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The menopause transition
Abstract
The menopause transition is a period of life during which a series of dynamic changes in physiology are taking place. There seems to be a transient increase in symptoms of many types, which are occasionally severe. There is a disproportionate burden of morbidity that seems to accrue to women of high body mass index and low socioeconomic status. Moreover, there are ethnic differences in hormones and symptoms that may reflect either basic biologic variation in hormone receptors and actions or the different social milieu that women in different ethnic groups experience. Current medical management of the perimenopause should include screen-ing for general health maintenance, avoidance of weight gain, and a holistic approach to symptoms.
... Despite this improved quantity of life, side effects from breast cancer treatment can decrease quality of life. Unpleasant symptoms are often experienced secondary to consequences of diagnosis and the life-extending treatments of chemotherapy, hormonal therapy, hormone agonists, and ovarian ablation (Santoro, 2005;Woods & Mitchell, 2005). ...
... Urogenital atrophy is a constellation of symptoms potentially affecting many biopsychosocial aspects of a woman, and possibly her partner. Unpleasant symptoms are divided into three domains: urologic, genital, and sexual, including urinary symptoms of urgency, urge incontinence, stress incontinence, dysuria/burning with urination, pressure/frequency, recurrent urinary tract infections, and dryness; genital symptoms of bleeding, burning, discharge/vaginitis, itching, irritation, soreness/tenderness, and dryness; and sexual symptoms of dyspareunia/pain with intercourse, decreased sexual satisfaction, difficulty in sexual arousal, loss of interest in sexual activity/decreased libido, vaginal discharge, decreased closeness with partner, and dryness (Ballagh, 2005;Castelo-Branco, Cancelo, Villero, Nohales, & Julia, 2005;McKenna, Whalley, Renck-Hooper, Carlin, & Doward, 1999;Oskay, Beji, & Yalcin, 2005;Santoro, 2005;Willhite & O"Connell, 2001;Woods & Mitchell, 2005). ...
... Urogenital atrophy is related to hormonal changes of the perimenopausal and menopausal periods in the female life cycle. The menopausal transition typically starts in a woman"s forties, with median age of final menstrual period at 51.4 years (Santoro, 2005). ...
... Menstrual cycles in late perimenopausal women are characterized by increased FSH, decreased inhibin B (Figure 2), and irregularly short and long cycle lengths [16]. Estradiol levels of menopausal women vary similarly till the last menstrual period (LMP) [17,18]. Women develop a permanent condition of hypogonadism and hypergonadotropism (elevated FSH and LH) by the LMP. ...
... Santoro et al. [17] 2004 A number of dynamic changes in physiology occur throughout the menopause transition stage of life. ...
Menopause, when menstrual cycles stop, is brought on by a decline in the level of the hormones progesterone and oestrogen synthesised by the ovaries. Menopause is an unavoidable stage of a female's lifecycle, but because experiences differ for every woman, several women require health care aid to manage their health problems. The physiological variations that take place at various periods of the reproducing age, along with the kind and timing of menopause, are components that are frequently associated with a greater threat of cardiometabolic illness. The most researched associations between menopause and cardiometabolic health are reduced levels of ovarian estrogen synthesis and excessive amounts of androgen during the onset of menopause. Although testosterone and oestrogens have differing effects on adipocyte physiology, it is debatable how important oestrogens are for the emergence of metabolic disorders following menopause. The control of adipocyte differentiation by the brain as well as potential roles of oestrogen and endocrine disruptors chemicals are reviewed in this systematic review of the subject. In general, women had a greater frequency of metabolic syndrome compared to men. Female metabolism was significantly impacted by overt hyperthyroidism and subclinical hypothyroidism. Osteoporosis is another medical condition that menopausal women may experience. Estrogen deprivation is the main contributor to osteoporosis in menopausal women. The regular cycle of bone turnover is disrupted by the decrease in estrogen secretion, which boosts osteoclastic resorption activity while decreasing osteoblastic activity. The entire article assesses and provides information on all the changes in a woman's life after menopause.
... Menopause progression, decreased physical activity and increased oxidative stress are associated with increased risk of cardiovascular disease in women, 1 promoting changes in body mass and hormonal profile directly related to the regulation of the antioxidant system. 2 The progressive increase in lipid peroxidation 3 and redox state [4][5][6] can partially explain the increased cardiovascular risk in this population. ...
... Menopause is accompanied by increased risk for diseases associated with oxidative stress. 2,4 Although the beneficial effects of exercise on antioxidant system in postmenopausal women have been reported, [39][40][41] we found no studies evaluating different volumes of resistance and aerobic exercise and its effects on oxidative stress markers in this population. We used different exercise approaches in our study since both modalities are required for health promotion in this population, aiming to match the recommendations of 30 minutes of daily aerobic exercise with intensity of 50% to 85% of reserve oxygen consumption and at least 2 weekly sessions of resistance exercise load intensity around 65% to 75% of 1RM, which would be equivalent to 15RM. ...
Introduction:
Since exercise increases the production of reactive oxygen species in different tissues, the objective of this study is to evaluate, compare and correlate the acute effects of aerobic and resistance exercise in circulatory markers of oxidative stress and acylated ghrelin (AG) in postmenopausal women.
Methods:
Ten postmenopausal women completed different protocols: a control session (CON), an aerobic exercise session (AERO); and a single-set (SSR) or three-set (MSR) resistance exercise protocol.
Results:
After exercise, both MSR (p=0.06) and AERO (p=0.02) sessions showed significant increased lipid peroxidation compared to baseline levels. CON and SSR sessions showed no differences after exercise. No differences were found between sessions at any time for total glutathione, glutathione dissulfide or AG concentrations.
Conclusions:
Exercise significantly increased lipid peroxidation compared to baseline values. As pro oxidant stimuli is necessary to promote chronic adaptations to the antioxidant defenses induced by exercise, our findings are important to consider when evaluating exercise programs prescription variables aiming quality of life in this population.
... Variability in ovarian function occurs during the menopausal transition (MT) and results in the fluctuation of oestrogen concentration levels that are associated with a drop in progesterone and a progressive increase in follicle-stimulating hormone (FSH) levels [1][2][3][4]. Approximately 80% of MT women experience climacteric symptoms(CS), such as hot flushes, sweating, mood changes, decreased libido, vaginal dryness, and sexual avoidance, which affect the quality of life (QoL) and require treatment [3,5]. ...
... Variability in ovarian function occurs during the menopausal transition (MT) and results in the fluctuation of oestrogen concentration levels that are associated with a drop in progesterone and a progressive increase in follicle-stimulating hormone (FSH) levels [1][2][3][4]. Approximately 80% of MT women experience climacteric symptoms(CS), such as hot flushes, sweating, mood changes, decreased libido, vaginal dryness, and sexual avoidance, which affect the quality of life (QoL) and require treatment [3,5]. ...
To evaluate the efficacy, safety and tolerability of Tibolone use during the menopausal transition (MT).
Sixty-five healthy women aged 40-55 years (48.5 ± 3.5 years) were recruited for a randomized, double-blind controlled trial. Thirty participants were recruited to receive oral Tibolone 2.5 mg/day - Tibolone Group (TG), and 35 participants were assigned to the Placebo Group (PG), which received one capsule of lactose/day. Both groups were treated for 12 consecutive weeks. The Blatt-Kupperman Menopausal Index (KMI) and the Greene Climacteric Scale (GCS) were used. The glycaemic and lipid profiles, biochemical measures of hepatic function and endometrial thickness were measured for safety. A daily registry of complaints related to the treatment was maintained, and anthropometric measures were obtained to assess tolerability.
A total of 57 women completed the study. After 12 weeks of Tibolone use, the total score and percentage of the KMI and GCS were significantly decreased compared to baseline, which reflected the efficacy of the treatment of climacteric symptoms. The improvement in blood biochemistry, endometrial atrophy and maintenance of the anthropometrical measures reflected the safety of Tibolone use. The absence of serious side effects demonstrated good tolerability for Tibolone use.
The results showed good efficacy, tolerability and safety of Tibolone use during the MT.
... The previously held belief that the perimenopause is characterized by a gradual decline in estrogen levels with rising follicle-stimulating hormone (FSH) 51 has been challenged by current research indicating that serum estradiol (or urinary estrogen excretion) actually increases slowly with increasing age, 34,[52][53][54][55][56] and declines only from about 2 years prior to final menses. 57 Research on the inhibins has helped to clarify the underlying mechanism. ...
... The falling inhibin levels (especially INH-B), resulting from the declining antral follicle count as women age, 59 allows the gradual rise in FSH, which drives increased estradiol secretion. 56,58,60 This may lead to accelerated follicle development and occasions of multiple follicles developing at once, and hence give rise, on occasion, to markedly raised estradiol concentrations in perimenopausal women. 27,34,52 Lower than normal levels of estradiol have been found in late-perimenopausal women who had experienced 3 months' amenorrhea 60 and in late-perimenopausal women during anovulatory cycles, 61 and in cycles with an elongated ''lag period'' between the menstrual phase and the onset of the follicular phase. ...
The origin of the current practice of administering Vitex agnus-castus in menopause-related complaints is uncertain, but appears to be relatively recent. Here we review the evidence for this application of Vitex based on evidence from pharmacological studies and clinical research.
The mechanisms of potential relevance in the context of menopause are explored with reference to the current understanding of the endocrinology and neuroendocrinology of menopause and associated symptoms.
We conclude that, while evidence from rigorous randomized controlled trials is lacking for the individual herb in this context, emerging pharmacological evidence supports a role for V. agnus-castus in the alleviation of menopausal symptoms and suggests that further investigation may be appropriate.
... Districtlevel analysis revealed early natural menopause in northeastern districts and surgical menopause in the GeoJournal (2024) menopause) or be induced by a surgical procedure (surgical or artificial menopause). While menopause is a biological process, various socio-cultural and demographic factors, particularly in a diverse country like India, may impact the age at which women experience menopause (Ahuja, 2016;Loh et al., 2005;Santoro & Chervenak, 2004). Numerous studies have identified socio-demographic, nutritional, and fertility-related variables as crucial determinants of menopause (Mozumdar & Agrawal, 2015;Syamala & Sivakami, 2005). ...
In India, the increasing life expectancy among women highlights the likelihood of more women reaching menopause. However, the public health programs often overlook women in this age group, focusing on reproductive age groups. Therefore, it's crucial to explore different dimensions of menopause, including geographical disparities and age. So far, there's been no examination of estimation of mean menopausal age or district-level menopausal variations at national level. This study categorized menopause into natural and surgical menopause, allowing separate analysis. Using data from NFHS-5 and LASI wave one, it employed John Hajnal’s SMAM technique to estimate the mean age at natural menopause. Results showed an average menopausal age of 46 years in India, with Bihar lowest at 44 years and Kerala highest at 47.6 years. Natural premature menopause was found to be highest in Karnataka, while surgical was highest in Bihar. District-level analysis revealed early natural menopause in northeastern districts and surgical menopause in the districts of Bihar, Andhra Pradesh, and Telangana. Women residing in rural areas, those with lower educational levels, multiple pregnancies and obese were found to have higher odds of experiencing early menopause. The odds were found to be lower for women who had ever used any contraceptive methods. The study highlights the need to reconsider health policies for women post-reproductive age, particularly in regions with high prevalence of early menopause. It also suggests that proper education and reducing the number of pregnancies by adopting family planning methods may also help reduce early menopause. It further emphasizes the importance of identifying and targeting vulnerable populations such as those from rural and uneducated background; and ensuring counselling and informed choice, especially regarding hysterectomy before age 40.
