Hormonal Contraception and Sexual Function: A Review, Clinical Insights, and Management Considerations.

Most sexually active women of reproductive age have used contraception, with hormonal methods constituting approximately 40% of contraceptive choices. Among these hormonal options, combined oral contraceptives stand out as the most selected. Within this same demographic, sexual issues are prevalent. Although specific hormonal contraceptives have been implicated in sexual dysfunction among these women, the correlation lacks consistency across studies and varies between different types of hormonal contraception. This article assesses the available literature on the associations between various hormonal contraceptive methods and sexual function and provides practical management insights.

Menopause in the workplace: Challenges, impact, and next steps.

INTRODUCTION: Menopause is a natural part of a woman's life that coincides with a time when many women play significant roles in the workforce. Menopause symptoms, such as hot flashes, fatigue, and difficulty with concentration and memory, can have a negative effect on work productivity and efficiency. OBJECTIVES: This paper summarizes the impact of menopause in the workplace, with an emphasis on the impact of symptoms on employed women and how the workplace influences their experiences. It highlights economic implications, promotes awareness, and suggests potential next steps. METHODS: A search for papers was conducted between August and November 2023 in the PubMed and Medline databases. Papers were selected based on personal experience and interpretation of the findings. Recommendations for managing menopause symptoms in the workplace and guidance on an optimal workplace intervention strategy were provided. RESULTS: Women experiencing severe menopause symptoms are more likely to report adverse work outcomes, including absenteeism and job-related decisions such as quitting, retiring early, or declining promotions than women experiencing few symptoms. Factors such as a lack of awareness about menopause, inflexible work conditions, and high-stress jobs can exacerbate the severity of these symptoms. Additionally, unaddressed menopause symptoms contribute to both direct and indirect economic costs, including medical resource utilization and lost work productivity, resulting in a substantial economic burden. CONCLUSION: Menopause symptoms impair women's work experiences and productivity. In addition to dismantling the stigma associated with menopause, it is critical to create and implement menopause workplace policies and interventions aimed at supporting women in this universal life stage.

Risks and benefits of hormone therapy after menopause for cognitive decline and dementia: A conceptual review.

OBJECTIVE: The effects on the brain of hormone therapy after the onset of menopause remain uncertain. The effects may be beneficial, neutral, or harmful. We provide a conceptual review of the evidence. METHODS: We 1) provide a brief history of the evidence, 2) discuss some of the interpretations of the evidence, 3) discuss the importance of age at menopause, type of menopause, and presence of vasomotor symptoms, and 4) provide some clinical recommendations. RESULTS: The evidence and the beliefs about hormone therapy and dementia have changed over the last 30 years or more. Five recent observation studies suggested that hormone therapy is associated with an increased risk of dementia, and the association appears not to change with the timing of initiation of therapy. These harmful associations may be explained by a causal effect of hormone therapy on the brain or by several confounding mechanisms. We suggest that the use of hormone therapy should be customized for different subgroups of women. It may be important to subgroup women based on age at onset of menopause, type of menopause, and presence or absence of vasomotor symptoms. In addition, the effects may vary by type, dose, route, and duration of administration of estrogens and by the concurrent use of progestogens. DISCUSSION: The relation of hormone therapy with the risk of dementia is complex. Hormone therapy may have beneficial, neutral, or harmful effects on the brain. Hormone therapy should be guided by the clinical characteristics of the women being treated.

Weight loss response to semaglutide in postmenopausal women with and without hormone therapy use.

OBJECTIVE: To compare weight loss response and changes in cardiometabolic risk markers in postmenopausal women using semaglutide with and without menopause hormone therapy (HT) use. METHODS: Retrospective cohort study of postmenopausal women treated with semaglutide for overweight or obesity for ≥3 months. Endpoints: total body weight loss percentage (TBWL%) at 3, 6, 9, and 12 months after semaglutide initiation; and percentage of women achieving ≥5% and ≥10% TBWL and changes in cardiometabolic risk markers (glucose, blood pressure, and lipids) at 12 months. RESULTS: There were 16 women on HT and 90 on no-HT; mean age 56 ± 8 vs 59 ± 8 yr, P = 0.2 and mean BMI 36 ± 5 vs 39 ± 8 kg/m 2 , P = 0.1; respectively. Among women on no-HT, White race, dyslipidemia, and depression were more prevalent. Women on HT had a higher TBWL% at 3, 6, 9, and 12 months: 7 ± 3% vs 5 ± 4%, P = 0.01; 13 ± 6% vs 9 ± 5%, P = 0.01; 15 ± 6% vs 10 ± 6%, P = 0.02; and 16 ± 6% vs 12 ± 8%, P = 0.04; respectively. After adjusting for potential confounders, this association remained significant across time. At 12 months, a greater percentage of women on HT achieved ≥5% and ≥10% TBWL. Both groups experienced an improvement in cardiometabolic risk markers. CONCLUSION: In postmenopausal women with overweight or obesity treated with semaglutide, HT use was associated with an improved weight loss response. This association was maintained when adjusted for confounders. Larger studies should be conducted to confirm these results.

