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Endocrinol Metab Clin N Am 33 (2004) 675689

Acute consequences of the menopausal transition: the rise of common menopausal symptoms
Clarisa R. Gracia, MDa,b,*, Ellen W. Freeman, PhDc,d
a

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA b Penn Fertility Care, 3701 Market Street, Suite 800, Philadelphia, PA 19104, USA c Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA d Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

More than 80% of women experience psychologic or physical symptoms in the late reproductive years, with varying degrees of severity and disruption in their lives [1]. Some of the acute consequences of the menopausal transition involve an onset of vasomotor symptoms, mood changes, sleep diculties, and changes in sexual functioning. Both patients and clinicians have misconceptions about what changes are considered normal or abnormal during this period, however. Information on the normal process of reproductive aging and its acute consequences is limited by various factors. Cross-sectional study designs, small sample sizes, suboptimal assessment, and lack of adjustment for confounding factors plague the literature. Recently, large-scale longitudinal studies have been conducted to better characterize and explore changes during this period. This is an important area of inquiry for clinicians, because they are frequently confronted with complaints from symptomatic women in the menopausal transition. This article reviews the current evidence regarding the acute symptoms of the menopausal transition. Specically, the article addresses vasomotor symptoms, mood changes, sleep problems, and changes in sexual functioning.

* Corresponding author. Penn Fertility Care, 3701 Market Street, Suite 800, Philadelphia, PA 19104. E-mail address: cgracia@obgyn.upenn.edu (C.R. Gracia). 0889-8529/04/$ - see front matter 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.ecl.2004.07.003

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Vasomotor symptoms Characteristic symptoms The sudden sensation of extreme heat in the upper body, particularly the face, neck, and chest is referred to as a hot ash. Perspiration, ushing, chills, clamminess, anxiety, and occasionally palpitations can occur [2]. These episodes vary in frequency and duration. Studies show that 87% of women who report hot ashes experience these symptoms on a daily basis. Furthermore, approximately one third of these women experience more than 10 hot ashes per day. On average, the episodes last between 1 and 5 minutes [3]. Sleep disruption has been demonstrated with physiologic measures of hot ashes [4]. Prevalence Vasomotor symptoms are the most common symptom of the menopause and can be troublesome for women. In the United States, the prevalence among naturally menopausal women has been reported to be between 50% and 82% [5,6]. The occurrence of vasomotor symptoms increases from premenopause to peri- and postmenopause [7]. According to Kronenberg [3], the median age of onset is 51 years and the median length of time symptoms last is 4 years. More recent studies show that these symptoms last 1 to 2 years after menopause but may persist in up to 10% of women for 15 years after menopause [8]. Recent studies suggest that hot ashes may occur even earlier than expected, before the menopausal transition. As part of the Penn Ovarian Aging Study, a cross-sectional analysis of enrollment data from 308 latereproductive-aged women was performed to identify factors associated with symptom reporting. Overall, 30% of the subjects reported hot ashes, even though their mean age was 41 years and all were premenopausal (no menstrual irregularities). These ndings suggest that menopausal symptoms may occur earlier in the late reproductive years than has been commonly recognized and may not be entirely caused by menopausal declines in estradiol levels [9]. Pathophysiology The pathophysiology of the hot ash is not clearly understood. It is hypothesized that the thermoregulatory mechanisms change during the transition so that the thermoregulatory zone is narrowed and becomes more sensitive to subtle changes in core body temperature. Small increases in temperature lead to what is known as a hot ash (vasodilatation, sweating, and decreased skin resistance). Freedman [2] conducted numerous physiologic studies exploring hot ashes. The author conrmed that uctuations in core body temperature are more pronounced in postmenopausal women