... Interestingly, in another study on postmenopausal women, endothelial function was significantly lower in ACE DD than in ACE II (Méthot et al., 2006). It has been shown that different ethnic groups may vary in age of menopause (Santoro and Chervenak, 2004), whereas menopause is closely associated with different hormones and factors such as ERFs (Kang et al., 2011), exerting different regulatory effects on FMD. Thus, it would be interesting to compare the difference in endothelial function in relation to menopause status, aging, and ACE D/I genotype between different ethnic groups. ...
Many studies have investigated the relationship between angiotensin-converting enzyme (ACE) D/I polymorphism and cardiovascular disease or endothelial dysfunction; however, hardly any of these studies has taken aging or menopause into consideration. Furthermore, despite that many studies have examined the regulatory effects of endothelial-released factors (ERFs) on endothelial function, no study has evaluated the relationship between ERFs and endothelial function with respect to ACE D/I polymorphism and menopause status. To answer these questions, 391 healthy Chinese women over a wide range of ages (22–75 years) were enrolled and divided into pre-menopause group and post-menopause group. After ACE D/I genotype being identified, the women were then classified into either DI/II or DD genotype. Flow-mediated dilatation (FMD) of brachial endothelium and plasma levels of ERFs: nitric oxide (NO), endothelin-1 (ET-1), and angiotensin II (Ang II) were measured. The results showed that frequencies of ACE D/I genotypes were in accordance with the Hardy-Weinberg equilibrium, and the frequency of I allele was higher than D allele. In pre-menopause group, FMD was significantly higher in women of DI/II than DD (P = 0.032), and age-dependent in both genotypes (DD, P = 0.0472; DI/II, P < 0.0001). In post-menopause group, FMD was similar between women of DI/II and DD, and age-dependent only in women of DI/II (P < 0.0001). In pre-menopause group, Ang II level was significantly higher in women of DD than DI/II (P = 0.029), and FMD was significantly correlated with all ERFs in women of DD (NO, P = 0.032; ET-1, P = 0.017; Ang II, P = 0.002), but only with Ang II in women of DI/II (P = 0.026). In post-menopause group, no significant difference was observed in any ERF between women of DI/II and DD, and FMD was only significantly correlated with ET-1 in women of DD (P = 0.010). In summary, FMD in women of DI/II was superior to DD in pre-menopause and more age-dependent than DD in post-menopause, and FMD was closely associated with ERFs. In conclusion, Chinese women of DI/II seem to have lower risk than DD in pre-menopause, but similar risk as DD in post-menopause in developing cardiovascular disease.
... The menopausal transition is associated with profound dynamic and critical changes of the reproductive tract, and in the hypothalamic-pituitary-ovarian axis, which have been well chronicled and matched with concomitant symptoms regarding the characteristics of menstrual cycle-the most important parameter in the new criteria of STRAW +10 (2012), which starts with the irregularities from stage-3b/-3a in the late reproductive age [1,2], and of all other organs and tissues of the women's body, biology and psychology through this time of life. There are ethnic differences in symptoms and hormones that may reflect either basic biologic variations in hormone receptors and actions or the different social milieus that women in different ethnic groups experience [3]. The highly prevalent menopausal symptoms are sufficiently bothersome to drive almost 90% of women to seek out their healthcare provider for advice on how to cope with it. ...
... Menopause progression leads to several changes in the hormonal profile, which exert impact on parameters related to Resting Metabolic Rate (RMR) and body composition, such as increased adipose tissue, increased central adiposity, and decreased lean mass, consequently increasing the risk of developing metabolic and cardiovascular diseases [1,2]. Thus, interventions based on the individual estimates of the energy requirements in terms of diet and exercise to determine an adequate energy balance should be recommended for health promotion in postmenopausal women [3]. ...
Objective
To compare resting metabolic rate values determined by indirect calorimetry with values estimated using different predictive equations in lean and overweight postmenopausal women.
Methods
Twenty-four women, who had stopped menstruating for at least two years, were subjected to anthropometric measurements and indirect calorimetry after 12-hour overnight fasting to determine, mathematically and experimentally, resting metabolic rate values.
Results
There was no difference in the indirect calorimetry values between the groups evaluated. Difference values of resting metabolic rate were obtained with all equations used. For the lean women, there was no difference between the values obtained by indirect calorimetry and those estimated using the equations proposed by Food and Agricultural Organization, Fredix, Lazzer, and Schofield. However, in the overweight group, the resting metabolic rate values estimated using the Institute of Medicine, Berstein and Owen equations were different from those obtained by indirect calorimetry.
Conclusion
This study suggests that differences in body composition in postmenopausal women influence the accuracy of predictive equations, demonstrating the need for more accurate estimation methods for resting metabolic rate in postmenopausal women with different body compositions.
... Menopause is one of the most striking events occurring during a women's life that holds intrinsic clinical and public health interest due to its related complications. It is considered an important marker of aging and health in women.[1,2]Increasing life expectancy results in an increase in postmenopausal women population worldwide. ...
Background
Identification of osteoporosis in women in order to prevent its related morbidity and mortality is considered a priority. Routine mammography is performed on all menopausal women as a screening tool. Determination of the relation between breast arterial calcification (BAC) on mammography and the bone density of this high-risk population could help us to determine those with osteoporosis. The aim of this study was to investigate the mentioned probable relation between BAC and osteoporosis.
Materials and Methods
In this cross-sectional study, menopausal women referred for annual screening mammography were enrolled. According to the results of mammography, they were classified into two groups: menopausal women with and without calcification of breast arteries. The selected women were referred for bone mineral density (BMD) evaluation by dual-energy x-ray absorptiometry (DXA). The results of BMD were compared between the two studied groups.
Results
In this study, BMD was measured in 43 and 45 menopausal women with and without BAC, respectively. After age adjustment the difference between BMD measurements were not statistically significantly different (P > 0.05). There was a significant negative correlation between age and lumbar (P = 0.002, r = -0.42) and hip bone (P = 0.000, r = -0.67) density in menopausal women with BAC.
Conclusion
The results of the current study indicated that there was no significant relationship between BAC and BMD in our studied population, but it seems that increasing age has an important role in both developing BAC and reducing BMD. For obtaining more conclusive results, further studies with larger sample sizes and considering the severity of BAC is recommended.
... risk factors in bladder symptom occurrence. 8,32 In addition, BMI has also been shown to influence reproductive stage, [33][34][35] and reproductive stage was a significant contributor in the regression model when also controlling for age, parity, diuretic use, race/ethnicity, and BMI. Previous studies similar to ours have described risk factors, such as parity, ethnicity, BMI, reproductive status, and age, to be associated with bladder symptoms in pre-and postmenopausal women. ...
Purpose:
Bladder symptoms are common in women and result in use of healthcare resources and poor quality of life. Bladder symptoms have been linked to age and menopause, but debate exists in the literature. This article examines factors associated with bladder symptoms and compares women in late reproductive stage with those in menopausal transition.
Materials and methods:
We analyzed cross-sectional data from a prospective cohort study of midlife women (mean age, 48; range, 44-54 years) in northern California. The sample consisted of 158 women in late reproductive stage or menopause transition. Assessments included anthropometrics, menstrual cycle lengths and symptoms, urine samples for follicle-stimulating hormone level, and self-reported health perception and depressive symptoms. Analyses included descriptive bivariate statistics, group comparisons, and regression models.
Results:
The most common bladder symptoms were nocturia (72%) at least once per night and urinary incontinence (50%) at least once per week. Incontinence was less prevalent in African American women compared to European Americans and Latinas (p = 0.001) and more prevalent in late reproductive stage than in menopause transition (p = 0.024). Controlling for age, women in late reproductive stage were more likely to report nocturia compared to those in menopause transition. Reproductive stage (p = 0.016), higher body mass index (p = 0.007), and race (p = 0.017) contributed to the variance in weekly nighttime urinary frequency.
Conclusion:
Bladder symptoms were associated with reproductive stage. Women in late reproductive stage were more likely to experience nocturia and incontinence than those in menopause transition. The higher rates of nocturia and incontinence in late reproductive stage are intriguing. Future studies should include analysis of pelvic organ prolapse degree and other structural differences.
... Multiple physiologic changes that occur during the menopausal transition result from reduced ovarian reserve and reduced numbers of gonadotropin responsive follicles. Menstrual cycles in late perimenopausal women are characterized by increased FSH, decreased inhibin B, and irregularly short and long cycle lengths [10]. Until the time of the last menstrual period (LMP), estradiol levels are equally variable in perimenopausal women. ...
Sexuality is an important component in the lives of menopausal women. Despite the importance of sexual function in menopausal women, sexual dysfunction increases with age. Age-related decline in sexual function may significantly reduce quality of life, making recognition of sexual dysfunction by physicians important for getting menopausal women effective care. Sexual dysfunction can result from multiple etiologies including psychosocial factors, medication side effects, vulvovaginal atrophy, chronic illness, or hypoactive sexual desire disorder. Discovering the etiology and identifying modifiable factors of the sexual function will help define appropriate treatment.
... On average, women in the middle of menopausal transition gained almost 0.5 kg per year.2) This could affect not only high level of cholesterol but also body metabolic system, like basal metabolic rate, so they are recommended to maintain their weight for normal-weight perimenopausal women and to lose their weight to decrease the risk of cardiovascular diseases for overweight or obese perimenopausal women.3,4) ...
Low body weight was one of the risk factors of osteoporosis. Little is known about the correlation between body weight change and bone mineral density (BMD) in Korean women. Therefore, this study was designed to reveal the impact of body weight change on BMD of the lumbar spine in perimenopausal women.
105 healthy perimenopausal women aged between 44 and 50 years old were enrolled from August 2002 to March 2009. BMD was measured by dual energy X-ray absorptiometry. Partial correlation coefficients between body weight change and BMD change were calculated after the adjustments for several variables. BMD changes among groups based on BMI and the percentage change in body weight during 1-year follow-up period were compared.
At both baseline and year 1, BMD of lumbar spine tended to be associated more with body weight. There was a significant association between body weight change and BMD change in lumbar spine during 1-year follow-up period. The weight gain group relatively showed an increase in BMD of lumbar spines than weight loss group. There was no BMD change in BMI less than 23 kg/m(2) group, but in case of BMI more than 23 kg/m(2) group, BMD in weight gain group increased more than the weight maintaining group.
This study demonstrated that body weight change is associated with change in BMD of lumbar spine in perimenopausal women especially if they are overweight.
... This decline in ovarian activity is accompanied by vasomotor reactions, depression and changes in body composition with a decrease in lean mass and an increase in body fat. A high incidence of osteoporotic fractures, cardiovascular diseases and cognitive impairment are other features of estrogen deficiency (Santoro and Chervenak, 2004). ...
Estrogens regulate growth hormone (GH) secretion and modulate the tissue responsiveness to GH. After the menopause, and during ageing, a decline in GH secretion (somatopause) is physiologically observed. This article (i) provides a brief overview of the different regulators of GH secretion, (ii) reviews the mechanisms involved in age-related changes in GH concentrations, with particular emphasis on the interrelationships between menopause and GH, and (iii) discusses the interventions aimed at the restoration of GH and insulin-like growth factor (IGF-1) circulating levels.
A systematic literature search was conducted in the PubMed database using the search terms 'Growth Hormone', 'Somatopause' and 'Menopause'. The search included full English articles covering the period 1972-2008. We selected 234 relevant citations. We also included three chapters from books.
Estrogen deficiency may contribute, through its action on GH, to the complex physical and metabolic alterations of menopause. Several attempts have been made to restore the GH and IGF-1 levels within the young adult range.
There is no definite evidence that elderly subjects really benefit from treatment with GH or GH secretagogues. Strategies aimed at enhancing spontaneous GH secretion such as sleep and exercise are safer and certainly less expensive than GH supplementation regimen.