Menopause transition and cardiovascular disease risk.

The risk of cardiovascular disease (CVD) notably increases in the fifth decade of a woman's life, coinciding with the onset of menopause and occurring 10 years later than the similar age-related increase in men. Menopause marks a significant transition in a woman's life and is accompanied by cardiometabolic changes, including a shift in body composition, increased blood pressure, disruptions in lipoproteins, and insulin resistance. There is increasing evidence that the menopause transition is a risk factor for CVD, independent of age-related changes, especially considering that the earlier the onset of menopause, the greater is the CVD risk. Further, menopause-related symptoms such as vasomotor symptoms, sleep disturbances, and mood changes may all have a direct impact on CVD risk. In this review, we summarize the current literature regarding CVD in midlife women, focusing on the cardiometabolic changes related to ovarian aging versus chronological aging, as well as those related to specific menopause characteristics, including age, type of menopause and the use of menopause hormone therapy.

Association of resilience with female sexual dysfunction.

OBJECTIVES: Female sexual dysfunction (FSD), a common concern affecting women of all ages, is often mediated by important psychological factors. Resilience has been shown to correlate with psychological well-being across different groups of people. The aim of this study was to assess if there is an association between resilience and FSD. STUDY DESIGN: This cross-sectional study included 4,366 women (mean [SD] age, 51.7 [11]) seen in women's health clinics at 1 of 3 geographic Mayo Clinic locations. Participants completed the Brief Resilience Scale, the Female Sexual Function Index (FSFI), and the Female Sexual Distress Scale-Revised (FSDS-R). MAIN OUTCOME MEASURES: We used univariate and multivariable logistic regression analyses to assess associations between resilience, sexual function, and sexual distress, adjusting for potential confounding variables. RESULTS: FSD criteria (FSFI ≤26.55 and FSDS-R ≥ 11) were met by 55.8 % of women. Low, normal, and high levels of resilience were reported by 17.3 %, 57.1 %, and 25.6 % of participants, respectively. The univariate analysis showed that higher resilience was associated with lower sexual distress, lower odds of FSD, and better sexual function. Multivariable analysis adjusted for potential confounders showed that the association persisted and that higher resilience correlated with better sexual function and lower odds of FSD. CONCLUSIONS: In this large cross-sectional study, women with higher resilience scores had better sexual function and lower odds of FSD. Additional studies with diverse women are needed to confirm this association and to determine whether women with FSD could benefit from enhancing resilience as a therapeutic strategy.

Weight Gain in Midlife Women.

PURPOSE OF REVIEW: To summarize the evidence and clinical implications of weight and body composition changes during midlife in women and provide an overview of weight gain prevention and management in this population. RECENT FINDINGS: Aging-related changes such as decreased energy expenditure and physical activity are important culprits for weight gain in midlife women. The hormonal changes of menopause also influence body adiposity distribution and increase central adiposity. These body changes can have health consequences including the development of cardiometabolic diseases, osteoarthritis, cancer, worsening in cognition, mental health, and menopause symptoms. Midlife women experience changes related to aging, menopause, and lifestyle which favor weight gain. Clinical practice should focus on early counseling and anticipatory guidance on the importance of dietary changes and physical activity to attenuate this phenomenon. Future research should focus on the longitudinal relationship between weight trends in midlife and health consequences and mortality.

Association between obesity and female sexual dysfunction: a review.

INTRODUCTION: Obesity is a global health crisis that has been growing over the past few decades. The economic burden associated with obesity is substantial as it is associated with multiple disabling chronic diseases, such as cardiovascular disease, certain cancers, osteoarthritis, chronic pain, and mental illness. Obesity is known to be a risk factor for sexual dysfunction in men, but this association is less well understood in women. AIMS: To provide a narrative review of the available literature on the relationship between overweight/obesity and female sexual dysfunction, elaborate on the possible mechanisms explaining this association, and discuss the effects of weight loss on sexual function in those with obesity. METHODS: A search of the medical literature was carried out in PubMed and Medline, focusing on original research and systematic reviews of original research on obesity and sexual function in women. RESULTS: The relationship between obesity and female sexual function is not consistent across studies. While women with obesity are more likely to have worse sexual function and avoid sexual activity, many studies have failed to identify these associations. Lifestyle changes resulting in weight loss lead to better sexual function, and bariatric surgery has been shown to improve sexual function in the first couple of years following the procedure; yet, the long-term effects of weight loss and bariatric surgery are still uncertain. CONCLUSIONS: The evidence on the relationship between obesity and female sexual function is mixed. Nevertheless, weight loss has been shown to improve sexual function in women with obesity. The impact of weight loss medications and the long-term effect of bariatric surgery on female sexual function require further study.