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compared with premenopausal women. The author was unable to detect dierences in core body temperature uctuations between women with and without hot ashes, however [10]. Although there is little doubt that estrogen is important in the pathophysiology of hot ashes, changes in estrogen alone do not account for vasomotor symptoms. Levels of estrogens have not been found to correlate with hot ashes. Instead, the mechanism of action seems to be centrally mediated. Although there is evidence that hot ashes are temporally related to luteinizing hormone (LH) pulses, other evidence suggests that LH is not the direct cause. More likely, noradrenergic stimulation in conjunction with estrogen triggers thermoregulatory changes resulting in hot ashes [2]. Clearly, more work must be done to elucidate the underlying pathophysiology of vasomotor symptoms during this period so that specic therapies can be developed. Risk factors Epidemiologic studies have been performed to identify risk factors for vasomotor symptoms. Racial and ethnic dierences were shown to be important in vasomotor symptom reporting in the Study of Womens Health Across the Nation (SWAN). Results of this cross-sectional survey of 14,906 multiethnic women aged 40 to 55 years in the United States indicated that African American women reported signicantly more vasomotor symptoms, white women reported more psychosomatic symptoms, and Asian women reported the fewest symptoms compared with other groups [11]. In addition, the Penn Ovarian Aging Study (POAS) showed that African American women reported more physiologic symptoms (hot ashes, dizziness, clumsiness, urine leaks, and vaginal dryness) compared with white women even when adjusting for age, body mass index (BMI), and demographic factors [9]. Such racial and cross-cultural variability in the prevalence of self-reported hot ashes is substantiated by other literature as well [5,8,12,13]. It is possible that menopausal symptoms are not a universal phenomenon but dier by race and ethnicity. Authors have speculated that physiologic dierences or diets high in soy products may account for variable symptoms. Ethnic variations also may be caused by diering crosscultural perceptions and reporting of vasomotor symptoms. Several studies have reported that hot ashes are more common in women with greater body weight. Data from the POAS also show this relationship, which challenges the prevailing view that hot ashes are more common in thin women and raises important questions about the role of BMI in hormone dynamics of the late reproductive years [9]. Other factors related to vasomotor symptoms include low socioeconomic status, smoking, and physical inactivity [7]. Vasomotor symptoms are important and troublesome for many women around the menopausal transition. The existing literature shows that

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symptom reporting depends not only on racial and ethnic dierences but also on obesity, physical inactivity, smoking, and socioeconomic variables. Much work remains to be done to better understand the mechanisms underlying these symptoms to identify modiable risk factors and adequate treatments.

Mood In general, studies have had inconsistent ndings with respect to menopausal status and mood. Many community-based studies have found no association between depressive symptoms, anxiety or irritability, and menopausal status. Others have demonstrated that mood is transiently aected during the menopausal transition period. Some of these inconsistent results may actually reect biases across studies. There are various challenges inherent in studying the relationship between menopause and mood. What aspect of mood disruption, its severity, and how these are assessed are critical issues. Also, the assessment of menopausal status has been controversial and has diered across studies. Perhaps more challenging is the fact that both mood and menopausal status are dynamic. Studying acute changes of the menopausal transition requires longitudinal studies using models that account for change over time within the woman and comparisons of patterns among groups of women [14]. In addition, the assessment of menopausal symptoms may be greatly inuenced by the presence of or a history of a mood disorder that makes it dicult to disentangle the relationships between menopausal symptoms and other emotional or psychosocial problems. Transient increase in depressive symptoms related to menopausal status Cross-sectional population-based studies consistently report that the highest prevalence of depression occurs in women during the reproductive years [15]. Longitudinal studies of women during the menopausal transition have had conicting results, however. As part of the POAS, Freeman et al [16] published results of a longitudinal study of 436 women initially between the ages of 35 and 47 years and followed up for 4 years. They found an increase in depressive symptoms during the transition to menopause (particularly in the late transition) and improvement in depressive symptoms after menopause compared with premenopausal women. Independent of age and other factors associated with depression, women in the early transition were 55% more likely, and those in the late transition were almost 3 times more likely, to report signicant depressive symptoms compared with premenopausal women. As follicle-stimulating hormone (FSH) levels or age rose, the likelihood of depression decreased. The inverse association between FSH and depressive symptoms suggests that the changing hormonal

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milieu may contribute to a transient dysphoric mood during the transition. In this longitudinal cohort study, race (African American), unemployment, and hot ashes were associated with depression. The strongest predictors of depression were a history of depression (odds ratio [OR], 2.45; 1.613.72), poor sleep (OR, 2.95; 2.084.19), and severe premenstrual syndrome (OR, 3.8; 2.555.67). In another longitudinal study of 2103 women, Maartens et al [17] also found increased depressive symptoms in the transition from pre- to perimenopause and perimenopause to post menopause. Other factors related to depressive symptoms in their analysis included the following factors: unemployment, inability to work, nancial problems, death of a partner, death of a child, and previous depression.