... In contrast, no effect of recreational PA emerged overall, nor a clear modifying effect of BMI on the PA-MBD association. These women that in the 5-year-period prior to the study ME, experienced the so-called menopause transition, 27 with an unstable hormonal profile, might have diluted the effect(s) on MBD of body weight-related factors more evident in postmenopausal women. ...
A protective effect of physical activity (PA) on breast cancer (BC) risk has been suggested. Few studies have examined the influence of PA on mammographic breast density (MBD), a strong risk factor for BC. In a prospective study in Florence, Italy, we identified 2,000 healthy women with a mammogram taken 5 years after enrollment. Individual mammograms were retrieved (83%) and MBD assessed according to Wolfe's classification. Detailed information on PA at work and during leisure time, reproductive history, lifestyle and anthropometric measurements at enrollment were available for 1,666 women. Information on hormone replacement therapy (HRT) was also obtained at mammogram. Women with high-MBD (P2 + DY Wolfe's patterns) were compared with women with low-MBD (N1 + P1) by multivariate logistic models. Overall, high-MBD was inversely associated with increasing levels of leisure time PA (p for trend = 0.04) and among peri-/postmenopausal women, also with increasing levels of recreational activities (p for trend = 0.02). An interaction between PA and HRT emerged, with a stronger inverse association of highest level of recreational activity with MBD among HRT nonusers (p for interaction = 0.02). A modifying effect by body mass index (BMI) was evident among 1,025 peri-/postmenopausal women who did not use HRT at the time of mammogram, with a stronger inverse association between recreational PA and MBD in the highest BMI tertile (OR = 0.34; 95% CI 0.20-0.57; p for interaction = 0.03). This large study carried out in Mediterranean women suggests that leisure time PA may play a role in modulating MBD, particularly in overweight/obese peri-/postmenopausal women.
... A total of 124 healthy women were studied and divided into groups according to their menstrual bleeding stage 17 . One of the groups consisted of 64 women in the menopausal transition, from 42 to 55 years of age, with an intact uterus. ...
To assess the relationship between the main components of both the metabolic syndrome and insulin resistance and menopausal status in the menopausal transition.
A total of 124 healthy women were divided into four groups according to their menstrual status: the first group consisted of 35 women in menopausal transition with menstrual bleeding (MTM) and with cycles between 35 and 80 days; the second group was composed of 29 women in menopausal transition with 3-6 months of amenorrhea (MTA). The third group consisted of 31 postmenopausal women (PostM) and the fourth group of 29 premenopausal women (PreM) with regular cycles. The metabolic syndrome was evaluated following the ATP III criteria. Evaluation of insulin resistance was made through the HOMA, QUICKI and McAuley indices and the triglycerides/high density lipoprotein (HDL) cholesterol ratio.
The triglycerides/HDL cholesterol ratio increased in MTM, MTA and PostM women in comparison with PreM women. A slight decrease in the QUIKI index (p = 0.06) and a decrease in the McAuley index (p < 0.001) were observed in MTM, MTA and PostM women in comparison to PreM women. The relative frequencies of metabolic syndrome in the four groups were: PreM, 0%; MTM, 20%; MTA, 21%; and PostM, 22% (p = 0.0001). The most frequent markers of the metabolic syndrome were increased waist circumference, low HDL cholesterol levels and hypertension. Linear regression between menopausal status and metabolic syndrome was lost when age was added to the model.
The frequency of metabolic syndrome increased from the time of the menopausal transition to the postmenopause. Abdominal obesity was the most frequent feature observed. Nevertheless, aging erased the effect of the menopause on the metabolic syndrome. In order to prevent cardiovascular disease, the metabolic syndrome must be evaluated from the time of the menopausal transition.
As defined by the World Health Organization (WHO), sexual health is a state of physical, emotional, mental, and social well-being in relation to sexuality. Despite causing a significant distress to women, sexual health issues often go underreported by women. A wide array of risk factors contributes to sexual health problems in women. These include poor general physical health, genitourinary disorders, compromised partner health, and various socio-cultural influences. The pathophysiology underlying these issues is complex, with hormonal changes being a key factor. Other contributing conditions include chronic diseases such as osteoarthritis, pelvic organ prolapse, and vulvovaginal atrophy. Due to the multifactorial nature of sexual health issues, a comprehensive evaluation of the woman’s overall health is necessary. This assessment should include a thorough clinical history, physical examination, and, where appropriate, diagnostic tests to identify underlying health conditions. Treatment strategies should focus not only on symptomatic relief but also on addressing any underlying medical conditions. Patient education is also a vital component of management, empowering women to better understand their condition and participate actively in their care. With appropriate treatment, including medical, psychological, and lifestyle interventions, women can experience significant improvements in their sexual health, leading to a better quality of life.
It is estimated that more than 40 million women will experience menopause during the next 20 years. For most women, approximately one-third of their life will occur in the postmenopausal period (1). Menopause represents a distinct event or stage in the life of a woman that is normal and may have a positive and liberating effect. For a health care provider and for the woman herself, menopause represents an opportunity to assess concerns and implement important disease prevention and health maintenance interventions.
From adolescence, women have a 1.5 to 3 times higher risk than men of suffering from a depressive disorder. This risk increases in the transition period to menopause or perimenopause, when the depressive vulnerability becomes especially intense. Hormonal, psychological and sociocultural factors have been suggested to understand the etiopathogeny of these disorders. Treatment of depression in perimenopause is determined by clinical severity and includes antidepressants, psychotherapy, and sometimes, hormone replacement therapy with estrogens. Perimenopausal depression is an underdiagnosed and poorly treated problem, which generates a high level of suffering and deserves greater attention by clinicians and health systems.
Ageing is related to slowdown/breakdown of the somatotropic axis (i.e. the somatopause) leading to many physiological changes. The somatopause is accompanied by DNA and other macromolecule damage, and is characterized by a progressive decline in vitality and tissue function. We still do not have a definitive understanding of the mechanism(s) of ageing. Several overlapping theories have been proposed such as: 1) The free radical theory, 2) Mitochondrial Ageing, 3) The Glycation Theory, 4) Protein Damage and Maintenance in Ageing, and, 5) DNA Damage and Repair. Furthermore, several models of ageing were introduced such as genetically programmed senescence, telomere shortening, genomic instability, heterochromatin loss, altered epigenetic patterns and long lived cells. There are certain lipid modifications associated with the somatopause, characterized mainly by an increase in total cholesterol and triglyceride levels in both genders.
Introduction
Arterial hypertension (HTA) and osteoporosis are two diseases with many common characteristics. Both have a powerful genetic base of polygenic character. They increase with age, have high prevalence and mainly affect women in the elderly. Both present long-term complications of elevated morbidity-mortality. HTA increases the effect of cardiovascular events and the osteoporosis the risk of fractures.
Material and methods
The group studied were women between 40 and 70 years, with documented menopause, normotension (n=53) and newly diagnosed arterial hypertension (n=51); risk factors for secondary osteoporosis or use of medicaments that may affect the bone mass were ruled out. Bone densitometry and classification were done according to the WHO parameters.
Results
There were no differences in the bone mass between the group of menopausal women with normotension and those with hypertension. However, after comparing the bone mass of the patients with the peak value of bone mass expected in the young population (from 20 to 30 years) of the same gender and race, according to WHO diagnostic parameters of osteoporosis, the group of menopausal women with hypertension had greater prevalence of osteoporosis (p=0.04).
Discussion
Studies conducted in the human species in order to evaluate the relationships between bone mass or osteoporosis and arterial hypertension are scarce. In addition, they use different methodologies and have contradictory results. Among the menopausal women included in the present study, the hypertense group has greater prevalence of osteoporosis than the normotense one.
Not only bone mineral density (BMD) is strongly associated with body weight, but also weight change influences BMD change. The weight change related bone change is more marked in women especially after menopause, in the elderly, in the underweight and in persons who have the history of weight cycling. Because of the health impacts of obesity, weight reduction has been often recommended in practices. Therefore various intervention methods have been tried to reduce the weight change related bone change such as hormone therapy, raloxifene, exercise, and calcium supplementation. This review summarizes the epidemiological evidences of the weight change related bone change and the associated factors.
Blood hormone and tumor marker concentrations are usually determined by immunochemical methods which are based on an unique reaction between antigen and assay capture antibody. Despite the speed and simplicity of assays performance on automatic immunochemistry platforms, the interpretation of final results requires a deep knowledge of method fallibility. General lack of immunoassays standardization, presence of cross-reacting substances in patient's sample, limitation of free hormones measurement due to abnormal analyte binding protein concentrations, assay interferences due to patient's autoantibodies, and heterophilic antibodies, as well as proper interpretation of very low- and very high-sample analyte levels, are the main points discussed in respect to hormones and tumor markers measurement in geriatric population.
The objective of this study was to investigate the association between reproductive events and abdominal obesity (waist circumference, ≥ 88 cm) and general obesity (body mass index, ≥ 30.0 kg/m) in a sample of women between the ages of 40 and 65 years treated at an outpatient clinic in southern Brazil.
This was a cross-sectional study of a sample of 617 women from southern Brazil. Menopause status was classified as premenopausal, women who had regular menstrual cycles; perimenopausal, women who had irregular menstrual cycles whether in periodicity or flow; or postmenopausal, women whose last menstrual period occurred more than 12 months before the time of interview. Poisson regression was used to calculate crude and adjusted prevalence ratios and their respective 95% CIs.
The prevalence rates of abdominal and general obesity were 66.6% (95% CI, 62.8%-70.3%) and 45.5% (95% CI, 41.5%-9.4%), respectively. After adjustment for demographic, socioeconomic, and behavioral variables, early menarche (≤ 11 y) and parity were strong predictors of abdominal and general obesity, presenting a dose-response relationship. Women with a history of three or more pregnancies and menarche at age 11 years or earlier had a 25% higher prevalence of abdominal obesity (95% CI, 1.07-1.46) and a 75% increase in obesity (95% CI, 1.37-2.24) compared with nulliparous or primiparous women with menarche at 14 years or older. Women with a postmenopause status showed an increase of 52% in general obesity, compared with those with a premenopause status.
Characteristics of reproductive life may have a strong influence on body fat buildup in women during the menopausal transition.
Hormone replacement therapy (HRT) remains the gold standard for the management of menopausal symptoms; however, HRT use has declined due to concerns over possible adverse side-effects. Approaches to menopause management are continually being revised and these extend beyond the control of recognized menopausal symptoms to encompass wider aspects of menopausal women's health. Hypertension and associated cardiovascular risk are particularly important unmet needs in postmenopausal women, especially in the Asia-Pacific region which has a rapidly aging population and bears around half of the global burden of cardiovascular disease, two-thirds of which has been attributed to elevated blood pressure. As first point of contact for women with menopausal symptoms, gynecologists play a gatekeeper role in assessing women's health, providing appropriate lifestyle counseling, and, where appropriate, implementing treatment or referral to relevant specialists. This paper, with contributions by gynecologists and cardiologists from Asia Pacific and beyond, summarizes available evidence and provides a treatment algorithm that employs a flexible blood pressure classification strategy to assist physicians in their decision-making for the individualized management of menopausal symptoms in women with low, moderate and high cardiovascular risk, and also for women with diabetes. Individualized HRT according to cardiovascular risk may yield improvements in cardiovascular health, as well as managing menopausal symptoms.
Right ventricular outflow tract tachycardia (RVOT-VT) is a common arrhythmia in young patients without heart disease. The arrhythmia is characterized by repetitive bursts and premature ventricular contractions with a left bundle branch block, inferior-axis QRS morphology, and symptoms of palpitations. Although more frequent in women, sex-specific triggers for symptomatic RVOT-VT have not been identified.
