Carol L. Kuhle

Long-term health consequences of premature or early menopause and considerations for management

Abstract Aim To review the current evidence concerning the long-term harmful effects of premature or early menopause, and to discuss some of the clinical implications. Material and methods Narrative review of the literature. Results Women undergoing premature or early menopause, either following bilateral salpingo-oophorectomy or because of primary ovarian insufficiency, experience the early loss of estrogen and other ovarian hormones. The long-term consequences of premature or early menopause include adverse effects on cognition, mood, cardiovascular, bone, and sexual health, as well as an increased risk of early mortality. The use of hormone therapy has been shown to lessen some, although not all of these risks. Therefore, multiple medical societies recommend providing hormone therapy at least until the natural age of menopause. It is important to individualize hormone therapy for women with early estrogen deficiency, and higher dosages may be needed to approximate physiological concentrations found in premenopausal women. It is also important to address the psychological impact of early menopause and to review the options for fertility and the potential need for contraception, if the ovaries are intact. Conclusions Women who undergo premature or early menopause should receive individualized hormone therapy and counseling.

Prescribing menopausal hormone therapy: an evidence-based approach

The constantly changing landscape regarding menopausal hormone therapy (MHT) has been challenging for providers caring for menopausal women. After a decade of fear and uncertainty regarding MHT, reanalysis of the Women’s Health Initiative data and the results of recent studies have provided some clarity regarding the balance of risks and benefits of systemic MHT. Age and years since menopause are now known to be important variables affecting the benefit-risk profile. For symptomatic menopausal women who are under 60 years of age or within 10 years of menopause, the benefits of MHT generally outweigh the risks. Systemic MHT initiated early in menopause appears to slow the progression of atherosclerotic disease, thereby reducing the risk of cardiovascular disease and mortality. During this window of opportunity, MHT might also provide protection against cognitive decline. In older women and women more than 10 years past menopause, the risk-benefit balance of MHT is less favorable, particularly with regard to cardiovascular risk and cognitive impairment. For women entering menopause prematurely (<40 years), MHT ameliorates the risk of cardiovascular disease, osteoporosis, and cognitive decline. Nonoral administration of estrogen offers advantages due to the lack of first-pass hepatic metabolism, which in turn avoids the increased hepatic synthesis of clotting proteins, C-reactive protein, triglycerides, and sex hormone-binding globulin. The duration of combined MHT use is ideally limited to less than 5 years because of the known increase in breast cancer risk after 3–5 years of use. Limitations to use of estrogen only MHT are less clear, since breast cancer risk does not appear to increase with use of estrogen alone. For women under the age of 60 years, or within 10 years of onset of natural menopause, MHT for the treatment of bothersome menopausal symptoms poses low risk and is an acceptable option, particularly when nonhormonal management approaches fail.

''Go4Life'' exercise counseling, accelerometer feedback, and activity levels in older people §

Older people are more sedentary than other age groups. We sought to determine if providing an accelerometer with feedback about activity and counseling older subjects using Go4Life educational material would increase activity levels. Participants were recruited from independent living areas within assisted living facilities and the general public in the Rochester, MN area. 49 persons aged 65-95 (79.5±7.0 years) who were ambulatory but sedentary and overweight participated in this randomized controlled crossover trial for one year. After a baseline period of 2 weeks, group 1 received an accelerometer and counseling using Go4Life educational material (www.Go4Life.nia.nih.gov) for 24 weeks and accelerometer alone for the next 24 weeks. Group 2 had no intervention for the first 24 weeks and then received an accelerometer and Go4Life based counseling for 24 weeks. There were no significant baseline differences between the two groups. The intervention was not associated with a significant change in activity, body weight, % body fat, or blood parameters (p>0.05). Older (80-93) subjects were less active than younger (65-79) subjects (p=0.003). Over the course of the 48 week study, an increase in activity level was associated with a decline in % body fat (p=0.008). Increasing activity levels benefits older patients. However, providing an accelerometer and a Go4Life based exercise counseling program did not result in a 15% improvement in activity levels in this elderly population. Alternate approaches to exercise counseling may be needed in elderly people of this age range.

Effect of exercise on anthropometric measures and serum lipids in older individuals: a systematic review and meta-analysis

Objectives Overweight and obesity are increasing in individuals over age 60 years. This systematic review quantifies the effect of exercise on body mass index (BMI), waist circumference (WC) and lipids in overweight and obese individuals over the age of 60 years. Settings Nine randomised controlled trials conducted in Brazil, Great Britain, Iceland, Japan and the USA compared aerobic and/or resistance exercise with a control group. Participants Final analysis reviewed 1166 participants over the age of 60 years for 3–9 months. Primary outcome measures This study reviewed the effects of exercise on BMI, WC and low-density lipoprotein (LDL). Results Exercise produced a significant reduction in BMI (−1.01 kg/m2, 95% CI −2.00 to −0.01) and WC (−3.09 cm, 95% CI −4.14 to −2.04) but not LDL cholesterol (−0.31 mg/dL, 95% CI −0.81 to 0.19). Analyses revealed substantial heterogeneity likely due to the type and intensity of exercise. Data on adverse effects were minimal. The overall level of evidence is moderate due to imprecision and heterogeneity. Conclusions Exercise in overweight and obese older individuals improves anthropometric measures such as BMI and WC. The effect of exercise on serum lipids is unclear.