Depressive symptoms related to vasomotor symptoms There is much evidence to indicate that depressive symptoms during the transition can be attributed to other factors, including vasomotor symptoms, rather than directly caused by the changing hormonal milieu. The strongest predictor of depressed mood associated with menopause is a history of depression, however, as demonstrated in most studies of dysphoric mood in the menopausal transition. The Massachusetts Womens Health Study found that whereas the perimenopause is associated with slightly increased depression, this association could be explained by increased reporting of vasomotor symptoms. This longitudinal study of 2565 women aged 45 to 55 years demonstrated a transitory increase in depression during the perimenopause, which improved after menopause. Women with prolonged transitions ([27 mo) were at greatest risk of depression compared with those with short transitions. With adjustment for vasomotor symptoms, however, the association with menopausal status was no longer signicant. Furthermore, the authors found that hot ashes, night sweats, and menstrual bleeding problems were independently associated with depression [18]. Similarly, results of the SWAN study demonstrated that depressive symptoms were associated with hot ashes/night sweats and trouble sleeping rather than with changes in hormones. The groups ndings support the idea that depression during this transition is caused by various factors rather than menopausal status alone [19]. Similarly, Dennerstein et al [20] published data from a longitudinal study of 354 women aged 45 to 55 years during the menopausal transition. The authors report indicated that psychosocial and lifestyle factors, together with health experience, have more eect on mood than endocrine changes. They failed to conrm the association between depression and menopausal status and instead found that overall mood scores improved over time. The authors found that vasomotor and somatic symptoms, self-rated health, feelings for a partner,

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marital status, and interpersonal stress signicantly aected mood over this period. Disrupted marriage, smoking, nulliparity, a history of premenstrual symptoms, mood swings, trouble sleeping, and memory problems have been associated with depression in middle-aged women in other studies [21]. Although some studies indicate that menopausal status is associated with a transient increase in depressive symptoms, most evidence indicates that depressive symptoms may be related primarily to other psychosocial and menopausal symptoms rather than menopausal status. Other emotional symptoms More recently, other emotional symptoms have gained attention because the association between depression and menopausal status has not been conrmed. Specically, some authors believe that too much emphasis has been placed on depression when symptoms of mood lability, irritability and nervousness may be more important during this period. As part of the SWAN study, two cross-sectional analyses were performed to identify characteristics of women in a multiethnic population who are at risk of psychologic symptoms during the transition. In the initial evaluation, they found that psychologic distress (irritability, depression, and tension) was greater in early perimenopausal women compared with pre- or postmenopausal women and was highest among whites compared with all other ethnic groups [22]. The follow-up cross-sectional study included 3161 women, and again conrmed the association between early premenopause and self-reported irritability, nervousness, and frequent mood changes on at least 6 days during the previous 2 weeks. In addition, women during the transition seemed to suer from more persistent symptoms compared with premenopausal women. These associations remained signicant even when the analysis was adjusted for vasomotor symptoms and sleep disturbances, factors believed to mediate the relationship between emotional symptoms and menopausal status. In this study, feeling blue was not associated with menopausal status. Of note, whites suered from more psychologic symptoms than the other ethnic groups, and women with less than a college education had signicantly higher odds of dysphoric mood during the perimenopause. Although these ndings are intriguing and help to broaden the investigation of emotional symptoms during the transition, the studies are limited by their minimal psychologic assessment [23].

Sleep In women, the prevalence of sleep problems increases dramatically during middle age. Among women between the ages of 45 and 49 years, 23.6%