We interviewed 34 women and 13 men referred for ablation of RVOT-VT to determine if predictable but sex-specific exacerbations in symptomatic RVOT-VT exist. After a general query asking if there was predictability to what triggered palpitations, we then specifically queried all patients about symptomatic RVOT-VT initiation with exercise, stress, caffeine, fatigue, and, in women only, periods of recognized hormonal flux. The times identified as states of hormonal flux included premenstrual, gestational, perimenopausal, and coincident with the administration of birth control pills. In response to the completed interview, the most common recorded trigger for RVOT-VT in women was recognized states of hormonal flux with 20 (59%) of 34 women responding positively and 14 (41%) of the 34 indicating that states of hormonal flux were the only recognizable triggers. Men were more likely than women to report that their RVOT-VT was predictably triggered by exercise, stress, or caffeine: 12 (92%) of 13 men versus 14 (41%) of 34 women (P <.01).
Triggers for RVOT-VT initiation are sex specific. Women have RVOT-VT initiation with recognized states of hormonal flux. Men more commonly have RVOT-VT initiated by exercise or stress. These data have important implications related to patient education and counseling in the setting of RVOT-VT and may influence the timing of drug treatment and electrophysiologic evaluation in selected patients.
Studies suggest that African American women may have a greater risk of hot flashes compared to Caucasian women, but the reasons for this are unknown. This study tested the hypothesis that African American women have an increased risk of hot flashes due to racial differences in risk factors for hot flashes, including high body mass index (BMI) and lower estrogen levels.
A population-based study was conducted among women aged 45-54 years. Participants were divided into women who reported ever experiencing hot flashes (n=356) and women who reported never experiencing hot flashes (n=257). Participants provided a blood sample for hormone assays, were weighed and measured, and completed a questionnaire.
Among peri-menopausal women, African American women were more likely than Caucasian women to report any hot flashes (RR=2.08), severe hot flashes (RR=2.19), and hot flashes for more than 5 years (RR=1.61). The risk ratios for the associations between race and the hot flash outcomes were attenuated after controlling for other important hot flash risk factors (i.e. obesity and low estrogen levels).
African American women have an increased risk of hot flashes compared to Caucasian women due to racial differences in a number of risk factors for hot flashes, including advanced age, obesity, current smoking, less than 12 drinks in the past year, and lower estrogen levels.
Although a woman's menstrual history can have significant implications for health outcomes, few studies have examined menstrual cycle variability in non-western, non-clinically based populations. This study presents menstrual cycle characteristics from Bhutia women living in Gangtok, Sikkim, India. The Bhutia are one of two indigenous populations residing in this small, northeastern state of India. A total of 1067 cycles were recorded by 200 Bhutia women over the course of 12 months. Mean cycle length in this population was similar to reported mean cycle lengths for populations in the U.S (30 days vs. 28 days). Menstrual cycles in this sample were highly variable with most women experiencing more than one short or long menstrual cycle. The frequency of irregular menstrual cycles experienced by individuals also varied significantly by season. A body mass index (BMI) above or below the WHO defined normal range was associated with higher rates of irregular cycles. Leutenizing hormone (LH) and follicle stimulating hormone (FSH) levels were also determined from urine samples collected just before mid-cycle, based on median cycle lengths. Although menstrual cycles in this sample were highly variable, median cycle length was still useful in predicting timing of the pre-ovulatory hormone surges of LH and FSH. Frequency of irregular cycles did impact the successful capture of the LH and FSH peak values.
Menopause is a physiologic transition and is assuming an increasing importance as the demographic bulge moves through this phase. The transition takes place over several years. It is characterized by depletion of the ovarian follicles, decreasing inhibin leading to increases in follicle-stimulating hormone and loss of the menstrual cycle, accompanied by decreased estradiol production and typical symptoms. The role of hormone therapy in menopause has shifted from preventive use to a limited role in symptom management, for which it remains the most effective intervention. There is good evidence from observational and randomized trials of an increased risk of breast cancer in women on estrogen plus a progestin, compared with those on estrogen alone. There are insufficient data to be able to determine if there are clinically important differences between various progestins and progesterone with respect to breast cancer risk, nor between different regimens. Even relatively short-term exposure to unopposed estrogen will increase the risk of atypical endometrial hyperplasia or cancer; women who have their uterus should be using a progestational agent. Lifestyle changes at menopause are important and effective for preventive health. Recent evidence suggests that the discordance between epidemiologic studies with respect to cardiovascular outcomes and the Women's Health Initiative randomized controlled trial (WHI RCT) data might be attributable in large part to the older age of women enrolled in the WHI.
Studies of weight loss and changes in bone mineral density (BMD) have primarily been short-term trials in obese subjects.
We examined the effects of a 5-yr intervention designed to prevent menopausal weight gain or promote modest weight loss on BMD in premenopausal women participating in the Women's Healthy Lifestyle Project.
We enrolled 373 premenopausal women (age 44-50 yr) and randomly assigned them to either lifestyle intervention (175 women, low-fat dietary modification, weight loss, and physical activity intervention) or control group (198 women). BMD and body weight were measured at baseline, annual follow-up visits (18, 30, 42, and 54 months), and two postintervention follow-ups (66 and 78 months). BMD was measured by dual x-ray absorptiometry.
Over the 54 months of intervention, women in the intervention group lost 0.4 kg, whereas control women gained 2.6 kg (P = 0.011). The intervention group experienced significantly greater hip bone loss (-0.20%/yr) than the control group (-0.03%/yr). During the postintervention, differences in rates of bone loss disappeared. When considering both menopausal status and use of hormone therapy (HT), the annualized BMD changes were lower in women reporting HT use; nevertheless, among women on HT, those who lost more than 3% body weight experienced greater total hip BMD loss (-0.25%/yr) compared with those who gained weight (-0.02%/yr) (P = 0.025).
Women randomized to a lifestyle intervention aimed at preventing menopausal weight gain or promoting modest weight loss experienced greater rates of hip bone loss than control women.
To assess the effectiveness of professional herbal practice in the treatment of menopausal symptoms. To generate pilot data for future sample size calculations.
A pilot prospective, randomized, waiting list controlled trial was conducted in primary care at one urban UK GP practice. Participants were 45 women aged 46-59, experiencing self-defined menopausal symptoms and no menstrual bleeding for 3 months. Exclusion criteria included use of hormone replacement therapy. Participants were block randomized into a treatment group (n = 15) who received a course of individualized treatment from one of three herbal practitioners, and control group (n = 30) offered treatment after waiting 4 months. Treatment was six consultations over 5 months including discussion of nutrition, lifestyle and individualized herbal prescription. Change in menopausal symptoms was measured in both groups using the validated Greene Climacteric Scale. Measure Yourself Medical Outcome Profile recorded changes in self-defined most troublesome symptoms.
Forty-four participants completed the study. The treatment group demonstrated a statistically and clinically significant reduction in menopausal symptoms compared to the control group. Total scores for menopausal symptoms reduced for both groups. Reduction for the treated group was 9.05 points greater than that for the control group, CI 5.08-13.03, as were changes in vasomotor scores (mean 1.81, CI 1.00-2.62). Libido increased (mean 0.69, CI 0.38-0.99) in the group receiving herbal treatment.
The treatment package from herbal practitioners improved menopausal symptoms, particularly hot flushes and low libido. This offers evidence to support herbal medicine as a treatment choice during the menopause.
Culture, individual health beliefs and distressing symptoms frequently determine women's perceptions of their menopausal transitions. Women's perceptions of mental health problems and the acceptability of different interventions greatly affect if and what a woman is willing to try as a treatment option and whether or not she will accept the possibility that her menopausal symptoms represent a comorbidity with a diagnosis, such as depression or anxiety. These perceptions have a significant impact on women's choices with regard to health practices, as well as on whether or not they will seek out medical care for their distressing symptom(s). Working with a woman's beliefs, sharing decision making, and empowering her through health education are all critical aspects of the treatment of the patient with comorbid perimenopausal symptoms, regardless of their etiology.
Sowers M, Crawford S, Sternfeld B, Morganstein D, Gold E, Greendale G, Evans D, Neer R, Matthews K, Sherman S, Lo A, Weiss G, Kelsey J. SWAN: a multi-center, multi-ethnic, community-based cohort study of women and the menopausal transition. In: Menopause: Biology and Pathobiology, eds. RA Lobo, J Kelsey, R Marcus. San Diego: Academic Press, 2000, pp. 175-188. ISBN 0124537901, 9780124537903.
The changes in serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FHS), estradiol, and progesterone that occur both early and late in reproductive life were characterized and compared with findings in young, normal women and in patients with certain menstrual disorders. A total of 50 complete menstrual cycles in 37 were examined. Five distinct patterns of hormonal regulation were found, three of which are reported here: (a) A long follicular phase and delayed follicular maturation in young women with long, unpredictable intermenstrual intervals from menarche; (b) a short follicular phase with increasing age and in short cycles in perimenopausal women; and (c) true anovulatory vaginal bleeding in long cycles in perimenopausal women. The short cycles before and during the menopausal transition were found to have lower E2 levels and high FSH concentrations throughout, while LH remained in the normal range. During long cycles in perimenopausal women, concentrations of LH and FSH were in the menopausal range. However, follicular maturation was observed months after high levels of gonadotropins were attained. These studies permit the characterization of the menstrual history of the normal woman in terms of the hormonal changes that occur and provide a basis for the definition of several disorders of follicular maturation.
This review of the perimenopause documents its complexity as a hormonal and socio-cultural transition. Early FP FSH levels increase, and short luteal-phase cycles and anovulation become prevalent. However, mean estradiol or estrogen excretion levels are not low. The perimenopause is characterized by higher average (compared with premenopausal women) and erratic estrogen levels. For example, mean early FP estradiol levels (averaging 225 ± 98 pmol/liter) significantly exceeded those found in young fertile women. Estradiol levels preceding flow are also higher in perimenopausal than in premenopausal women. A hypothesis to explain the high estradiol levels, elevated FSH, and inconsistent ovulation postulates that lower inhibin levels (especially in the premenstrual portion of an anovulatory cycle) allow an increase in the early FP FSH level. This high FSH, in turn, stimulates a larger than normal number of ovarian follicles, and each stimulated follicle produces more estradiol. The resulting prolonged high or erratic estradiol levels, coupled with ovulation disturbances including anovulation, probably explain many of the morbidities associated with this phase in a woman's life: menorrhagia, breast tenderness, breast enlargement and fibrocystic breast problems, increased PMS, migraine headaches, increasing fibroid size, and risks for hysterectomy (± ovariectomy). This review proposes a new name for the signs and symptoms of high estrogen levels that some perimenopausal women experience: 'Perimenopausal Endogenous Ovarian Hyperstimulation Syndrome.' This name was chosen because, in hormone levels and pathogenesis, the perimenopausal state is similar to exogenous ovarian hyperstimulation therapy used for infertility treatment. Paradoxically, despite elevated estradiol levels, the perimenopause is associated with a significant rate of spinal BMD loss. Early studies suggest that this loss exceeds that during the early menopausal period. Although this relationship had previously been documented (173), combined data from 10 studies provide increasing statistical evidence that significant, almost 2% per year, spinal bone loss occurs in the year before and after the last flow. These data require a reevaluation of the concept equating low estrogen levels with bone loss. Detailed prospective studies are needed that include measurements of bone changes in parallel with assessments of estradiol, progesterone, ovulation, menstrual cycles, weight (fat and muscle) changes, diet (calcium and Vitamin D), bone resorption and formation markers, and both the hormonal and the experiential aspects of stress. The difficulty in defining the onset of the perimenopause will likely not be resolved until a longitudinal study of the perimenopausal transition is performed that includes women's prospectively recorded experiences in parallel with their hormonal, cycle interval, and ovulation characteristics. Although studies of menstrual cycle intervals, hormone levels, ovulation frequency, and women's symptoms and experiences have each been performed, no study combines all assessments. Such a study would need to extend over a long period of time to encompass a woman's last premenopausal years and to continue until 12 months have elapsed without flow. From data currently published, it is not evident that this lack of information is being rectified by the several important ongoing prospective studies [Melbourne Women's Midlife Health Study, the new National Institutes of Health-funded Study of Women Across the Nation (SWAN) (194)], or the osteoporosis studies in Kuopio, Finland, Hull, United Kingdom, or Malmo, Sweden). The currently conducted Canadian Multicentre Osteoporosis Study (CaMOS)(189,190), which has completed its recruitment of approximately 7,000 women ages 25 to over 80, in nine centres across Canada, has the potential to document the perimenopausal transition in a population-based sample of women. Serum samples have, so far, been obtained in only one center. However, CaMOS is now ready to begin a 3- yr interim data collection for women (and men) who were ages 40-60 at baseline. A 5.0-yr prospective assessment is planned for the entire cohort including about 3000 men. In addition to a detailed questionnaire (demographics, dietary, heredity, diet, reproductive history, quality of life) a Daily Perimenopause Diary has been developed and pilot tested (39). This instrument is similar to both the Menstrual Cycle Diary (195) (including flow characteristics, dysmenorrhea, and vaginal mucus) and to the Daily Menopause Diary (153) in documenting VMS by number and intensity occurring in both the night and day. Using data gathered with the Daily Perimenopause Diary, the CaMOS questionnaire, and bone assessments by DXA and ultrasound that are being documented, an improved understanding of the pathophysiology of perimenopausal bone loss is possible. The perimenopause, in summary, is a unique hormonal transition. It is demonstrably more complex than it was previously understood to be; it is clearly not a time of 'declining ovarian function' (11). Instead, dynamic perimenopausal ovaries produce erratic and high estradiol levels and rarely ovulate normally. These changes in hormonal levels manifest themselves in most aspects of a woman's health and may present as conditions involving almost every system of her body. Because the perimenopause is a time of high social and medical morbidity and is associated with significant costs for the health care system, it is important that research be conducted in impeccably designed prospective observational studies.
