Early Perimenopause Research Articles

Vasomotor Symptom Prevalence Is Associated with Polymorphisms in Sex Steroid–Metabolizing Enzymes and Receptors

The relation of single nucleotide polymorphisms (SNPs) of genes involved in estrogen function to vasomotor symptoms (VMS) has been inadequately explored. We evaluated SNPs in sex steroid–metabolizing genes and estrogen receptors (ERs) for their association with VMS (hot flashes, night sweats, and/or cold sweats) reported by women who were premenopausal or in early perimenopause at baseline. The study population was drawn from participants in the Study of Women’s Health Across the Nation (SWAN). African American, Caucasian, Chinese, and Japanese women, 42 to 52 years of age at baseline, who were enrolled in the longitudinal, community-based cohort of SWAN provided questionnaire, interview, weight and height measurements, and serum samples through the sixth annual visit. SNPs associated with the sex steroid hormone pathway were genotyped and available for 1,538 participants. These SNPs were associated with reporting VMS ≥6 days compared with <6 days in the past 2 weeks using race/ethnicity–specific repeated measures logistic regression models. Participants were on average 46 years old at baseline. The prevalence of VMS reporting increased in all racial/ethnic groups from baseline to the sixth annual follow-up visit. After adjustment for covariates, several SNPs encoding genes responsible for estrogen metabolism and ERs were associated with decreased odds of reporting VMS, including the CYP1B1 rs1056836 GC genotype in African American women; 17HSD rs615942 TG, 17HSD rs592389 TG, and 17HSD rs2830 AG genotypes in Caucasian women; and the CYP1A1 rs2606345 AC genotype in Chinese women. We identified race/ethnicity–specific associations between VMS reporting and specific polymorphisms for sex steroid–metabolizing enzymes and sex steroid receptors. Clarification of the mechanisms of the associations and confirmation in other populations is warranted.

Inflammatory Markers and Cardiovascular Risk in Healthy Polish Women across the Menopausal Transition

Cessation of ovarian function and sex hormone deficiency are associated with metabolic disorders that increase the risk of cardiovascular disease in women after menopause (1)(2). Changes in sex steroids may influence inflammatory processes and lipid metabolism during the menopausal transition. The status of estrogen in women at early perimenopause is similar to that of premenopause, whereas decreased estradiol is more likely in late perimenopause (3–11 months of amenorrhea) (3). Several studies have demonstrated that lipid concentrations, body weight, blood pressure, and insulin resistance increase after menopause and that endothelial function is impaired (4)(5)(6)(7). Recent data indicate that chronic inflammation may lead to atherosclerosis in healthy populations. It has been suggested that systemic markers of inflammation such as C-reactive protein (CRP) and interleukin-6 (IL-6) are important predictors of cardiovascular risk, and measurement of their concentrations may increase the predictive value of traditional lipid screening (8)(9). CRP assayed by high-sensitivity methods enables the evaluation of low-grade inflammation in early atherosclerosis. Rifai et al. (10)(11) recently proposed algorithms for the prediction of cardiovascular disease risk using CRP and total cholesterol/HDL-cholesterol (TC/HDL-C) or LDL-cholesterol (LDL-C) values. We investigated the relationship between hormonal status and cardiovascular risk assessed by inflammatory markers and traditional laboratory variables in women during menopausal transition. Our study included 80 early perimenopausal [PERI; mean (SD) age, 47 (3) years] and 78 postmenopausal [POST; mean age (SD), 53 (4) years] healthy nonsmoking women. The PERI women had irregular menses during the previous 12 months and at least one climacteric symptom (hot flashes, night sweats, vaginal dryness, sleeping difficulties, or mood swings). The POST women were divided into 2 groups: 40 early-POST (1–5 years without menses) and 38 late-POST (6–10 years without menses). None of …