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reported sleep diculties and 39.7% complained of such trouble by their early 50s [24]. Reported problems include trouble falling asleep, disturbed sleep, and frequent awakenings. This phenomenon has been largely attributed to changes that occur during menopause; however, studies have not had consistent results with respect to this issue. Sleep and menopausal status Most studies have found a link between self-reported sleep problems and menopause. Kuh et al [25] found that postmenopausal women were 3.4 times more likely to report trouble sleeping compared with premenopausal women. Women during the perimenopause had a smaller, but signicant likelihood of troubled sleep. Owen and Matthews [26] conducted a longitudinal study of self-reported insomnia during the menopausal transition. They found that menopausal women were more likely to report sleep problems. Findings from the SWAN study of a multiethnic community population indicate that peri- and postmenopausal women are more likely to report diculty sleeping over the past 2 weeks compared with premenopausal women. Other factors related to poor sleep include ethnicity, vasomotor and psychologic symptoms, self-perceived health, health behaviors, arthritis, and education [27]. There is some evidence to support a relationship between vasomotor symptoms and sleep disturbances. In 1981, Erlik et al [4] monitored sleep while recording nger temperature and skin resistance. The authors demonstrated a signicant correlation between the occurrence of hot ashes and waking episodes among menopausal women compared with premenopausal women. Other studies, however, have not found an association between sleep diculties and menopausal status after other age-related problems were taken into account. Depression, chronic pain, and other health-related conditions negatively aect sleep during this time during womens lives. The results from Baker et al [28] demonstrated an association between emotional symptoms (increased anxiety and decreased vigor) and sleep problems. Hormones and sleep disturbance Few investigators have examined the relationship between hormones and sleep disturbance during the transition. Preliminary evidence suggests that a decline in estradiol levels may be related to self-reported sleep disruption. As part of the POAS, a 2-year longitudinal analysis of sleep was conducted in 436 late-reproductive-aged women (aged 3547 y at baseline). This report explored the associations of subjective sleep quality with hormone levels and other clinical, behavioral, and demographic variables. Signicant independent associations with poor sleep included greater hot ashes, anxiety, depressive symptoms, caeine consumption, and lower estradiol levels in

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women aged 45 to 49 years. Other hormones (FSH, LH, testosterone, dihydroepiandrostenedione sulfate) were not signicantly associated with poor sleep. This report is unique and important because of its longitudinal assessment of hormones and mood and behavioral variables in women in their late 30s and 40s [29]. Further studies are needed to conrm the association between estradiol levels and sleep problems. Objective sleep measures Objective measures of sleep during the menopause recently have been conducted using polysomnography. Shaver and Zenk [30] assessed 17 sleepquality parameters with polysomnography in three groups of women of dierent menopausal status and could not demonstrate a signicant dierence in sleep quality. As part of the Wisconsin Sleep Cohort Study (WSCS), an ongoing population-based longitudinal study of sleep disorders, a cross-sectional study examined 589 women who underwent extensive interview and overnight polysomnography. Based on self-report questionnaires, both peri- and postmenopausal women were twice as likely to report that they were never or not usually satised with sleep compared with premenopausal women. Perimenopausal women were more likely to complain of diculty initiating sleep.Polysomnographic measures of sleep quality were not consistent with the womens self-reports of sleep, however. Sleep quality as assessed by the polysomnographic measures was not less favorable in peri- or postmenopausal women compared with the premenopausal women. Furthermore, postmenopausal women had the best sleep architecture, with less stage 1 sleep and more stage 3 and 4 sleep compared with premenopausal participants. In addition, these investigators found that even though women with sleep-related hot ashes were more likely to report dissatisfaction with sleep, no dierences in objective sleep quality were noted between women who did and did not report hot ashes. This study challenges the hypothesis that menopause diminishes sleep quality. Other factors likely explain the self-reported sleep diculties rather than menopausal status alone. The authors acknowledged that the contradictory associations of menopause with objective and subjective sleep quality emphasize the need to better understand the aspects of sleep reected by dierent measures. Sleep problems during the transition should not be attributed to hormonal changes alone but should prompt further investigation of other sleep-related disorders [31]. Sleep-disordered breathing Another report published by the WSCS demonstrated that the menopausal transition is associated with an increased likelihood of sleepdisordered breathing. Postmenopausal women were 3.5 times more likely to have 15 or more apnea and hypopnea events per hour compared with

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premenopausal women. Although disordered breathing was associated with worse sleep architecture in all women, postmenopausal women overall had better sleep architecture than did premenopausal women [32]. Evidence suggests that this disordered breathing is not related to vasomotor symptoms or estradiol levels [33]. Diculties of studying sleep problems involve several factors. The subjective nature of sleep quality makes it dicult to assess. Furthermore, current objective measures of sleep quality from polysomnography do not necessarily reect subjective sleep quality. In addition, it is dicult to control for the many factors during midlife that might potentially aect sleep. Retirement, job changes, empty nest syndrome, changing relationship with partner, death of a parent, and other stressors have been associated with sleep problems. As in other aspects of menopause research, longitudinal studies that include an assessment of sleep satisfaction at a premenopausal baseline are needed to evaluate change in sleep quality over the menopausal transition.