Age at menopause and risk of hysterectomy have strong genetic components, but the genes involved remain ill defined. We investigated whether genetic variation at the estrogen receptor (ER) gene contributes to the variability in the onset of menopause in 900 postmenopausal women, aged 55-80 yr, of the Rotterdam Study, a population-based cohort study in The Netherlands. Gynecological information was obtained, and if women reported surgical menopause, validation of type and indication of surgery was accomplished by checking medical records. The ER genotypes (PP, Pp, and pp) were assessed by PCR using the PvuII endonuclease. Compared with women carrying the pp genotype, homozygous PP women had a 1.1-yr (P < 0.02) earlier onset of menopause. Furthermore, an allele dose effect was observed, corresponding to a 0.5-yr (P < 0.02) earlier onset of menopause per copy of the P allele. The risk of surgical menopause was 2.4 (95% confidence interval, 1.5-3.8) times higher for women carrying the PP genotype compared to those in the pp group, with the most prominent effect in women who underwent hysterectomy due to fibroids or menorrhagia. We conclude that genetic variations of the ER gene are related to the onset of natural menopause and the risk of surgical menopause, especially hysterectomy.
A community-based survey was conducted during 1995-1997 of factors related to menopausal and other symptoms in a multi-racial/ethnic sample of 16,065 women aged 40-55 years. Each of seven sites comprising the Study of Women's Health across the Nation (SWAN) surveyed one of four minority populations and a Caucasian population. The largest adjusted prevalence odds ratios for all symptoms, particularly hot flashes or night sweats (odds ratios = 2.06-4.32), were for women who were peri- or postmenopausal. Most symptoms were reported least frequently by Japanese and Chinese (odds ratios = 0.47-0.67 compared with Caucasian) women. African-American women reported vasomotor symptoms and vaginal dryness more (odds ratios = 1.17-1.63) but urine leakage and difficulty sleeping less (odds ratios = 0.64-0.72) than Caucasians. Hispanic women reported urine leakage, vaginal dryness, heart pounding, and forgetfulness more (odds ratios = 1.22-1.85). Hot flashes or night sweats, urine leakage, and stiffness or soreness were associated with a high body mass index (odds ratios = 1.15-2.18 for women with a body mass index > or =27 vs. 19-26.9 kg/m2). Most symptoms were reported most frequently among women who had difficulty paying for basics (odds ratios = 1.15-2.05), who smoked (odds ratios = 1.21-1.78), and who rated themselves less physically active than other women their age (odds ratios = 1.24-2.33). These results suggest that lifestyle, menstrual status, race/ethnicity, and socioeconomic status affect symptoms in this age group.
An unprecedented number of women will experience menopause in the next decade. Although the timing of menopause affects long-term disease risk, little is known about factors that affect this timing. In the present 1995--1997 cross-sectional study, the Study of Women's Health Across the Nation, the relation of demographic and lifestyle factors to age at natural menopause was examined in seven US centers and five racial/ethnic groups. All characteristics were self-reported by women aged 40--55 years (n = 14,620). Cox proportional hazards models were used to estimate the probability of menopause by age. Overall, median age at natural menopause was 51.4 years, after adjustment for smoking, education, marital status, history of heart disease, parity, race/ethnicity, employment, and prior use of oral contraceptives. Current smoking, lower educational attainment, being separated/widowed/divorced, nonemployment, and history of heart disease were all independently associated with earlier natural menopause, while parity, prior use of oral contraceptives, and Japanese race/ethnicity were associated with later age at natural menopause. This sample is one of the largest and most diverse ever studied, and comprehensive statistical methods were used to assess factors associated with age at natural menopause. Thus, this study provides important insights into this determinant of long-term disease risk in women.
To assess the relative influence of menopausal status and hormone use on body mass index (BMI) among a multiethnic sample of mid-life women.
Cross-sectional telephone survey conducted at seven sites where each site targeted an ethnic minority group and Caucasians as part of Study of Women's Health Across the Nation (SWAN).
A total of 7181 Caucasians, 3949 African-Americans, 1660 Hispanics, 562 Chinese Americans, and 803 Japanese Americans between ages of 40 and 55 y residing in or near Boston, Chicago, Detroit, Los Angeles, Newark, NJ, Oakland, CA, and Pittsburgh, PA.
Self-reported BMI based on weight in kg divided by height in m(2) menopausal status, physical inactivity, postmenopausal hormone use, ethnicity, and age in years.
Compared to premenopausal women (covariate adjusted M=27.3), women reporting a surgical menopause (M=28.2) or being in the perimenopausal transition (M=27.7 for early and 27.9 for late perimenopause) had higher BMI. Women reporting a natural menopause (M=27.4) did not have a higher BMI than premenopausal women, after adjusting for chronological age and other covariates. Hormone use was associated with lower BMI (M=26.5 vs 27.3). A comparison of effect sizes showed that menopausal status (F=13.1), followed by chronological age (F=24.0), were the least powerful predictors of BMI, whereas the more powerful predictors were physical activity level (F=1377.1) and ethnicity (F=400.5).
The menopausal transition affects body mass index in mid-life, but the effect is small relative to other influences. Interventions to increase physical activity are highly recommended to prevent increases in adiposity common in mid-life.
It is currently believed that the postmenopausal ovary remains a gonadotropin-driven, androgen-producing gland. However, the adrenal contribution to circulating androgen levels may explain some conflicting results previously reported. In addition, the steroidogenic potential and gonadotropin responsiveness of the postmenopausal ovary have not been recently reassessed. Plasma T, bioavailable T, free T, androstenedione (Adione), and dehydroepiandrosterone sulfate levels were measured in postmenopausal or ovariectomized women with complete adrenal insufficiency, compared with women with intact adrenals. A stimulation human chorionic gonadotropin test (on d 0, 3, and 6) was performed in postmenopausal women with adrenal insufficiency. Dexamethasone was administered for 4 d in postmenopausal women with intact adrenals. Intraovarian T and androstenedione were also measured in homogenates of ovarian tissue from postmenopausal women. Immunocytochemistry was performed on postmenopausal ovaries and premenopausal controls to detect the presence of steroidogenic enzymes (P-450 aromatase, P-450 SCC, 3beta HSD, and P-450 C17) and gonadotropin receptors. Plasma androgen levels were below or close to the limit of the assay in all women with adrenal insufficiency. They were similar in postmenopausal and oophorectomized women with normal adrenals. No hormonal changes were observed after human chorionic gonadotropin injections in women with adrenal insufficiency. In contrast, a dramatic decrease of all steroids was observed after dexamethasone administration in postmenopausal women with intact adrenals. Intraovarian T and androstenedione levels were negligible in postmenopausal ovarian tissue. P-450 aromatase was absent from the 17 ovaries studied, and the enzymes for androgen biosynthesis were either absent (n = 13) or present in very low amounts (n = 4). In all the postmenopausal ovaries, FSH and LH receptors were completely absent. In the absence of adrenal steroids, postmenopausal women have no circulating androgens. This result is consistent with the immunocytochemical studies showing the almost constantly absent steroidogenic enzymes and LH receptors in the postmenopausal ovary. Thus, the climacteric ovary is not a critical source of androgens. The arrest of androgen secretion after menopause may impact significantly on women's health.
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.
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.
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.
Premature menopause, also termed premature ovarian failure (POF), is characterized by cessation of menstruation before the age of 40 years. Little information is available on the general prevalence of POF or on the prevalence by ethnic group. There is also a lack of information on the association of POF with health indicators.
A cross-sectional survey of women aged 40-55 years was conducted at seven sites in the USA to determine eligibility for a community-based, multi-ethnic longitudinal study of the peri-menopause (The Study of Women Across the Nation, SWAN). Interview data were used to (i). determine the prevalence of self-reported POF overall and by ethnic group, and (ii). assess the association of POF with selected self-reported variables related to health. Cases of POF included only women with no discernible cause for POF.
POF was reported by 1.1% (126/11 652) of women. By ethnicity, 1.0% (95% CI, 0.7-1.4) of Caucasian, 1.4% (95% CI, 1.0-2.1) of African American, 1.4% (95% CI, 0.8-2.5) of Hispanic, 0.5% (95% CI, 0.1-1.9) of Chinese and 0.1% (95% CI, 0.02-1.1) of Japanese women experienced POF. The differences in frequency across ethnic groups were statistically significant (P = 0.01). Only Caucasian, African American and Hispanic women were included in further analyses since too few Asian women had POF. In a multivariate model, POF was independently associated with osteoporosis, female hormone use (excluding oral contraceptives), higher body mass index (BMI) and current smoking after adjustment for education level, ability to pay for basics, site and age at interview. In Caucasian women, use of female hormones, osteoporosis, severe disability and smoking were significantly associated with POF. In contrast, POF in African American women was associated with higher BMI and female hormone use, but not osteoporosis.
The prevalence of POF appears to vary by ethnicity. Health factors associated with POF also vary by ethnicity but because of the cross-sectional study design, it is not possible to determine cause and effect relationships. Health risks of POF would benefit from further study.
