Changes in Regional Fat Distribution and Anthropometric Measures Across the Menopause Transition

The Journal of Clinical Endocrinology & Metabolism · 2021 · 68 citations

• Medicine
• Endocrinology
• Demography

CONTEXT: The relation between the menopause transition (MT) and changes in regional fat distribution is uncertain. OBJECTIVE: To determine whether the MT is associated with the development of central adiposity. DESIGN: Longitudinal analysis from the Study of Women's Health Across the Nation, spanning 1996-2013 (median follow-up 11.8 years). SETTING: Community-based. PARTICIPANTS: 380 women with regional body composition measures by dual energy X-ray absorptiometry. Mean baseline age was 45.7 years; racial/ethnic composition was 16% Black, 41% Japanese and 43% White. OUTCOMES: Changes in android, gynoid and visceral fat and waist and hip circumferences. RESULTS: Android fat increased by 1.21% per year (py) and 5.54% py during premenopause and the MT, respectively (each P < 0.05). Visceral and gynoid fat began increasing at the MT, annualized changes were 6.24% and 2.03%, respectively (each P < 0.05). Postmenopausal annual trajectories decelerated to 1.47% (visceral), 0.90% (android), and -0.87% (gynoid), (all non-zero, P < 0.05). Waist girth grew during premenopause (0.55% py), the MT (0.96% py), and postmenopause (0.55% py) (all non-zero, P < 0.05; not statistically different from each other). Hip girth grew during premenopause (0.20% py) and the MT (0.35% py) (each non-zero, P < 0.05; not statistically different from each other) and decelerated to zero slope in postmenopause. Results are for the White referent; there were statistically significant differences in some trajectories in Black and Japanese women. CONCLUSIONS: The MT is associated with the development of central adiposity. Waist or hip circumferences are less sensitive to changes in fat distribution.

Longitudinal Assessment of Physical Activity and Cognitive Outcomes Among Women at Midlife

JAMA Network Open · 2021 · 31 citations

• Gerontology
• Medicine
• Psychology

Importance: The increasing prevalence of cognitive decline, impairment, and dementia spurs intense interest in cognitive preservation strategies. Objective: To explore the longitudinal association between physical activity (PA) and cognitive performance among women at midlife. Design, Setting, and Participants: This cohort study is an analysis from the Study of Women's Health Across the Nation. Enrollment occurred from 1996 through 1997, and follow-up extended into 2017. Included individuals were those who had undergone cognitive measures during the first 3 cognitive test visits and had at least 1 additional cognitive measurement. Stroke prior to baseline was an exclusion, and observations were censored for subsequent stroke. Data were analyzed from June 2018 through August 2019. Exposures: Engaging in sport or exercise PA (self-reported). Main Outcomes and Measures: The Symbol Digit Modalities Test (SDMT) was used to assess cognitive processing speed. The East Boston Memory Test-Delayed (EBMT-D) was used to measure verbal episodic memory. The digit span backwards (DSB) test was used to evaluate working memory. Results: Among 1718 women with a median (range) observation time of 11.9 (0.60-13.5) years, the mean (SD) baseline age was 45.7 (2.5) years. From baseline through age 61 years, mean change in SDMT score was -0.20 annually (95% CI, -0.26 to -0.15; P < .001). After age 61 years, the mean change in SDMT was -0.51 yearly (95% CI, -0.54 to -0.41; P < .001). Beginning at age 58 years of the mean change in EBMT was -0.03 yearly (95% CI, -0.04 to -0.02; P < .001). Starting at age 61 years, mean (SD) change in DSB was -0.03 annually (95% CI, -0.04 to -0.01; P = .001). When adjusted for attrition and practice effect, PA was associated with higher concurrent SDMT and EBMT scores and a smaller decrease in SDMT score. For each unit increment in PA, there was a 0.36 increment in concurrent SDMT score (95% CI, 0.14 to 0.59; P = .002) and a 0.10 increment in concurrent EBMT score (95% CI, 0.05 to 0.15; P < .001). Greater PA was associated with a smaller annual mean decrease in SDMT score (0.06 yearly; 95% CI, 0.02 to 0.09; P = .001). After additional adjustment for demographic characteristics, menopause symptoms, hormone therapy use, and the presence of diabetes and hypertension, PA was not associated with trajectories (ie, levels or slopes) of any cognitive outcome. Conclusions and Relevance: This cohort study found no association between greater PA levels and cognitive outcomes among women in midlife, unlike cohort studies that begin observations at later ages, which may be associated with confounding by reverse causation (ie, cognitive decline associated with an outcome of lower PA levels).