Sexual functioning Female sexual dysfunction is extremely prevalent in the United States, aecting more than 40% of women aged 18 to 59 years [34]. There is substantial evidence that sexual dysfunction increases through the menopausal transition [35,36]. Estimates of sexual dysfunction during the transition are as high as 88% [37]. There is relatively little research on the sexual problems of women, particularly their association with reproductive aging. In part, this lack of attention may be from the complexity of female sexuality, which is inuenced by various emotional, social, and physiologic factors [3539]. The menopausal transition is a time when signicant psychosocial and physiologic changes occur and concomitant illnesses arise. It is understandable that such major life changes inuence sexual functioning [39]. It is dicult to come to any clear conclusions regarding sexuality during the menopausal transition because the literature is so diverse. Studies dier dramatically with respect to patient population, research design, the assessment of female sexuality, and other potential determinants of sexual function. Nonetheless, the current authors have summarized the current evidence regarding the sexual changes that occur, the pathophysiology, the link between hormonal changes and sexuality, and other risk factors for sexual problems during this period. Characteristics Several investigators have attempted to characterize the types of sexual problems aecting women during the transition. A longitudinal study of 438 middle-aged Australian women using a validated questionnaire of sexual

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function assessed how specic characteristics of sexuality changed over the menopausal transition. This study conrmed a signicant overall decline in sexual functioning during the transition, which was particularly dramatic from early to late perimenopause and less so from late perimenopause to post menopause. Sexual responsivity declined over the entire transition period. In addition, libido, sexual frequency, positive feelings for the partner, and partners sexual performance decreased and vaginal dyspareunia increased in the late perimenopause [35]. Similar ndings from a report of 329 women aged 18 to 79 years attending a gynecology clinic revealed that, compared with premenopausal women, menopausal women reported a signicant decline in the frequency of sexual fantasy, foreplay, and intercourse while suering from more problems with vaginal lubrication and infection [40]. Pathophysiology Until recently, the decline in sexual function largely has been attributed to physical changes that occur in the genitourinary system after menopause. For instance, there is evidence that after menopause the physiologic sexual response is altered by decreased skin ushing, muscle tension, bartholin gland secretion, vaginal lubrication, clitoral reactivity, vaginal expansion and congestion, and uterine contractions with orgasm [41]. Communitybased studies of self-reported sexual function in postmenopausal women seem to be consistent with the physiologic ndings. For example, in one study, common problems reported by menopausal women with sexual diculties included decreased desire, vaginal dryness, and decreased clitoral sensitivity, orgasmic intensity, and orgasmic frequency [42]. Notably, physiologic studies of sexual responsiveness during the menopausal transition are lacking, and further studies are needed to conrm or refute these ndings based on self-report. Hormone links Although some of the physiologic changes that occur with sexual functioning are related to the decline in estrogen that follows menopause, sexual changes that occur early in the transition cannot be attributed to estrogen-related genitourinary atrophy. Circulating estrogen levels do not fall to their low postmenopausal levels until after the nal menstrual period [43]. Nonetheless, a longitudinal study of 438 middle-aged women demonstrated that lower scores on sexual functioning measures correlated with decreasing estradiol levels [37]. In the Massachusetts Womens Health Study, however, estradiol levels were related only to pain, not other aspects of sexual functioning [50]. In the POAS, estradiol levels were similar between women with and without a self-reported decline in libido in the early menopausal transition [38].

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The relationship between androgens and sexuality during the menopausal transition remains elusive. Coincident with decreasing sexual interest, circulating androgens decline during the late reproductive years, with levels of circulating androgens at age 45 approximately one-half that of women in their 20s [44]. It has been presumed that the age-related decline in androgens contributes to the decline in sexual function well before menopause. At any age, androgen insuciency is associated with low libido, loss of sexual desire, decreased sexual fantasy, decreased sensitivity to sexual stimulation, decreased arousability and capacity of orgasm, diminished vital energy and sense of well being, and loss of muscle tone [39]. Studies have not consistently been able to demonstrate that sexual dysfunction is related to decreased androgen levels in women during the menopausal transition, however [37,45]. Nonetheless, there is some evidence that testosterone supplementation to supraphysiologic levels improves sexual satisfaction in naturally and surgically menopausal women [4648]. At this point, the possible benets and risks of testosterone supplementation are not clear, and further research is needed. The POAS recently published preliminary data suggesting that the variability in total testosterone levels is associated with decreased libido during the late reproductive years. In this report, mean hormone values, hormone trends over 4 years, and uctuation in hormone levels were compared between women with and without a decrease in libido at the 4-year assessment period using multivariable logistic regression. Of 326 women, 87 (27%) reported a decreased libido whereas 239 (73%) did not. Subject-specic means for all hormone levels over the study period were similar between both groups. Women with the greatest uctuation in total testosterone over the study were more likely to report decreased libido, however. Specically, women whose testosterone levels uctuated from 3.8 to 21.5 ng/dL around a mean value of 9 ng/dL were 4 times more likely to report decreased libido compared with women with little uctuation in testosterone (OR, 4.0; 95% CI, 1.610.0). Limitations of this study include the limited assessment of sexual function and the lack of free testosterone measures, a more accurate measure of bioavailable testosterone compared with total testosterone [38]. Whether variability in androgens, rather than absolute level relates to sexual problems in women during this period needs further investigation. Other factors aecting sexual functioning Epidemiologic studies have highlighted other important factors aecting womens sexuality during the menopausal transition. In a prospective observational study, Dennerstein et al [49] found that feelings for partner and the partners sexual problems directly aected sexual functioning. In addition, social variables, such as paid work, interpersonal stress, daily hassles, and educational level, were signicantly related to sexual