History of infertility and sexual dysfunction in midlife women: Is there a link?

BACKGROUND: Infertility has been linked with an increased risk of sexual dysfunction in reproductive-aged women, with longer periods of infertility associated with a greater risk. AIM: The study's aim was to examine whether a history of infertility treatment in women is linked to sexual dysfunction during midlife. METHODS: The cross-sectional study was conducted among sexually active women, between the ages of 45 and 65 years, who sought consultation at the women's health clinics at a US tertiary care center. History of infertility treatment was assessed with a single question that asked participants if they were treated for infertility in the past. The association between a history of infertility treatment and sexual dysfunction-which was diagnosed by a combination of Female Sexual Function Index score ≤26.55 and Female Sexual Distress Scale-Revised score ≥11-was assessed in a multivariable logistic regression model that adjusted for multiple confounders. OUTCOMES: The primary outcome was sexual dysfunction in midlife women. RESULTS: The analysis included 5912 women, with a mean age of 54.1 years. Nearly 16% of women reported receiving treatment for infertility. More than half the women (55%) had sexual dysfunction: 56.3% of those with previous fertility treatments and 54.4% of those without any fertility treatment (P = .3). Receiving treatment for infertility in the younger years did not significantly increase the odds of sexual dysfunction in midlife in univariate (odds ratio, 1.08; 95% CI, 0.94-1.24; P = .3) and multivariable analyses (odds ratio, 1.11; 95% CI, 0.96-1.29; P = .17). CLINICAL IMPLICATIONS: While infertility is known to be predictive of sexual dysfunction in women during their reproductive years, there was no association between a history of infertility treatment and sexual dysfunction in midlife women in the current study. STRENGTHS AND LIMITATIONS: The study used validated questionnaires accounting for sexual complaints and distress and adjusted for multiple confounding factors. Limitations include the selection bias introduced by the study of women presenting for evaluation of sexual dysfunction, which may have been a result of factors stronger than the influence of infertility. Other limitations include the study's cross-sectional nature with suboptimal racial and ethnic representation. CONCLUSION: Although infertility is commonly associated with female sexual dysfunction in women of reproductive age, the association was not present in midlife women in the current study.

The effect of genetic variation in estrogen transportation and metabolism on the severity of menopause symptoms: A study from the RIGHT 10K cohort.

OBJECTIVE: The severity of menopause-related symptoms varies considerably among women. The determinants of this variation are incompletely understood. The aim of this study was to assess the association between genetic variation in estrogen metabolism and transport pathways and the severity of menopause symptoms. METHODS: This was a cross-sectional study of 60 peri- and postmenopausal women in the Mayo Clinic RIGHT study (which involved sequencing of genes involved in drug metabolism and transport), who had also been evaluated in the Women's Health Clinic at Mayo Clinic in Rochester, MN. All participants completed the Menopause Rating Scale (MRS) for assessment of menopause symptoms, including hot flashes. The association between severity of menopause symptoms and the variation in genes encoding 8 enzymes and transporters involved in estrogen metabolism was evaluated. RESULTS: Lower CYP3A4 activity and higher COMT activity were associated with lower severity of somatic menopause symptoms (p = 0.04 and 0.06, respectively). These associations did not persist after adjustment for hormone therapy use. No differences in MRS scores or hot flash severity were noted among other genetic variant groups. Age at natural menopause was not affected by variations in the genes studied. CONCLUSION: The current study did not show an association between genetic variation in estrogen metabolism and transport pathways and the severity of menopause symptoms. Further studies with larger sample sizes may be required to understand this potentially complex association.

Associations between childhood adversity and age at natural menopause.