Faster Lumbar Spine Bone Loss in Midlife Predicts Subsequent Fracture Independent of Starting Bone Mineral Density

The Journal of Clinical Endocrinology & Metabolism · 2021 · 21 citations

• Medicine
• Internal medicine

CONTEXT: Bone mineral density (BMD) decreases rapidly during menopause transition (MT), and continues to decline in postmenopause. OBJECTIVE: This work aims to examine whether faster BMD loss during the combined MT and early postmenopause is associated with incident fracture, independent of starting BMD, before the MT. METHODS: The Study of Women's Health Across the Nation, a longitudinal cohort study, included 451 women, initially premenopausal or early perimenopausal, and those transitioned to postmenopause. Main outcome measures included time to first fracture after early postmenopause. RESULTS: In Cox proportional hazards regression, adjusted for age, body mass index, race/ethnicity, study site, use of vitamin D and calcium supplements, and use of bone-detrimental or -beneficial medications, each SD decrement in lumbar spine (LS) BMD before MT was associated with a 78% increment in fracture hazard (P = .007). Each 1% per year faster decline in LS BMD was related to a 56% greater fracture hazard (P = .04). Rate of LS BMD decline predicted future fracture, independent of starting BMD. Women with a starting LS BMD below the sample median, and an LS BMD decline rate faster than the sample median had a 2.7-fold greater fracture hazard (P = .03). At the femoral neck, neither starting BMD nor rate of BMD decline was associated with fracture. CONCLUSION: At the LS, starting BMD before the MT and rate of decline during the combined MT and early postmenopause are independent risk factors for fracture. Women with a below-median starting LS BMD and a faster-than-median LS BMD decline have the greatest fracture risk.

Melatonin Patterns and Levels During the Human Menstrual Cycle and After Menopause

Journal of the Endocrine Society · 2020 · 23 citations

• Physiology
• Medicine
• Endocrinology

CONTEXT: Melatonin may play a role in the regulation of the human menstrual cycle and may decline with menopause and/or aging. OBJECTIVE: The objective of this work is to investigate the relations between melatonin and the menstrual cycle, menopause, and aging. METHODS: This was a cross-sectional and longitudinal analysis of 20 participants from the Study of Women's Health Across the Nation (SWAN) Daily Hormone Study (DHS). The outcome measure was first-morning urine assay of 6-sulfatoxymelatonin (aMT6s), a gauge of melatonin. For each participant, aMT6s was measured daily during one premenopausal cycle with evidence of luteal activity (ELA) and one postmenopausal collection with no evidence of luteal activity (NELA). RESULTS: = .0002). CONCLUSIONS: This study confirms a late luteal melatonin rise, likely signaled by progesterone, which may influence menstrual cycle pacemaker control. Melatonin declined from premenopause to postmenopause. A high correlation between menopause transition stage and age precludes distinction between the influences of ovarian and chronological aging.

Antimullerian Hormone and Impending Menopause in Late Reproductive Age: The Study of Women’s Health Across the Nation

The Journal of Clinical Endocrinology & Metabolism · 2020 · 91 citations

• Medicine
• Gynecology
• Demography

BACKGROUND: A test that helps predict the time to the final menstrual period (FMP) has been sought for many years. OBJECTIVE: To assess the ability of antimullerian hormone (AMH) measurements to predictions the time to FMP. DESIGN: Prospective longitudinal cohort study. SETTING: The Study of Women's Health Across the Nation. PARTICIPANTS AND MEASUREMENTS: AMH and FSH were measured in 1537 pre- or early perimenopausal women, mean age 47.5 ± 2.6 years at baseline, then serially until 12 months of amenorrhea occurred. AMH was measured using a 2-site ELISA with a detection limit of 1.85 pg/mL. MAIN OUTCOME MEASURE: Areas under the receiver operating curves (AUC) for AMH-based and FSH-based predictions of time to FMP, stratified by age. Probabilities that women would undergo their FMP in the next 12, 24, or 36 months across a range of AMH values were assessed. RESULTS: AUCs for predicting that the FMP will occur within the next 24 months were significantly greater for AMH-based than FSH-based models. The probability that a woman with an AMH <10 pg/mL would undergo her FMP within the next 12 months ranged from 51% at h<48 years of age to 79% at ≥51 years. The probability that a woman with an AMH >100 pg/mL would not undergo her FMP within the next 12 months ranged from 97% in women <48 years old to 90% in women ≥51 years old. CONCLUSIONS: AMH measurement helps estimate when a woman will undergo her FMP, and, in general, does so better than FSH.

The Menopause Transition and Cognition

JAMA · 2020 · 87 citations

• Medicine
• Gerontology
• Clinical psychology

This JAMA Insights article summarizes the subjective cognitive problems experienced by some women during perimenopause (menopausal transition) and provides guidance to physicians on how to effectively answer patients’ questions and recognize when these symptoms may require clinical intervention.