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functioning. Other studies have found that health, marital status, mental health, and smoking have a signicant eect on womens sexual functioning [50]. Depression and children living at home also have been associated with decreased libido [38]. In summary, sexuality is an important aspect of health, which aects the overall well-being of all men and women. Many women suer from a decline in sexual function during the menopausal transition. Various factors seem to be involved in the sexual changes that occur during this time. Some of these include hormone changes, relationship issues, mental health, sociocultural inuences, and medical illnesses. The complexity of this area makes it extremely challenging to investigate. Current studies are limited by methodologic problems, including lack of validated measures of sexual functioning, small sample sizes, and insuciently sensitive hormone assays. Recently, the International Consensus Development Conference on Female Sexual Dysfunctions classied sexual dysfunction into four major categories: desire disorders, arousal disorders, orgasmic disorders, and sexual pain disorders [51]. Validated measures of sexual functioning that correspond with this new classication system exist and should be used to investigate specic areas of dysfunction. Again, longitudinal studies with the ability to take baseline subject characteristics into account are preferable to cross-sectional studies. Finally, studies must adequately measure various psychosocial factors aecting sexual functioning so that these can be adjusted for in the analysis. Much work must be done to better understand the causes of sexual problems during the menopausal transition so that better treatments can be developed.

Summary The transition to menopause marks a critical time of profound change in a womans life. Hormonal, physiologic, and psychosocial factors are in ux. Acute symptoms of hot ashes, sleep disruption, psychologic symptoms, and decreased sexual functioning may accompany these biologic and psychosocial changes. Contrary to common beliefs, these symptoms can begin early in the menopausal transition during the late reproductive years, well before menstrual irregularities occur. Importantly, studies show that these acute symptoms are multifactorial in nature, with biologic changes interacting with other psychologic, cultural, and socioeconomic characteristics of women. Inasmuch as womens experience of menopause varies widely, the severity of menopausal symptoms cannot be attributed solely to the changing reproductive hormonal milieu that denes the transition to menopause. It is important for clinicians to understand the complexity of acute menopausal symptoms. It is not sucient to attribute these complaints to menopause (or to dismiss them as not related to menopause) but rather to

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provide treatment options for relief of the symptoms and recognize when further investigation is warranted. Most important, the clinician must determine whether these symptoms are primarily associated with the menopausal transitionand are thus likely to be time-limitedor whether the symptoms represent manifestations of underlying medical or psychiatric illnesses. In addition, this is an ideal time to re-evaluate a womans psychosocial history to determine whether she has an adequate support system to deal with life stressors. The clinician should have a wide understanding of changes that occur during the transition to maximize womens health and well-being. Finally, further epidemiologic and basic research must be done to better understand changes that occur during the transition to menopause. Longitudinal studies with sample sizes sucient for statistical validity, appropriate hormone measurement, and validated instruments to assess menopausal symptoms and potential confounders are needed to further disentangle the complex relationships between hormones and symptoms and other factors that mediate these relationships.

