and anxiety, than those with a healthy BMI.61 Data on mental healthcare service use support the associations between obesity and poor psychological health. Approximately half of candidates for bariatric surgery report prior mental health treatment, and ≈ 40% report treatment at the time of surgery.60 One study of 24,766 individuals undergoing bariatric surgery showed that the proportion of individuals attending mental healthcare services increased after surgery, with a 58% increase in emergency department attendance and a 29% increase in hospitalization for mental health.62 These findings highlight the need to be aware of the risk for poor psychological health in women with obesity, including in the period following bariatric surgery. SUMMARY AND CONCLUSIONS Taken together, evidence shows that obesity has substantial consequences for various aspects of physical and mental health over the course of a woman’s lifetime. It is, therefore, essential that women’s HCPs are aware of the impact of obesity and understand their role in proactively addressing obesity with women under their care.