Hemostatic Factors and Estrogen during the Menopausal Transition

It has been speculated that gender differences in cardiovascular disease (CVD) mortality can be attributed to the effects of estrogens on inflammation and hemostatic marker profiles. Therefore, we evaluated endogenous hormone concentrations, menopause transition stages, and adoption of exogenous hormone use in relation to hemostatic and inflammation marker concentrations in women. Longitudinally, we studied 3302 participants from the Study of Women's Health Across the Nation, aged 42-52 yr at baseline and self-identified as African-American (28%), Caucasian (47%), Chinese (8%), Hispanic (8%), or Japanese (9%). Serum samples from baseline and years 2001, 2003, and 2005 were assayed for estradiol and FSH. Hormone concentrations were related to CVD markers, including fibrinogen, factor VII-c, plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator, and human serum C-reactive protein (hsCRP). Lower estradiol levels were associated with higher levels of PAI-1 and tissue plasminogen activator, but there were no significant relationships with fibrinogen, factor VII-c, or hsCRP. Higher FSH concentrations were associated with higher PAI-1 and factor VII levels, but lower fibrinogen and hsCRP levels. Transitions from premenopause and early perimenopause to postmenopause were not associated with significant differences in levels of hemostatic factors. The hsCRP concentrations were approximately 25% higher, and the PAI-1 concentrations approximately 20% lower among women who initiated hormone therapy, compared with nonusers. Endogenous estrogens may reduce CVD risk via modulation of fibrinolytic factors, but not coagulation or inflammatory markers. Notably, conclusions derived from studies of exogenous hormones and CVD risk may not parallel or explain the effects of endogenous hormones or perimenopausal hormone changes on CVD risk.

Correlates of sexual function among multi-ethnic middle-aged women: results from the Study of Women's Health Across the Nation (SWAN).

To examine sexual function in a cohort of Baby Boomer women of diverse racial/ethnic backgrounds; to compare differences between pre-and early perimenopausal women; and to identify sociodemographic, health-related, and psychosocial (including psychological, behavioral, and relationship) factors related to sexual function. Six domains of sexual function were studied in 3,167 women in the baseline cohort of the Study of Women's Health Across the Nation (SWAN). Participants were 42 to 52 years old, pre-or early perimenopausal, and not using hormones. The study sample included non-Hispanic white, African American, Hispanic, Chinese, and Japanese women. Early perimenopausal women reported greater pain with intercourse than premenopausal women (P = 0.01), but the two groups did not differ in frequency of sexual intercourse, desire, arousal, or physical or emotional satisfaction. Variables having the greatest association across all outcomes were relationship factors, the perceived importance of sex, attitudes toward aging, and vaginal dryness. Despite controlling for a wide range of variables, we still found ethnic differences for arousal (P < 0.0001), pain (P = 0.03), desire (P < 0.0001), and frequency of sexual intercourse (P = 0.0003). African American women reported higher frequency of sexual intercourse than white women; Hispanic women reported lower physical pleasure and arousal. Chinese women reported more pain and less desire and arousal than the white women, as did the Japanese women, although the only significant difference was for arousal. Relationship variables, attitudes toward sex and aging, vaginal dryness, and cultural background have a greater impact on most aspects of sexual function than the transition to early perimenopause.

Correlates of sexual function among multi-ethnic middle-aged women: results from the Study of Women's Health Across the Nation (SWAN)

To examine sexual function in a cohort of Baby Boomer women of diverse racial/ethnic backgrounds; to compare differences between pre-and early perimenopausal women; and to identify sociodemographic, health-related, and psychosocial (including psychological, behavioral, and relationship) factors related to sexual function. Six domains of sexual function were studied in 3,167 women in the baseline cohort of the Study of Women's Health Across the Nation (SWAN). Participants were 42 to 52 years old, pre-or early perimenopausal, and not using hormones. The study sample included non-Hispanic white, African American, Hispanic, Chinese, and Japanese women. Early perimenopausal women reported greater pain with intercourse than premenopausal women (P = 0.01), but the two groups did not differ in frequency of sexual intercourse, desire, arousal, or physical or emotional satisfaction. Variables having the greatest association across all outcomes were relationship factors, the perceived importance of sex, attitudes toward aging, and vaginal dryness. Despite controlling for a wide range of variables, we still found ethnic differences for arousal (P < 0.0001), pain (P = 0.03), desire (P < 0.0001), and frequency of sexual intercourse (P = 0.0003). African American women reported higher frequency of sexual intercourse than white women; Hispanic women reported lower physical pleasure and arousal. Chinese women reported more pain and less desire and arousal than the white women, as did the Japanese women, although the only significant difference was for arousal. Relationship variables, attitudes toward sex and aging, vaginal dryness, and cultural background have a greater impact on most aspects of sexual function than the transition to early perimenopause.