References
[1] McKinlay SM, Jeerys M. The menopausal syndrome. Br J Prev Soc Med 1974;28:10815. [2] Freedman RR. Physiology of hot ashes. Am J Hum Biol 2001;13:45364. [3] Kronenberg F. Hot ashes: epidemiology and physiology. Ann N Y Acad Sci 1990;592: 5286. [4] Erlik Y, Tatryn IV, Meldrum DR, Lomax P, Bajorek JF, Judd HL. Association of waking episodes with menopausal hot ushes. JAMA 1981;245:17414. [5] McKinlay SM, Brambilla DJ, Posner JG. The normal menopause transition. Maturitas 1992;14:10315. [6] Feldman BM, Voda A, Gronseth E. The prevalence of hot ash and associated variables among perimenopausal women. Res Nurs Health 1985;8:2618. [7] Gold EB, Sternfeld B, Kelsey JL, et al. Relation of demographic and lifestyle factors to symptoms in a multi-racial/ethnic population of women 4055 years of age. Am J Epidemiol 2000;152:46373. [8] Dennerstein L, Smith AM, Morse C, Burger H, Green A, Hopper J, et al. Menopausal symptoms in Australian women. Med J Aust 1993;159:2326. [9] Freeman EW, Grisso JA, Berlin J, Sammel M, Garcia-Espana B, Hollander L. Symptom reports from a cohort of African American and white women in the late reproductive years. Menopause 2001;8:3342. [10] Freedman RR. Core body temperature variation in symptomatic and asymptomatic postmenopausal women: brief report. Menopause 2002;9:399401. [11] Avis NE, Stellato R, Crawford S, et al. Is there a menopausal syndrome? Menopausal status and symptoms across racial/ethnic groups. Soc Sci Med 2001;52:34556. [12] Beyene Y. Cultural signicance and physiological manifestations of menopause: a bicultural analysis. Cult Med Psychiatry 1986;10:4771. [13] Tang GW. The climacteric of Chinese factory workers. Maturitas 1994;19:17782. [14] Woods NF, Mariella A, Mitchell ES. Patterns of depressed mood across the menopausal transition: approaches to studying patterns in longitudinal data. Acta Obstet Gynecol Scand 2002;81:62332.

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[15] Blazer DG, Kessler RC, McGonagle KA, Swartz MS. The prevalence and distribution of major depression in a national community sample: the National Comorbidity Survey. Am J Psychiatry 1994;151:97986. [16] Freeman EW, Sammel MD, Liu L, et al. Hormones and menopausal status as predictors of depression in women in transition to menopause. Arch Gen Psychiatry 2004;61:6270. [17] Maartens LWF, Knottnerus JA, Pep VJ. Menopausal transition and increased depressive symptomatology: a community based prospective study. Maturitas 2002;42:195200. [18] Avis E, Brambilla E, McKinlay SM, Vass K. A longitudinal analysis of the association between menopause and depression. Ann Epidemiol 1994;4:21420. [19] Avis NE, Crawford S, Stellato R, Longcope C. Longitudinal study of hormone levels and depression among women transitioning through the menopause. Climacteric 2001;4:2439. [20] Dennerstein L, Lehert P, Burger H, Dudley E. Mood and the menopausal transition. J Nerv Ment Dis 1999;187:68591. [21] Harlow BL, Cohen L, Otto MW, Spiegelman D, Cramer DW. Prevalence and predictors of depressive symptoms in older premenopausal women. Arch Gen Psychiatry 1999;56: 41824. [22] Bromberger JT, Meyer PM, Kravitz HM, et al. Psychologic distress and natural menopause: a multiethnic community study. Am J Public Health 2001;91:143542. [23] Bromberger JT, Assmann SF, Avis NE, Schocken M, Kravitz HM, Cordal A. Persistent mood symptoms in a multiethnic community cohort of pre and perimenopausal women. Am J Epidemiol 2003;158:34756. [24] Cirignotta F, Mondini S, Zucconi M, Lenzi PL, Lugaresi E. Insomnia: an epidemiological survey. Clin Neuropharmacol 1985;8:S4954. [25] Kuh DL, Wadsworth M, Hardy R. Womens health in midlife: the inuence of the menopause, social factors and health in earlier life. Br J Obstet Gynaecol 1997;104:92333. [26] Owen JF, Matthews KA. Sleep disturbance in healthy middle-aged women. Maturitas 1998; 30:4150. [27] Kravitz HM, Ganz PA, Bromberger J, Powell LH, Sutton-Tyrrel K, Meyer PM. Sleep diculty in women at midlife: a community survey of sleep and the menopausal transition. Menopause 2003;10:1928. [28] Baker A, Simpson S, Dawson D. Sleep disruption and mood changes associated with menopause. J Psychosom Res 1997;43:35969. [29] Hollander LE, Freeman EW, Sammel MD, Berlin JA, Grisso JA, Battistini M. Sleep quality, estradiol levels and behavioral factors in late reproductive age women. Obstet Gynecol 2001;98:3917. [30] Shaver JLF, Zenk SN. Sleep disturbance in menopause. J Womens Health Gend Based Med 2000;9:10918. [31] Young T, Rabago D, Zgierska A, Austin D, Finn L. Objective and subjective sleep quality in premenopausal, perimenopausal, and postmenopausal women in the Wisconsin Sleep Cohort Study. Sleep 2003;26:66772. [32] Young T, Finn L, Austin D, Peterson A. Menopausal status and sleep-disordered breathing in the Wisconsin Sleep Cohort study. Am J Respir Crit Care Med 2003;167:11815. [33] Polo-Kantola P, Rauhala E, Saaresranta T, Aittokallio T, Erkkola R, Polo O. Climacteric vasomotor symptoms do not predict nocturnal breathing abnormalities in postmenopausal women. Maturitas 2001;39:2937. [34] Laumann EO, Paik A, Rosen RC. Sexual dysfunction in the United States: prevalence and predictors. JAMA 1999;281:53744. [35] Dennerstein L, Dudly E, Burger H. Are changes in sexual functioning during midlife due to aging or menopause? Fertil Steril 2001;76:45660. [36] Osborn M, Hawton K, Gath D. Sexual dysfunction among middle-aged women in the community. BMJ 1988;296:95962. [37] Dennerstein L, Randolph J, Tae J, Dudley E, Burger H. Hormones, mood, sexuality, and the menopausal transition. Fertil Steril 2002;77:S428.