OBJECTIVE: Adverse childhood experiences (ACEs) are reported in more than half of the women in the United States and have been shown to negatively impact the menopause experience. The objective of this study was to evaluate the association between ACEs and age at natural menopause. METHODS: This is a cross-sectional study conducted among participants of the Data Registry on the Experiences of Aging, Menopause, and Sexuality (DREAMS). The registry included women who were seen for consultations in the women's health clinic at Mayo Clinic, Rochester, between May 2015 and December 2016. Only postmenopausal women were included in this analysis. Childhood adversity was assessed with the validated ACE questionnaire. Age at natural menopause was self-reported. The association between ACEs and age at menopause was evaluated using a multivariable linear regression model adjusting for multiple confounders. RESULTS: A total of 350 women were evaluated. The mean age was 59.2 years, and a majority were White (92.9%), married/partnered (82%), and educated (91.2% with at least some college education). Women with a history of at least four ACEs were estimated to reach natural menopause 1.3 years sooner than women with no ACE in multivariable analysis, but the results were not statistically significant (95% confidence interval, -3.2 to 0.6; P = 0.18). CONCLUSIONS: Although stressful life experiences such as ACEs may negatively influence health for midlife women, this study did not find an association with the age at natural menopause.

The association between menopausal hormone therapy and gastroesophageal reflux disease: a systematic review and meta-analysis.

IMPORTANCE AND OBJECTIVE: Gastroesophageal reflux disease (GERD) is a chronic condition associated with several risk factors, but little is known about the association between hormone therapy (HT) and GERD in postmenopausal women. EVIDENCE REVIEW: We investigated the association between ever or current menopausal HT use and GERD using a systematic review and meta-analysis. Studies published between 2008 and August 31, 2022, were pooled using a DerSimonian and Laird random-effects model, and outcomes were reported as adjusted odds ratios (aOR) with a corresponding 95% CI. FINDINGS: The pooled analysis of five studies found a significant direct association between estrogen use and GERD (aOR, 1.41; 95% CI, 1.16-1.66; I2 = 97.6%), and progestogen use and GERD (two studies: aOR, 1.39; 95% CI, 1.15-1.64; I2 = 0.0%). The use of combined HT was also associated with GERD (1.16; 95% CI, 1.00-1.33; I2 = 87.9%). Overall, HT use was associated with 29% higher odds for GERD (aOR, 1.29; 95% CI, 1.17-1.42; I2 = 94.8%). The large number of pooled participants, differences in study design, geography, patient characteristics, and outcome assessment resulted in significant high heterogeneity. CONCLUSIONS AND RELEVANCE: There is a significant association between ever or current HT use and GERD. However, the results should be interpreted with caution, given the small number of included studies and high heterogeneity. This warrants careful evaluation of GERD risk factors when prescribing HT to reduce the risk of potential GERD complications.

Association of Migraine and Vasomotor Symptoms.

OBJECTIVE: To further examine a potential link between migraine and vasomotor symptoms as well as hypertension as a cardiovascular disease risk factor, potentially explaining the association in midlife women. PATIENTS AND METHODS: We conducted a cross-sectional analysis from the Data Registry on Experiences of Aging, Menopause, and Sexuality using questionnaire data from women aged 45 to 60 years seen in women's clinics at a tertiary care center from May 15, 2015, through January 31, 2022. A history of migraine was self-reported; menopause symptoms were assessed with the Menopause Rating Scale. Associations between migraine and vasomotor symptoms were evaluated utilizing multivariable logistic regression models adjusting for multiple factors. RESULTS: Of 5708 women included in the analysis, 1354 (23.7%) reported a migraine history. The total cohort had a mean age of 52.8 years, most (5184 [90.8%]) were White, and 3348 (58.7%) were postmenopausal. In adjusted analysis, women with migraine were significantly more likely to have severe/very severe hot flashes vs no hot flashes compared with women without migraine (odds ratio, 1.34; 95% CI, 1.08 to 1.66; P=.007). Migraine was associated with a diagnosis of hypertension in adjusted analysis (odds ratio, 1.31; 95% CI, 1.11 to 1.55; P=.002). CONCLUSION: This large cross-sectional study confirms an association between migraine and vasomotor symptoms. Migraine also was associated with hypertension, potentially providing a link with cardiovascular disease risk. Given the high prevalence of migraine in women, this association may help identify those at risk for more severe menopause symptoms.

Impact of Menopause Symptoms on Women in the Workplace.