031: Percent Versus total Area of Mammographic Density in Pre- or Early Perimenopausal Caucasian, Chinese, Japanese and African American Women

031: Percent Versus total Area of Mammographic Density in Pre- or Early Perimenopausal Caucasian, Chinese, Japanese and African American Women

Persistent Mood Symptoms in a Multiethnic Community Cohort of Pre- and Perimenopausal Women

To further our understanding of the relation between mood and menopause, the authors examined 1) the association between persistent mood symptoms and menopausal status and 2) factors that increase a woman's vulnerability to an overall dysphoric mood during the early perimenopausal period. The sample consisted of an ethnically diverse community cohort of 3,302 pre- and early perimenopausal women aged 42-52 years who were participants in the Study of Women's Health Across the Nation, an ongoing US multisite longitudinal study of menopause and aging. At study entry (1995-1997), women reported information on recent menstrual regularity and premenstrual symptoms, as well as on sociodemographic, symptom, health, sleep, psychosocial, and lifestyle variables. Rates of persistent mood symptoms were higher among early perimenopausal women (14.9%-18.4%) than among premenopausal women (8%-12%). In analyses adjusting for major covariates and confounders, early perimenopausal women had higher odds of irritability, nervousness, and frequent mood changes but not of feeling "blue." The effect of being early perimenopausal on overall dysphoric mood was greatest among women with an educational level of less than high school graduation. These findings suggest that persistent mood symptoms and overall dysphoric mood are associated with the early perimenopause, particularly among women with lower educational attainment.

The association of endogenous hormone concentrations and bone mineral density measures in pre- and perimenopausal women of four ethnic groups: SWAN.

We evaluated bone mineral density (BMD), hormone concentrations and menstrual cycle status to test the hypothesis that greater variations in reproductive hormones and menstrual bleeding patterns in mid-aged women might engender an environment permissive for less bone. We studied 2336 women, aged 42-52 years, from the Study of Women's Health Across the Nation (SWAN) who self-identified as African-American (28.2%), Caucasian (49.9%), Japanese (10.5%) or Chinese (11.4%). Outcome measures were lumbar spine, femoral neck and total hip BMD by dual-energy X-ray densitometry (DXA). Explanatory variables were estradiol, testosterone, sex hormone binding globulin (SHBG) and follicle stimulating hormone (FSH) from serum collected in the early follicular phase of the menstrual cycle or menstrual status [premenopausal (menses in the 3 months prior to study entry without change in regularity) or early perimenopause (menstrual bleeding in the 3 months prior to study entry but some change in the regularity of cycles)]. Total testosterone and estradiol concentrations were indexed to SHBG for the Free Androgen Index (FAI) and the Free Estradiol Index (FEI). Serum logFSH concentrations were inversely correlated with BMD (r = -10 for lumbar spine [95% confidence interval (CI): -0.13, -0.06] and r = -0.08 for femoral neck (95% CI: -0.11, -0.05). Lumbar spine BMD values were approximately 0.5% lower for each successive FSH quartile. There were no significant associations of BMD with serum estradiol, total testosterone, FEI or FAI, respectively, after adjusting for covariates. BMD tended to be lower (p values = 0.009 to 0.06, depending upon the skeletal site) in women classified as perimenopausal versus premenopausal, after adjusting for covariates. Serum FSH but not serum estradiol, testosterone or SHBG were significantly associated with BMD in a multiethnic population of women classified as pre- versus perimenopausal, supporting the hypothesis that alterations in hormone environment are associated with BMD differences prior to the final menstrual period.

Ethnic variation in bone density in premenopausal and early perimenopausal women: effects of anthropometric and lifestyle factors.