Menopausal hormone therapy in cancer survivors: A narrative review of the literature

Decision making regarding the use of menopausal hormone therapy (MHT) for the treatment of bothersome menopausal symptoms in a cancer survivor can be complex, and includes assessment of its impact on disease-free or overall survival. Estrogen receptors are present in several cancer types, but this does not always result in estrogen-mediated tumor proliferation and adverse cancer-related outcomes. Estrogen may even be protective against certain cancers. Menopausal hormone therapy is associated with an increased risk of recurrence and mortality after diagnosis of some cancer types, but not others. We provide a narrative review of the medical literature regarding the risk of cancer recurrence and associated mortality with initiation of MHT after the diagnosis of breast, gynecologic, lung, colorectal, hematologic cancers, and melanoma. Menopausal hormone therapy may be considered for management of bothersome menopausal symptoms in women with some cancer types (e.g., colorectal and hematologic cancer, localized melanoma, and most cervical, vulvar and vaginal cancers), while nonhormonal treatment options may be preferred for others (e.g., breast cancer). In women with other cancer types, recommendations are less straightforward, and the use of MHT must be individualized.

A negative view of menopause: does the type of symptom matter?

Abstract Objectives: To assess the association between the type of symptom and women’s self-reported view of menopause. Methods: The study was conducted at Mayo Clinic, Rochester MN, between January 2006 and October 2014. Women aged 40–64 were included. Data from 1420 women were analyzed in a cross-sectional design. The Menopause Health Questionnaire was used for symptom assessment. Odds ratios (ORs) and population attributable risk (PAR) (OR × percent frequency) were calculated for each symptom. Logistic regression analyses were performed with the view of menopause as the dependent variable. Results: Anxiety (2.34), depressed mood (2.24), irritability (2.22), vaginal itching (2.27), crying spells (2.1) and breast tenderness (2.08) were associated with highest odds of having a negative view of menopause. Highest PAR (population impact) symptoms were anxiety (22.27), weight gain (20.66), fatigue (20.28) and irritability (19.41). Hot flushes and night sweats, although common, were not associated with a negative view of menopause (OR 1.3 and 1.16; PAR 3.85 and 4.42, respectively). Conclusion: Mood symptoms, vaginal itching, weight gain, breast tenderness and fatigue, although less common than hot flushes, were noted to have greater association with a negative view of menopause. Specifically addressing these symptoms during menopausal consultation may improve patient satisfaction and outcomes.

Recommendations for hormone therapy in hysterectomized women: importance of new data in clinical management

Women with a prior hysterectomy with and without oophorectomy represent special cohorts among those who require menopausal hormone therapy (HT), as a progestogen is not required for endometrial protection. This is relevant in light of recent research demonstrating superiority of estrogen therapy alone compared with estrogen plus a progestogen with respect to breast cancer risk and perhaps even cardiovascular protection. No longer is it appropriate to lump all HT regimens together when advising patients. Unfortunately, there is a general reluctance in the healthcare community to prescribe HT even a decade after publication of the results of the Women’s Health Initiative trial. However, with subsequent research showing a favorable benefit/risk balance of short-term estrogen therapy in symptomatic, recently menopausal women, especially those who have undergone hysterectomy with oophorectomy, the need for educating patients and providers on the matter cannot be overemphasized.

Data Registry on Experiences of Aging, Menopause, and Sexuality (DREAMS): A cohort profile

The Womens Health Clinic (WHC) at Mayo Clinic in Rochester, Minnesota, has provided consultative care to women with menopausal and sexual health concerns since 2005. Clinical information on the 8688 women seen in the WHC through May 2017 who gave consent for the use of their medical records in research is contained in the Data Registry on Experiences of Aging, Menopause, and Sexuality (DREAMS). Initially, DREAMS was created to improve the clinical care of women, but it has become a valuable research tool. About 25% of the DREAMS women have been seen in the WHC 2 or more times, allowing for passive longitudinal follow-up. Additionally, about 25% of the DREAMS women live in the 27-county region included in the expanded Rochester Epidemiology Project medical records linkage system, providing additional information on those women. The cohort has been used to investigate associations between: caffeine intake and vasomotor symptom bother; recent abuse (physical, sexual, verbal, and emotional) and menopausal symptoms; specific menopausal symptoms and self-reported view of menopause; and obstructive sleep apnea risk and vasomotor symptom severity and the experience of vasomotor symptoms in women older than 60 years. A study nearing completion describes a clinical series of over 3500 women presenting for sexual health consultation by sexual function domain and by decade of life. Other studies under way are determining correlates with sexual health and dysfunction. Planned studies will investigate associations between the experience with menopause and the risk of disease.