OBJECTIVE: To evaluate the impact of menopause symptoms on work outcomes and to assess the estimated economic impact. PATIENTS AND METHODS: Women aged 45 to 60 years receiving primary care at 1 of the 4 Mayo Clinic sites were invited to participate in a survey study (Hormones and ExpeRiences of Aging) from March 1 through June 30, 2021. A total of 32,469 surveys were sent, with 5219 responses (16.1% response rate). Of the 5219 respondents, 4440 (85.1%) reported current employment information and were included in the study. The primary outcome was self-reported adverse work outcomes related to menopause symptoms assessed by the Menopause Rating Scale (MRS). RESULTS: The mean age of the 4440 participants was 53.9±4.5 years, with the majority being White (4127 [93.0%]), married (3398 [76.5%]), and educated (2632 [59.3%] college graduate or higher); the mean total MRS score was 12.1, signifying moderate menopause symptom burden. Overall, 597 women (13.4%) reported at least one adverse work outcome due to menopause symptoms; 480 women (10.8%) reported missing work in the preceding 12 months (median, 3 days missed). The odds of reporting an adverse work outcome increased with increasing menopause symptom severity; women in the highest quartile of total MRS scores were 15.6 (95% CI, 10.7 to 22.7; P<.001) times more likely to have an adverse work outcome vs those in the first quartile. Based on workdays missed due to menopause symptoms, we estimate an annual loss of $1.8 billion in the United States. CONCLUSION: This large cross-sectional study identified a major negative impact of menopause symptoms on work outcomes and the need to improve medical treatment for these women and make the workplace environment more supportive. Additional studies are needed to confirm these findings in larger and more diverse groups of women.

Frequency and type of premature or early menopause in a geographically defined American population.

OBJECTIVE: There is limited information on the prevalence of premature and early menopause. Therefore, we studied the frequency and type of premature (age < 40 years) or early (age 40-44 years) menopause in a geographically-defined American population. METHODS: We studied a random sample of women aged 18 to 50 years who resided in Olmsted County, MN between 1988 and 2007. Women were followed through December 2021, and age at cessation of menses was assessed via review of the medical records included in a medical records-linkage system. Menopause was defined as cessation of menses due to spontaneous or induced ovarian insufficiency. RESULTS: 1015 women (71.3 %) underwent spontaneous menopause, 138 (9.7 %) underwent bilateral oophorectomy, 17 (1.2 %) had antecedent chemotherapy or radiation therapy, and 254 (17.8 %) underwent hysterectomy or endometrial ablation. The median age at cessation of menses was 51.0 years (IQR, 49.0-52.0) for spontaneous menopause, 46.0 years (IQR, 41.0-49.0) for menopause induced by oophorectomy, chemotherapy, or radiation therapy, and 38.0 years (IQR, 33.0-44.0) for hysterectomy. Considering both spontaneous and induced menopause, the frequency was 3.1 % (95 % CI, 2.2-4.2) for premature and 6.2 % (95 % CI, 5.0-7.8) for early menopause. Considering only spontaneous menopause, the frequency reduced to 0.4 % (95 % CI, 0.2-1.0) for premature and 5.2 % (95 % CI, 4.0-6.8) for early menopause. However, considering all types of cessations of menses, the frequency was 12.2 % (95 % CI, 10.6-14.0) for premature and 9.7 % (95 % CI, 8.3-11.3) for early cessation of menses. DISCUSSION: Approximately 3 % of women in the general population experienced either spontaneous or induced premature menopause. The most common cause of premature menopause was bilateral oophorectomy.

Vasomotor Symptoms During Menopause: A Practical Guide on Current Treatments and Future Perspectives.

Vasomotor symptoms affect as many as 80% of midlife women, but only about one in four women receive treatment due to many factors. Menopausal hormone therapy remains the most effective treatment for vasomotor symptoms, and current professional guidelines conclude that the benefits of treatment typically outweigh the risks for healthy, symptomatic women under age 60 years and those within 10 years from their final menstrual period. For women with medical comorbidities, an individualized approach to treatment is recommended. For women who cannot use or choose not to use menopausal hormone therapy, there are many evidence-based non-hormonal options available including pharmacologic therapies. This review aims to summarize treatment options for bothersome vasomotor symptoms to guide clinicians caring for midlife women.

Rethinking Menopausal Hormone Therapy: For Whom, What, When, and How Long?

Menopausal hormone therapy (HT) was widely used in the past, but with the publication of seminal primary and secondary prevention trials that reported an excess cardiovascular risk with combined estrogen-progestin, HT use declined significantly. However, over the past 20 years, much has been learned about the relationship between the timing of HT use with respect to age and time since menopause, HT route of administration, and cardiovascular disease risk. Four leading medical societies recommend HT for the treatment of menopausal women with bothersome menopausal symptoms. In this context, this review, led by the American College of Cardiology Cardiolovascular Disease in Women Committee, along with leading gynecologists, women's health internists, and endocrinologists, aims to provide guidance on HT use, including the selection of patients and HT formulation with a focus on caring for symptomatic women with cardiovascular disease risk.