Bone mineral density (BMD) and fracture rates vary among women of differing ethnicities. Most reports suggest that BMD is highest in African-Americans, lowest in Asians, and intermediate in Caucasians, yet Asians have lower fracture rates than Caucasians. To assess the contributions of anthropometric and lifestyle characteristics to ethnic differences in BMD, we assessed lumbar spine and femoral neck BMD by dual-energy x-ray absorptiometry in 2277 (for the lumbar spine) and 2330 (for the femoral neck) premenopausal or early perimenopausal women (mean age, 46.2 yr) participating in the Study of Women's Health Across the Nation. Forty-nine percent of the women were Caucasian, 28% were African-American, 12% were Japanese, and 11% were Chinese. BMDs were compared among ethnic groups before and after adjustment for covariates. Before adjustment, lumbar spine and femoral neck BMDs were highest in African-American women, next highest in Caucasian women, and lowest in Chinese and Japanese women. Unadjusted lumbar spine and femoral neck BMDs were 7-12% and 14-24% higher, respectively, in African-American women than in Caucasians, Japanese, or Chinese women. After adjustment, lumbar spine and femoral neck BMD remained highest in African-American women, and there were no significant differences between the remaining groups. When BMD was assessed in a subset of women weighing less than 70 kg and then adjusted for covariates, lumbar spine BMD became similar in African-American, Chinese, and Japanese women and was lowest in Caucasian women. Adjustment for bone size increased values for Chinese women to levels equal to or above those of Caucasian and Japanese women. Among women of comparable weights, there are no differences in lumbar spine BMD among African-American, Chinese, and Japanese women, all of whom have higher BMDs than Caucasians. Femoral neck BMD is highest in African-Americans and similar in Chinese, Japanese, and Caucasians. These findings may explain why Caucasian women have higher fracture rates than African-Americans and Asians.

Ethnic Variation in Bone Turnover in Pre- and Early Perimenopausal Women: Effects of Anthropometric and Lifestyle Factors

Bone mineral density (BMD) and fracture rates vary among women of differing ethnicities. Little is known, however, about ethnic variation in bone turnover. We measured serum osteocalcin (OC) and urinary N-telopeptide of type I collagen (NTX) levels in 2313 pre- or early perimenopausal women who were Caucasian (n = 1140), African-American (n = 651), Chinese (n = 247), or Japanese (n = 275) and were participating in the Study of Women’s Health Across the Nation. Serum OC and urinary NTX levels were compared before and after adjustment for a series of lifestyle and anthropometric variables that can affect bone turnover. Unadjusted serum OC levels were highest in Caucasian women (P < 0.001 vs. all other groups), higher in African-American than Chinese women (P = 0.006), and similar in Chinese and Japanese women (P = 0.203) and African-American and Japanese women (P = 0.187). Unadjusted serum OC levels were 11–24% higher in Caucasians than in the other groups. Adjustment for covariates did not alter the ethnic pattern of serum OC levels. Unadjusted urinary NTX levels were statistically significantly higher in Caucasian and African-American women than in Chinese women (P < 0.001) for both comparisons). Unadjusted urinary NTX levels were higher in Caucasian than in Japanese women (P = 0.071) and higher in Japanese than in Chinese women (P = 0.055), but these differences were of borderline statistical significance. Unadjusted urinary NTX levels were 9–18% higher in African-Americans and Caucasians than in the other groups. Among Caucasians, there were significant geographic regional variations in both serum OC and urinary NTX levels, with higher levels in women from the Northeast and the Midwest than in women from California. These data demonstrate significant ethnic differences in bone turnover in pre- and early perimenopausal women. Although these differences in adult bone turnover may explain some of the known ethnic variation in BMD, ethnic patterns of adult bone turnover do not parallel patterns of BMD. Other factors, such as differences in bone accretion, are likely responsible for much of the ethnic variation in adult BMD.

Ethnic variation in bone turnover in pre- and early perimenopausal women: effects of anthropometric and lifestyle factors.