C.R. Gracia, E.W. Freeman / Endocrinol Metab Clin N Am 33 (2004) 675689

689

[38] Gracia CR, Sammel MD, Freeman E, Liu L, Hollander L, Nelson DB. Predictors of decreased libido in women during the late reproductive years. Menopause 2004;11:14450. [39] Palacios S, Robar AC, Menendez C. Sexuality in the climacteric years. Maturitas 2002;43: S6977. [40] Rosen RC, Taylor JF, Leiblum SR, Bachmann GA. Prevalence of sexual dysfunction in women: results of a survey study of 329 women in an outpatient gynecological clinic. J Sex Marital Ther 1993;19:171. [41] Masters WH, Johnson VE. Human sexual response. Boston: Little, Brown; 1966. [42] Sarrel PM. Sexuality and menopause. Obstet Gynecol 1990;75:26s. [43] Burger H, Dudley E, Hopper J, et al. Prospectively measured levels of serum FSH, estradiol, and the dimeric inhibins during the menopausal transition in a population-based cohort of women. J Clin Endocrinol Metab 1999;84:402530. [44] Zumo B, Strain GW, Miller LK, Rosner W. Twenty four hour mean plasma testosterone concentration declines with age in normal premenopausal women. J Clin Endocrinol Metab 1995;80:142930. [45] Guay AT, Jacobson J. Decreased free testosterone and dehydroepiandrosterone-sulfate levels in women with decreased libido. J Sex Marital Ther 2002;28:12942. [46] Davis SR, McCloud PI, Strauss BSG, Burger H. Testosterone enhances estradiol eects on postmenopausal bone density and sexuality. Maturitas 1995;21:22736. [47] Sarrel PM, Dobay B, Wiita B. Sexual behavior and neuroendocrine response in estrogen and estrogen-androgen replacement in postmenopausal women dissatised with estrogen-only therapy. J Reprod Med 1998;43:84756. [48] Shifren JL, Braunstein GD, Simon JA, et al. Transdermal testosterone treatment in women with impaired sexual function after oophorectomy. N Engl J Med 2000;343:6828. [49] Dennerstein L, Lehert P, Burger H, Dudley E. Factors aecting sexual functioning of women in the mid-life years. Climacteric 1999;2:25462. [50] Avis NE, Stellato R, Crawford S, Johannes C, Longcope C. Is there an association between menopause status and sexual functioning? Menopause 2000;7:297309. [51] Basson R, Berman J, Burnett A, Derogatis L, Ferguson D, Fourcroy J, et al. Report of the international consensus development conference on female sexual dysfunction: denitions and classications. J Urol 2000;163:8889.