Since smoking has been shown to affect serum progesterone and estradiol levels in postmenopausal women, we evaluated the levels of these hormones and luteinizing hormone (LH) over an entire menstrual cycle (17 points) in eight healthy nonsmokers and eight healthy smokers. The total length of the cycle and the lengths of the follicular and luteal phases did not differ between the groups. There was no difference in estradiol, progesterone, or LH levels during the periovulatory and luteal phases. Follicular-phase serum progesterone, which had a level 37% higher in smokers, showed a plateau in both groups (28.3 ± 5.7 ng/dl versus 20.7 ± 5.7; P < 0.0001). Follicular-phase serum estradiol showed a rising curve in both groups. The mean value in smokers was slightly higher than that in nonsmokers (107 pg/ml versus 95; P ~ 0.05); during the early part of the follicular phase, prior to the rapid preovulatory increase, the difference was greater (23%) and of higher statistical significance (80 pg/ml versus 65; P < 0.001). The follicular-phase LH levels of smokers were skewed downward from the levels in nonsmokers, presumably by negative feedback from the elevated estradiol and progesterone levels; the difference was significant (P < 0.001). The elevations of serum progesterone and estradiol in smokers probably represent activation of adrenocortical secretion by smoking. The greater and more clear-cut rise of progesterone than of estradiol is probably due to the fact that essentially all of the follicular-phase serum progesterone is secreted by the adrenal, while only part of the follicular-phase serum estradiol comes from the adrenal (via androstenedione and estrone). (Steroids 55:507–511, 1990)
The SWAN is a multiethnic, community-based, longitudinal cohort study of 3302 women at 7 sites who initially were 42 to 52 years of age. Daily patterns of reproductive hormones have been studied in a subgroup of 848 women. A total of 833 menstrual cycles were evaluated. Urinary levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrone conjugate (E1c), and pregnanediol glucuronide (Pdg) were used in algorithms to evaluate menstrual cycles for features of folliculogenesis, ovulation, and corpus luteum function. A significant rise in Pdg was taken as evidence of luteal activity (ELA), which is consistent with ovulation. A 60% decrease in the E1c to Pdg ratio indicated a luteal shift (DLT). Phase-specific lengths of cycles with ELA were estimated using the DLT as day 0, excluding day 0 from both follicular and luteal phase lengths. Hormone levels were summed over the total cycle and over the follicular and luteal phases for cycles with ELA. Participants were 43-53 years of age. Just over one third had smoked, and more than half were either overweight or obese. Just over one fourth of women were premenopausal; the rest were in the early perimenopausal phase.
Approximately 81% of cycles had ELA, and these were the ones used in the following comparisons. Hispanic women had more long cycles exceeding 33 days and fewer short ones less than 22 days. Both longer and shorter cycles were most frequent in women aged 49 and older. Women whose body mass index (BMI) exceeded 25 kg/m2 had longer cycles on average than those with lower values. Early perimenopausal women were likelier than premenopausal women to have long cycles. On multivariate analysis, only age was significantly associated with total cycle length. BMI was the strongest predictor of phase lengths, larger women having longer follicular phases and shorter luteal phases. The differences remained significant on multivariate analysis. The follicular phase was significantly longer on average in early perimenopausal than in premenopausal women. Neither age nor smoking status influenced phase lengths. Hispanic women had longer luteal phases than other ethnic groups, but there were no significant ethnic differences after adjusting for BMI. Apart from E1c, daily hormone levels were highest in women whose BMI was 25 kg/m2 or less. Lower BMI correlated with higher total-cycle E1c values. Chinese and Japanese women had higher Pdg and lower E1c levels, largely because of the influence of BMI. Women over age 49 years had higher total-cycle FSH levels but lower total-cycle PdG values than did younger women. Smoking did not predict Pdg on multivariate analysis. Total-cycle FSH was higher in early perimenopausal than in premenopausal women, partly because of age differences.
Total-cycle hormone levels were related to BMI in this study, and ethnicity seems to play a role independently of body size. It is not clear whether the observed differences are the result of differing rates of progress through the menopausal transition related to body size or ethnicity, or whether the differences will persist with longer follow up.
Differences in age at natural menopause by occupation, education, and place of residence were examined using a cross-sectional population sample of Finnish women aged 45–64 years ( n = 1,713, response rate 86%). The sample was selected at random from the Finnish Population Register in 1989 (final n = 1,505, 75%). Kaplan-Meier estimates showed the median age at natural menopause to be 51 years for all women (95% confidence interval (CI) 50.6–51.4). The median menopausal age of smokers and nulliparous women was 50 years; that of nonsmokers and women whose first full-term pregnancy occurred before the age of 25 years was 52 years. Differences between occupational and educational groups were statistically significant (Mantel-Cox test for occupation, p < 0.02; for education, p < 0.03). In the Cox proportional hazards model, the odds ratio of the occurrence of natural menopause among upper white-collar women was 0.74 (95% CI 0.57–0.96) and among the most educated women (education > 11 years) it was 0.75 (95% CI 0.59–0.96), adjusted to reflect smoking, use of hormones, body mass index, and age at first full-term pregnancy. Sociodemographic variables appear to be associated with age at natural menopause in a representative sample of Finnish women. Am J Epidemiol 1994;139.64–76.
Studies of menstrual cycle length in large populations demonstrated that there is a striking increase in the variability of intermenstrual intervals just before menopause. The changes in serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and progesterone (P) during menstrual cycles in a group of perimenopausal women were compared with the findings in young normal women. In 8 women, 46-56 years old with regular cycles, cycle length was shorter and the mean E2 concentration was lower than in younger women. There was a striking increase in FSH concentration throughout the cycle while LH remained in the normal range. In 2 women, 14 cycles of variable length were studied during 2 years of the menopausal transition. In some instances, hormonal changes associated with follicular maturation and corpus luteum function occurred in the presence of high, menopausal levels of LH and FSH with a diminished secretion of E2 and P. In others vaginal bleeding occurred during a fall in serum E2 with no associated rise in P. Cycles of variable length during the menopausal transition may be due either to irregular maturation of residual follicles with diminished responsiveness to gonadotropin stimulation, or to anovulatory vaginal bleeding that may follow estrogen withdrawal without evidence of corpus luteum function. The observation of elevated FSH concentrations and normal LH levels in perimenopausal women emphasizes the complexity of the hypothalamic-pituitary-ovarian regulatory system and suggests that LH and FSH are modulated independently at the level of the pituitary.
To assess the occurrence of premature ovarian failure, the age-specific incidence rates of natural menopause were determined for a cohort of 1858 women born between 1928 and 1932. These women were identified as Rochester, Minnesota residents in 1950 and were followed for date and type of menopause. A total of nine experienced natural menopause before age 40 years, which represents a 1% risk of natural menopause to age 40. The annual incidence rates of natural menopause per 100,000 person-years were ten for ages 15 to 29 and 76 for ages 30 to 39. In the age group 40 to 44, the incidence of natural menopause increased greatly to 881 per 100,000 person-years at risk.
The excretion of follicle stimulating hormone (FSH), luteinizing hormone (LH), oestrogens and pregnanediol was measured in weekly urine samples collected for 14-87 weeks (median, 43 weeks) from thirty-one perimenopausal women aged 36-55 years (median, 50 years). The results were compared with those found in twenty-two postmenopausal women aged 55.4 +/- 5.4 years (mean +/- SD), and in twenty premenopausal women aged 44.4 +/- 3.4 years with regular, ovulatory, menstrual cycles. Women classed as perimenopausal had a recent history of irregular menstrual cycles following regular cyclicity. The hormone patterns observed in the perimenopausal women varied widely, both between individuals and from time to time in the same individual. They ranged from ovulatory cycles with low premenopausal levels of FSH, to transient episodes indistinguishable from those found in postmenopausal women with high levels of FSH and LH. Between these extremes were patterns rarely seen at other times in reproductive life: namely, (1) in fourteen women on thirty-two occasions lasting 2-9 weeks, postmenopausal levels of FSH and LH occurred in association with high oestrogen levels; (2) in eighteen women on thirty occasions lasting 2-8 weeks, there was an elevation of LH (but not FSH) into the postmenopausal range; (3) in thirteen women on twenty-six occasions lasting 1-2 weeks, there was an elevation of FSH (but not LH) into the postmenopausal range. These patterns were not seen in any of the premenopausal women. Typically, the approach of the menopause was marked by an increased incidence of high postmenopausal levels of FSH and LH. Ovulatory cycles were observed at all stages in the perimenopause, and occurred within 16 weeks of the last menstrual period in seven of the thirteen women who became postmenopausal during the study. It is concluded that the appearance of high levels of FSH and LH is characteristic of the perimenopause and often precedes the sustained loss of sex hormone secretion by the ageing ovary. Postmenopausal biochemical parameters are no guarantee of the postmenopausal state.
Circulating GH and insulin-like growth factor-I (IGF-I) levels in adults generally fall with age. Studies in aging women have rarely controlled for menstrual cycle stage or status or body mass index. We hypothesized that GH and IGF-I levels in reproductive-aged women fall with age despite the stimulatory effects of endogenous estradiol (E2). Eight older reproductive-aged women (aged 42-46 yr) with regular menses, of normal weight, and in good health were compared to a group of eight young control subjects (aged 19-34 yr). Daytime frequent blood sampling was performed in the early follicular phase of the menstrual cycle to characterize pulsatile GH and LH concentrations. Pooled samples were also analyzed for IGF-I, E2, progesterone, and FSH levels. Older reproductive-aged women had lower 12-h integrated daytime GH concentrations (mean +/- SE, 171 +/- 35 vs. 427 +/- 130 micrograms min/L; P = 0.036) than younger controls and a strong trend for lower IGF-I levels (22.7 +/- 2.1 vs. 31.3 +/- 3.5 nmol/L; P = 0.055) than younger controls despite having higher circulating E2 on the day of sampling (368 +/- 51 vs. 167 +/- 20 pmol/L; P = 0.002). We conclude that older reproductive-aged women have lower daytime GH concentrations than younger controls despite having higher E2 levels on the day of sampling and overall normal gonadal hormone parameters.
To determine the changes in cardiovascular risk factors and psychological and physical symptoms that occur during the perimenopause.
Cohort study of 541 healthy middle-aged premenopausal women followed up through the menopause.
General community.
After a baseline evaluation taken at study entry, 152 women ceased menstruating for 3 months (not due to surgery) and were not using hormone replacement therapy, and were reevaluated in a similar protocol (perimenopausal examination); 105 of the 152 were evaluated a third time when they had ceased menstruating for 12 months and were not using hormone replacement therapy (postmenopausal examination). One hundred nine premenopausal women who were repeatedly tested constituted a comparison group.
Levels of lipids and lipoproteins, triglycerides, fasting glucose and insulin, blood pressure, weight, height, and standardized measures of psychological symptoms.
Women who became perimenopausal showed increased levels of cardiovascular risk factors, which were similar in magnitude to those experienced by the comparison group of premenopausal women. Perimenopausal women reported a greater number of symptoms, especially hot flashes, cold sweats, joint pain, aches in the skull and/or neck, and being forgetful; reports of hot flashes at the perimenopausal examination were associated with low concentrations of serum estrogens. Menopausal status was not associated with depressive symptoms. Perimenopausal women who became postmenopausal showed a decline in the level of high-density lipoprotein-2-cholesterol (means, 0.53 to 0.43 mmol/L [20.6 to 16.7 mg/dL]) and a gradual increase in the level of low-density lipoprotein cholesterol (means, 3.14 to 3.33 mmol/L [121.3 to 128.8 mg/dL]), whereas symptom reporting declined.
During mid-life, women experience adverse changes in cardiovascular risk factors and a temporary increase in total number of reported symptoms, with no change in depression. Preventive efforts to reduce the menopause-induced increase in cardiovascular risk factors should begin early in the menopausal transition.
The authors present a method for defining the inception of perimenopause that is based on self-reported data. The study sample (n = 1,550) was obtained from a 5-year longitudinal study of 2,569 Massachusetts women aged 45-55 years that began in 1981. The definition was derived from the ability of responses to questions concerning timing of the last menstrual period, menstrual regularity, and presence of menopausal symptoms (hot flashes/sweats) to predict menopause 3 years later. The two items that best defined the inception of perimenopause were 3-11 months of amenorrhea and increased menstrual irregularity for those without amenorrhea. This definition can easily be used in large epidemiologic investigations.