Bone mineral density (BMD) and fracture rates vary among women of differing ethnicities. Little is known, however, about ethnic variation in bone turnover. We measured serum osteocalcin (OC) and urinary N-telopeptide of type I collagen (NTX) levels in 2313 pre- or early perimenopausal women who were Caucasian (n = 1140), African-American (n = 651), Chinese (n = 247), or Japanese (n = 275) and were participating in the Study of Women's Health Across the Nation. Serum OC and urinary NTX levels were compared before and after adjustment for a series of lifestyle and anthropometric variables that can affect bone turnover. Unadjusted serum OC levels were highest in Caucasian women (P < 0.001 vs. all other groups), higher in African-American than Chinese women (P = 0.006), and similar in Chinese and Japanese women (P = 0.203) and African-American and Japanese women (P = 0.187). Unadjusted serum OC levels were 11-24% higher in Caucasians than in the other groups. Adjustment for covariates did not alter the ethnic pattern of serum OC levels. Unadjusted urinary NTX levels were statistically significantly higher in Caucasian and African-American women than in Chinese women (P < 0.001) for both comparisons). Unadjusted urinary NTX levels were higher in Caucasian than in Japanese women (P = 0.071) and higher in Japanese than in Chinese women (P = 0.055), but these differences were of borderline statistical significance. Unadjusted urinary NTX levels were 9-18% higher in African-Americans and Caucasians than in the other groups. Among Caucasians, there were significant geographic regional variations in both serum OC and urinary NTX levels, with higher levels in women from the Northeast and the Midwest than in women from California. These data demonstrate significant ethnic differences in bone turnover in pre- and early perimenopausal women. Although these differences in adult bone turnover may explain some of the known ethnic variation in BMD, ethnic patterns of adult bone turnover do not parallel patterns of BMD. Other factors, such as differences in bone accretion, are likely responsible for much of the ethnic variation in adult BMD.

Ethnic Variation in Bone Density in Premenopausal and Early Perimenopausal Women: Effects of Anthropometric and Lifestyle Factors

Ethnic Variation in Bone Density in Premenopausal and Early Perimenopausal Women: Effects of Anthropometric and Lifestyle Factors

A prospective population-based study of menopausal symptoms

Objective: To identify symptoms that change in prevalence and severity during midlife and evaluate their relationships to menopausal status, hormonal levels, and other factors. Methods: In a longitudinal, population-based study of 438 Australian-born women observed for 7 years with an 89% retention rate, 172 advanced from premenopause to perimenopause or postmenopause. Annual measures included a 33-item symptom check list; psychosocial, lifestyle, and health-related factors; menstrual status; hormone usage; and blood levels of follicle-stimulating hormone and estradiol (E2). Results: Increasing from early to late perimenopause were the number of women who reported five or more symptoms (+14%), hot flushes (+27%), night sweats (+17%) and vaginal dryness (+17%) (all P < .05). Breast soreness-tenderness decreased with the menopausal transition (−21%). Trouble sleeping increased by +6%. The major change in prevalence was from early to late perimenopause, except for insomnia, which showed a gradual increase. Those variables most related to onset of hot flushes were number of symptoms at early perimenopause ( P < .05), having an unskilled or no occupation ( P < .05), more than 10 pack-years of smoking ( P < .01), and decreased E2 ( P < .01). The onset of night sweats increased with the change in E2 ( P < .05). The onset of vaginal dryness decreased with more years of education ( P < .05). Trouble sleeping was predicted by prior lower well-being ( P < .01), belief at baseline that women with many interests hardly notice menopause ( P < .01), and hot flushes ( P < .01). Conclusion: Although middle-aged women are highly symptomatic, the symptoms that appear to be specifically related to hormonal changes of menopausal transition are vasomotor symptoms, vaginal dryness, and breast tenderness. Insomnia reflected bothersome hot flushes and psychosocial factors.

Longitudinal patterns and correlates of hormone replacement therapy use in middle-aged women.

Patterns of hormone replacement therapy (HRT) use over time and predictors of initiating or discontinuing use were examined in a longitudinal study. A cohort of 2,425 women aged 45-55 years identified from a population-based random survey in Massachusetts in 1981-1982 was followed by six telephone interviews, 9 months apart. Cohort participants were either premenopausal (66.8%) or in early perimenopause (33.2%). During the study, prevalence of use was low overall (12.3%) and was considerably higher for surgical menopause (45%) than for peri- (9.3%), natural (4.5%), or premenopause (1.5%). Predictors of HRT uptake and discontinuation (from time t - 1 to time t) were examined by repeated-measures logistic regression, stratified by surgical status. For surgical menopause, the only significant predictor of HRT uptake was recent surgery (odds ratio = 4.4; 95% confidence interval 2.73-7.22), while for nonsurgical subjects, menopausal status (primarily perimenopause), prior use of HRT, health care utilization, hot flashes, alcohol consumption, regular exercise, and leaner body mass were all significant predictors of uptake. Discontinuing HRT was inversely associated with surgical and perimenopause and positively related to prior short-term use and health care utilization. Nonsurgical HRT users had a somewhat more favorable cardiovascular risk profile than did nonusers.