To assess the effect of nonsurgical management of leiomyomas, abnormal uterine bleeding, and chronic pelvic pain on symptoms and quality of life.
We performed a prospective cohort study of women receiving nonsurgical management (n = 380) or hysterectomy (n = 311) for leiomyomas, abnormal uterine bleeding, or chronic pelvic pain. Patients recruited from the practices of 63 physicians throughout Maine were interviewed at the outset of treatment and 3, 6, and 12 months later. The principal outcome measures were frequency and severity of physical and psychological symptoms, and quality of life as measured by validated indices of mental and general health and physical activity.
Medical therapy for abnormal bleeding and chronic pelvic pain produced significant improvements in symptoms and quality of life. However, almost one-quarter of patients initially treated nonsurgically subsequently underwent hysterectomy; of patients continuing nonsurgical therapy, 25% with abnormal bleeding and 50% with chronic pelvic pain reported substantial levels of symptoms after 1 year. There were no significant changes in symptoms and quality of life in patients treated nonsurgically for leiomyomas. New problems including tiredness, hot flashes, weight gain, and depression developed in 10% or less of women who did not report these symptoms preoperatively. A logistic regression analysis controlling for age, reproductive history, and severity of symptoms showed that hysterectomy was the factor most highly correlated with a positive outcome at 1 year for all three conditions.
Many women with leiomyomas, abnormal bleeding, and chronic pelvic pain report improved symptoms over time with nonsurgical management. Hysterectomy remains an important alternative when conservative treatment fails.
To investigate black-white differences in factors related to hysterectomy.
Discharge summary data were analyzed for 53,159 hysterectomies that occurred in Maryland from 1986-1991.
The average annual age-adjusted hysterectomy rate was higher for black women (49.5 per 10,000) than for white women (41.2 per 10,000). For 65.4% of the hysterectomies in black women, the principal diagnosis was uterine fibroids, compared to 28.5% for white women. Logistic regression was used to measure the effect of race on complications, length of stay, and mortality after adjustment for a variety of factors including age, comorbidities, diagnosis, route (abdominal, vaginal, or subtotal), hospital characteristics, and source of payment. In comparison to white women, black women having hysterectomy were found to have an increased risk of one or more complications of surgical or medical care (odds ratio 1.4, 95% confidence interval [CI] 1.3-1.5), a length of stay of more than 10 days (odds ratio 2.7, 95% CI 2.5-3.1), and in-hospital mortality (odds ratio 3.1, 95% CI 2.0-4.8).
In a study of more than 53,000 hysterectomies, black women were more than twice as likely to have a diagnosis of uterine fibroids as white women, were more likely to have complications, had a longer hospitalization, and had more than three times the in-hospital mortality rate.
Medical therapy for women in the perimenopausal period is controversial, in part due to varying degrees of ovarian hormone secretion characteristic of this time of life. To extend our understanding of the reproductive endocrine milieu of perimenopausal women, we studied 6 cycling women, aged 47 yr and older, for 6 months with daily collections of first morning voided urine. Five additional older reproductive aged (43-47 yr old) women were studied with daily urine and serum sampling for a single menstrual cycle; their urinary hormone data were combined with the former group for menstrual cycle comparisons. Urine was assayed for LH, FSH, estrone conjugates, and pregnanediol glucuronide and normalized for creatinine (Cr). Eleven midreproductive aged (19-38 yr old) normally cycling women, 5 women with well defined premature ovarian failure, and 5 women aged 54 yr and older who were at least 1 yr postmenopausal were used for comparison. Perimenopausal women had shorter follicular phases (11 +/- 2 days vs. 14 +/- 1 days; P = 0.031) and, hence, shorter menstrual cycles than midreproductive aged controls. FSH excretion in perimenopausal women was greater than that in younger women (range of means, 4-32 vs 3-7 IU/g Cr; P = 0.0005). LH secretion was overall greater than that in younger normal subjects (range of means, 1.4-6.8 vs. 1.1-4.2 IU/g Cr; P < 0.026). Overall mean estrone conjugate excretion was greater in the perimenopausal women compared to that in the younger women [76.9 ng/mg Cr (range, 13.1-135) vs. 40.7 ng/mg Cr (range, 22.8-60.3); P = 0.023] and was similarly elevated in both follicular and luteal phases. Luteal phase pregnanediol excretion was diminished in the perimenopausal women compared to that in younger normal subjects (range for integrated pregnanediol, 1.0-8.4 vs. 1.6-12.7 microg/mg Cr/luteal phase; P = 0.015). Compared to postmenopausal women, perimenopausal women had more overall estrone excretion (2.5-6.2 ng/mg Cr in postmenopausal women; P = 0.02) and lower mean FSH (range of means for postmenopause, 24-85 IU/g Cr; P = 0.017) and LH (range for postmenopause, 4.3-14.8 IU/g Cr; P = 0.041). Compared to women with premature menopause, perimenopausal women again had lower FSH (range of means for premature menopause, 36-82 IU/g Cr; P = 0.0022), lower LH (range of means for premature menopause, 5.5-23.8 IU/g Cr; P = 0.0092), borderline higher mean estrone conjugates (range of means for premature menopause, 4-44 ng/mg Cr; P = 0.064), and far longer periods of ovarian activity (one to two cycles in prematurely menopausal women vs. three to six cycles in perimenopausal women). We conclude that altered ovarian function in the perimenopause can be observed as early as age 43 yr and include hyperestrogenism, hypergonadotropism, and decreased luteal phase progesterone excretion. These hormonal alterations may well be responsible for the increased gynecological morbidity that characterizes this period of life.
This study sought to compare circulating and follicular fluid (FF) concentrations of dimeric inhibin A and B utilizing specific two-site ELISAs for these hormones in normal older and younger ovulatory women. METHODS. Normally ovulating women age 40-45 (n = 10) and 20-25 (n = 13) were studied throughout the follicular phase with daily blood sampling, transvaginal ultrasound examinations, and dominant follicle aspiration. When the dominant follicle reached a mean diameter of 16 mm or serum estradiol (E2) was > or = 550 pmol/L, 10,000 IU of hCG was administered intramuscularly followed 32 hours later by transvaginal follicle aspiration. Serum and FF samples were analyzed for E2, FSH, and inhibin A and B. Daily hormone levels were compared by ANOVA, and mean results were compared using t-tests. RESULTS:Older women developed a dominant follicle sooner, meeting criteria for hCG cycle day 10.6 +/- 0.4 vs. 14.5 +/- 1.0 p < 0.001. As expected, the older group had higher maximal serum FSH concentrations compared to the younger women (11.4 +/- 0.5 vs. 8.0 +/- 0.4 IU/L, p < 0.001). We compared hormone concentrations from days-1 to 3 (where day 0 = day of maximal FSH concentration). E2 concentration was higher in the older women (p = 0.002), and there was no significant difference in inhibin A secretion (p = 0.61). In contrast, mean inhibin B concentration was significantly lower in the older women (p = 0.04). On the day of aspiration of the dominant follicle, serum inhibin B was decreased in the older subjects (42.6 +/- 6.5 vs. 153.1 +/- 53 pg/ml, p = 0.02), whereas older subjects had higher levels of inhibin A (106 +/- 16 vs. 60.4 +/- 9.4 pg/ml, p = 0.04) and similar E2 levels (665 +/- 35.2 vs. 687 +/- 92 pmol/L, p = 0.83). There were no differences in FF concentrations of inhibin B (164 +/- 31 vs. 174 +/- 37 ng/ml, p = 0.85), inhibin A (317.7 +/- 38 vs. 248 +/- 57 ng/ml, p = 0.16), or E2 (2074 +/- 294 vs. 2474 +/- 338 nmol/L, p = 0.82) in the older and younger women. CONCLUSION. Follicular phase inhibin B secretion is decreased in older ovulatory women who demonstrate a monotropic FSH rise, whereas inhibin A secretion is similar to that in younger women. The dominant follicle in these older women appears to be normal in terms of FF E2 and inhibin content. We speculate that decreased inhibin B secretion most likely reflects a diminished follicular pool in older women and may be an important regulator of the monotropic FSH rise.
This review emphasizes results from population based studies in order to provide a reliable knowledge base and define major knowledge gaps for future research.
The review systematically addresses the following aspects of menopause research: definition of menopause and menopause transitions; age at natural menopause and at inception of perimenopause; factors affecting timing and length of menopause transitions; concurrent hormone, menstrual and vascular changes. Under each substantive heading, available reports of original research are reviewed, assessed for reliability and summarized with respect to their contribution to the knowledge base.
From this review, the following reliable information can be summarized: median age at natural menopause in Caucasian women occurs between 50 and 51-55 years of age, is not affected by timing of surgical menopause and is affected by cigarette smoking, with current smokers having an earlier menopause by 1.5-2.0 years. No other factors appear to have an independent effect on age at menopause. There is no evidence of any secular trend in age at menopause. Evidence is accumulating that most physiological change associated with menopause either occurs or begins before the final menstrual period.
We lack reliable information on the following: estimates of age at menopause from non-industrialized countries and diverse ethnic groups; information on perimenopause; differing perceptions of menopause, cross culturally; multi-disciplinary prospective data that can link various processes into coherent patterns.
We hypothesized that the increased FSH noted in older reproductive-aged women is due to both decreased inhibin and increased activin A secretion.
Comparative clinical study.
An academic research center.
Five cycling women, aged 43 to 47, were compared to five midreproductive women, aged 19 to 38.
Specimens taken every 2 to 3 days were assayed for inhibin A and B and activin A.
Integrated concentrations of inhibin A, inhibin B, and activin A in the follicular phase, luteal phase, and whole cycle.
Follicular inhibin B was reduced in older versus younger women (504 +/-82 versus 748+/-72 total pg). Luteal inhibin A was reduced in older versus younger women (668 +/-72 versus 1152+/-216 total pg). Activin A was elevated throughout the cycle of older versus younger women, without within-cycle fluctuations (21+/-2 versus 11+/-1 total ng).
Lack of restraint by inhibin A and inhibin B contributes to the FSH rise associated with reproductive aging. This loss of restraint occurs in a tandem fashion, with inhibin B reduction before ovulation and inhibin A reduction after ovulation. Activin A may also play an endocrine role in maintaining elevated FSH in older reproductive-aged women.
To identify symptoms that change in prevalence and severity during midlife and evaluate their relationships to menopausal status, hormonal levels, and other factors.
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).
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).
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.
The objectives of this study were to measure patient satisfaction with the results of hysterectomy and to determine factors associated with dissatisfaction. Study Design: A total of 1299 women who underwent hysterectomy at 28 hospitals in Maryland were interviewed before and at 3, 6, 12, 18, and 24 months after the operation.
At 12 and 24 months after the hysterectomy 95.8% and 96.0%, respectively, reported that the hysterectomy had completely or mostly resolved the problems or symptoms they had before surgery; 93.3% and 93.7%, respectively, reported that the results were better than or about what they expected; 85.3% and 81. 6%, respectively, reported that their health was better than before the hysterectomy; and 87.9% and 93.1%, respectively, reported being totally recovered. The factor most strongly and consistently associated with patient reports of negative outcomes was readmission because of a postdischarge complication.
Postdischarge complication necessitating readmission plays an important role in patient dissatisfaction with the results of hysterectomy.
This study examined the association between psychologic distress and natural menopause in a community sample of African American, White, Chinese, Hispanic, and Japanese women participating in a national women's health study.
A cohort of 16,065 women aged 40 to 55 years provided information on menstrual regularity in the previous year, psychosocial factors, health, and somatic-psychologic symptoms. Psychologic distress was defined as feeling tense, depressed, and irritable in the previous 2 weeks.
Rates of psychologic distress were highest in early perimenopause (28.9%) and lowest in premenopause (20.9%) and postmenopause (22%). In comparison with premenopausal women, early perimenopausal women were at a greater risk of distress, with and without adjustment for vasomotor and sleep symptoms and covariates. Odds of distress were significantly higher for Whites than for the other racial/ethnic groups.
Psychologic distress is associated with irregular menses in midlife. It is important to determine whether distress is linked to alterations in hormone levels and to what extent a mood-hormone relationship may be influenced by socioeconomic and cultural factors.
To estimate the prevalence of perceived poor sleep in women aged 35-49 years and to correlate sleep quality with levels of gonadal steroids and predictors of poor sleep.
A cohort of 218 black and 218 white women aged 35-47 years at enrollment (aged 37-49 at final follow-up) with regular menstrual cycles was identified through random digit dialing for a longitudinal study of ovarian aging correlates. Data obtained at four assessment periods, including enrollment, over a 2-year interval were collected between days 1 and 6 (mean = 3.9) of the menstrual cycle. The primary outcome measure was subjects' rating of sleep quality at each assessment period. Associations of sleep quality with hormone levels (estradiol, follicle-stimulating hormone, luteinizing hormone, testosterone, and dehydroepiandrosterone sulfate) and other clinical, behavioral, and demographic variables were examined in bivariable and multivariable analyses.
Approximately 17% of subjects reported poor sleep at each assessment period. Significant independent associations with poor sleep included greater incidence of hot flashes (odds ratio [OR] 1.52; 95% confidence interval [CI] 1.08, 2.12, P =.02), higher anxiety levels (OR 1.03; 95% CI 1.00, 1.06, P =.04), higher depression levels (OR 1.05; 95% CI 1.02, 1.07, P <.001), greater caffeine consumption (OR 1.25; 95% CI 1.04, 1.49, P =.02), and lower estradiol levels in women aged 45-49 (OR 0.53; 95% CI 0.34, 0.84, P =.006), after adjustment for current use of sleep medications.
Both hormonal and behavioral factors were associated with sleep quality. Estradiol levels are an important factor in poor sleep reported by women in the 45-49 age group. Further evaluation of estrogen treatment for poor sleep of women 45 years and older is warranted.
This study examined risk factors for functional limitations in a community-based sample of 16,065 women from 5 ethnic groups, aged 40-55 years, enrolled in the Study of Women's Health Across the Nation. Almost 20% of this sample reported physical-functioning limitations. Functional limitations were associated with numerous disease conditions, including high blood pressure, diabetes, heart attack or angina, arthritis, osteoporosis, and cancer, and with several behavioral and environmental risk factors, including body mass index, difficulty paying for basics, and high levels of perceived stress. Consistent with findings in older women, this study shows that in addition to health conditions, potentially modifiable risk factors including high body mass index, difficulty paying for basics, and high levels of stress are associated with physical-functioning limitations of women at midlife.
A select group of investigators attended a structured workshop, the Stages of Reproductive Aging Workshop (STRAW), at Park City, Utah, USA, in July 2001, which addressed the need in women for a staging system as well as the confusing nomenclature for the reproductive years.
To determine whether postmenopausal status is associated with elevated plasma inflammation markers compared to premenopausal status, and how this explains differences in fat distribution and insulin-stimulated glucose disposal.
Cross-sectional.
Clinical research center.
Forty-five premenopausal women and 44 postmenopausal women.
None.
C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) were measured by ELISA. Intraabdominal, subcutaneous abdominal, and total fat were measured by computed tomographic scan and dual-photon x-ray absorptiometry. Insulin-stimulated glucose disposal was measured by euglycemic clamp.
The TNF-alpha was higher in postmenopausal compared to premenopausal women (4.81 +/- 1.99 vs. 3.54 +/- 0.85 pg/mL). Interleukin-6 and CRP did not differ by menopausal status. In both premenopausal and postmenopausal women, CRP was related positively to total fat. The CRP was related to intraabdominal fat only in postmenopausal women and was negatively related to insulin-stimulated glucose disposal in both premenopausal and postmenopausal women.
Postmenopausal status is characterized by higher TNF-alpha. The CRP may be associated with increased cardiovascular risk in postmenopausal women by its association with higher intraabdominal fat. Higher CRP is associated with lower insulin-stimulated glucose disposal in both premenopausal and postmenopausal women.
To characterize premenopausal menstrual regularity and the patterns of divergence from regularity associated with the approach of the final menstrual period.
Two samples of individual cycle length sequences contributed by participants in a population-based longitudinal study of the menopausal transition were examined. The first sample, of "early" sequences, is used to characterize menstrual regularity. The second shows how cycle length patterns change as the final menstrual period (FMP) is approached. Regression slopes are used to measure trend in cycle length, and changes in cycle length variability are registered by a simply calculated measure, the "running range."
Sequences in the early cycles sample rarely varied outside the 21-35 day range and did not show a rising or falling trend. In contrast, pre-FMP sequences generally became increasingly variable in length, while rising above 35 days in mean during the last 10 cycles. The variability measure remained below 40 days throughout the early sequences, but characteristically rose above 42 days during sequences including the last 20 pre-FMP cycles. In early sequences, but not in pre-FMP sequences, long and short cycles tended to alternate.
Increased variability is the dominant feature of cycle length pattern for most women as their final menstrual period approaches. Underlying this is a steady trend toward mean cycle lengths above 35 days. An indicator of the approach of menopause is a rise in running range of cycle lengths to 42 days.
To determine which aspects of menstrual change best predict time to postmenopause.
A total of 250 Australian-born women aged 45-55 years were divided into five menstrual status categories: Group I reported no change in menstrual flow or frequency; Group II reported change in flow; Group III reported change in frequency; Group IV reported change in both frequency and flow; and Group V reported between 3 and 11 months of amenorrhea. Menstrual status groups were compared on baseline data for age, hormone levels, hot flushes and self-rated menopausal status. The proportion of women moving to postmenopause in subsequent years was compared using 4 years of follow-up data.
Women in Group V were older, had lower estradiol and inhibin levels, higher follicle stimulating hormone levels, and were more likely to report hot flushes, and to self-rate themselves as having started the menopausal transition, compared with the women who had menstruated in the last 3 months (Groups I-IV). Groups I and II were similar in age and hormonal status, as were Groups III and IV. The proportion of women who had moved to postmenopausal status in the 4 years after baseline were 12%, 14%, 58%, 53% and 94% for Groups I-V, respectively.
Amenorrhea is the best predictor of future menopause followed by changes in menstrual frequency. Change in flow only was not predictive of future menopause. A two-stage classification scheme is suggested for defining the perimenopause. 'Early perimenopause' is defined as the self-reporting of changes in menstrual frequency over the last year, and 'late perimenopause' is defined as the self-report of 3-11 months of amenorrhea.
To estimate the incidence and regression rates of uterine leiomyomata and polyps in a cohort of asymptomatic, premenopausal women.
Saline infusion sonography was performed twice, 2.5 years apart, in a cohort of 64 initially asymptomatic women. Subjects completed a questionnaire that assessed the development of abnormal uterine bleeding.
The mean age of women (at second ultrasound) was 44 years. In four of seven women with polyps at the original ultrasound, their polyps regressed. Polyps that regressed tended to be smaller than polyps that persisted. Ten women had endometrial polyps at the second ultrasound for a point prevalence of 16% and a cumulative incidence rate of 12% per 2.5 years. A higher percentage of women with uterine polyps had complaints of abnormal uterine bleeding than women with no uterine abnormalities (70% versus 33%, P =.04). Six leiomyomata in four women were no longer detected in the second ultrasound. Leiomyomata that regressed were in older premenopausal women and were smaller than leiomyomata that persisted. The point prevalence and incidence rates of leiomyomata were 27% and 13% per 2.5 years, respectively. Leiomyomata grew an average of 1.2 cm per 2.5 years, but great variation in growth rates were noted.
Small uterine polyps frequently regressed spontaneously, whereas larger polyps were more likely to persist and were associated with the development of abnormal bleeding. Smaller leiomyomata in older premenopausal women also regressed whereas larger leiomyomata tended to grow while often remaining asymptomatic.
To compare age-adjusted and ethnic differences in prevalences of sleep difficulty at various stages of the menopausal transition and to determine the relative contribution of other factors, including vasomotor symptoms, sociodemographics, and psychological and physical health factors, to self-reported sleep difficulty in middle-aged women.
A community-based survey of women's health and menopausal symptoms was conducted between November 1995 and October 1997 at each of the seven US sites participating in the Study of Women's Health Across the Nation. A multiethnic sample of 12,603 Caucasian, African American, Chinese, Japanese, and Hispanic women aged 40 to 55 years was categorized into six groups: premenopausal, early perimenopausal, late perimenopausal, naturally postmenopausal, surgically postmenopausal, and postmenopausal receiving hormone replacement therapy. The women were asked whether they had experienced difficulty sleeping in the past 2 weeks.
Difficulty sleeping was reported by 38%. Age-adjusted rates were highest in the late perimenopausal (45.4%) and surgically postmenopausal (47.6%) groups. Among ethnic groups, rates ranged from 28% in Japanese women to 40% in Caucasian women. In the multivariate analysis, menopausal status was significantly associated with difficulty sleeping. Ethnicity, vasomotor and psychological symptoms, self-perceived health and health behaviors, arthritis, and education also were significantly associated with difficulty sleeping.
These results suggest that stage of the menopausal transition, independent of other potential explanatory factors, is associated with self-reported sleep difficulty. Older age per se was not significantly associated with difficulty sleeping.
We measured serum reproductive hormone concentrations in a community-based, multiethnic population of premenopausal and early perimenopausal women to determine whether there are ethnic differences in hormones that can be explained by host factors. We studied 2930 participants in the Study of Women's Health Across the Nation who were aged 42-52 yr and self-identified as African-American (27.6%), Caucasian (47.1%), Chinese (7.4%), Hispanic (8.8%), or Japanese (9.0%) at 7 clinical sites. Outcome measures from this baseline assessment of a longitudinal study were serum estradiol (E2), FSH, testosterone (T), dehydroepiandrosterone sulfate, and SHBG concentrations and calculated estimates of free steroid availability, free testosterone index, and free E2 index from serum collected primarily in the early follicular phase of a spontaneous menstrual cycle. The primary explanatory variables were race/ethnicity, menopausal status, age, body mass index, day of the cycle, smoking, alcohol use, and physical activity. Chinese women had lower unadjusted E2 and SHBG levels, and Hispanic women had lower unadjusted T levels than other ethnic groups. Unadjusted serum FSH levels did not differ by race/ethnicity. E2 levels adjusted for host characteristics, particularly body size, did not differ by race/ethnicity. Adjusted FSH levels were higher, and adjusted T levels were lower in African-American and Hispanic women. Serum E2 and FSH concentrations were highly variable. Serum FSH levels, but no other hormone concentrations, were positively correlated with menopausal status. Serum dehydroepiandrosterone sulfate levels were negatively correlated with age, but not menopausal status. All hormone concentrations were significantly correlated with body mass index. We conclude that serum sex steroid, FSH, and SHBG levels vary by ethnicity, but are highly confounded by ethnic disparities in body size.
Hysterectomy among women of reproductive age, United States, update for
- Irwin Kl Peterson Hb
- Hughes
- Jm
- Gill
- Sw
Irwin KL, Peterson HB, Hughes JM, Gill SW. Hysterectomy among women of reproductive age, United States, update for 1981–1982.
Characterization of reproductive hormonal dynamics in the perimenopause
- Santoro
Influence of the perimenopause on cardiovascular risk factors and symptoms of middle-aged healthy women
- Matthews