Jeanne Leventhal Alexander

The effects of postmenopausal hormone therapies on female sexual functioning: a review of double-blind, randomized controlled trials

Double-blind randomized controlled trials of estrogen and/or testosterone on sexual function among natural or surgical menopause in women are reviewed. Power, validity, hormone levels, and methodological issues were examined. Certain types of estrogen therapy were associated with increased frequency of sexual activity, enjoyment, desire, arousal, fantasies, satisfaction, vaginal lubrication, and feeling physically attractive, and reduced dyspareunia, vaginal dryness, and sexual problems. Certain types of testosterone therapy (combined with estrogen) were associated with higher frequency of sexual activity, satisfaction with that frequency of sexual activity, interest, enjoyment, desire, thoughts and fantasies, arousal, responsiveness, and pleasure. Whether specific serum hormone levels are related to sexual functioning and how these group effects apply to individual women are unclear. Other unknowns include long-term safety, optimal types, doses and routes of therapy, which women will be more likely to benefit from (or be put at risk), and the precise interplay between the two sex hormones.

A symptomatic approach to understanding women's health experiences: a cross-cultural comparison of women aged 20 to 70 years.

Objectives:To determine patterns of symptoms across age groups, identify symptom groups associated with ovarian hormonal depletion or other variables, and develop a prediction model for each symptom. Design:This was a cross-sectional survey of 4,517 women ages 20 to 70 years recruited from market research panels in the United States, United Kingdom, Germany, France, and Italy using a self-report questionnaire that included general health information and a checklist of 36 symptoms. Stepwise regression was used to determine for each symptom how prevalence varied with age, indicators of menopausal hormonal changes, and the effects of other explanatory variables, including body mass index, morbidity, and country. Hierarchical clustering was used to group symptoms. Results:Six groups of symptoms were found, of which two groups, with seven symptoms in total, were related to markers of menopausal hormonal change: a group consisting of hot flashes and night sweats and a second group including poor memory; difficulty sleeping; aches in the neck, head, and shoulders; vaginal dryness; and difficulty with sexual arousal. Physical and mental morbidity affected estimates of the prevalence of all symptoms. Psychological symptoms declined with age from a maximum prevalence before age 40. Certain physical symptoms increased with age and body mass index. Clustering identified three country groups: (1) US and UK women; (2) French and Italian women; and (3) German women. There were marked differences in prevalence between countries for certain physical and psychological symptoms. Conclusions:The seven symptoms most linked to menopausal hormonal change should form part of any future menopause symptom list. Physical and mental morbidity affect symptom prevalence and should be measured.

Nomenclature and endocrinology of menopause and perimenopause

The early and late perimenopausal transition is characterized by changing cycle length as well as by menopausal symptoms in some women, including increasing hot flashes and night sweats. Breast tenderness decreases as women enter the late transition. This review, as part of the clinical reviews on the menopausal woman with comorbidity, covers the endocrine phenomena of perimenopause, terminology and the observed clinical characteristics of the transition. It should be noted that the definitions covering this period vary between publications. The average duration of perimenopause is approximately 5 years. The earliest detectable hormonal change is a fall in ovarian secretion of inhibin B, with a subsequent rise in follicle-stimulating hormone and maintained or increased levels of estradiol. As women transit the perimenopause, cycle irregularity increases, with the more frequent occurrence of prolonged ovulatory and anovulatory cycles. Levels of follicle-stimulating hormone and estradiol fluctuate increasingly and luteal function declines. Vasomotor symptoms tend to be most frequent around the time of final menses. The perimenopause is thus a time of cycle and hormone variability and single hormone measurements provide little useful information, with the clinical history being the most appropriate method of assessing menopausal status. This information will be very helpful to the clinician treating the concerned and symptomatic patient. It will also aid clinicians to avoid unnecessary laboratory testing and help them educate their patients about their perimenopause.

Women, anxiety and mood: a review of nomenclature, comorbidity and epidemiology

Women experience a high prevalence of mood and anxiety disorders, and comorbidity of mood and anxiety disorders is highly prevalent. Both mood and anxiety disorders disturb sleep, attention and, thereby, cognitive function. They result in a variety of somatic complaints. The mood disorder continuum includes minor depression, dysthymia, major depression and bipolar disorder. Chronobiological disorders, such as seasonal affective disorder as well as premenstrual dysphoric disorder, occur in some women, with comorbid seasonal affective disorder and premenstrual dysphoric disorder in just under half of these individuals 1. Early life experience, heritability, gender, other psychiatric illness, stress and trauma all interact dynamically in the development of mood and anxiety disorders. The epidemiology, nomenclature and clinical diagnostic issues of these illnesses in midlife woman are reviewed.

Testosterone and libido in surgically and naturally menopausal women

The assessment and then treatment of a change in libido, or a change in the desire to partake in sexual activity, during the menopausal transition and beyond has been a challenging and elusive area of clinical research. This is partly due to the multidimensional nature of female sexuality, the difficulties of measuring testosterone in women in a reliable and accurate manner, and the complexity of the neurobiology and neurobehavior of female sexual desire. In addition, there is a lack of evidence for diagnostic specificity of low free testosterone levels for the symptom of low libido in women for whom there are no confounding interpersonal or psychological factors; although, in the symptomatic population of surgically or naturally menopausal women, a low level of free testosterone often accompanies a complaint of reduced desire/libido. The randomized clinical trial research on testosterone replacement for naturally and/or surgically menopausal women with sexual dysfunction has been criticized for a high placebo response rate, supraphysiological replacement levels of testosterone, the perception of modest clinical outcome when measuring objective data such as the frequency of sexual intercourse relative to placebo, and the unknown safety of long-term testosterone replacement in the estrogen-replete surgically or naturally menopausal woman. A careful review of current evidence from randomized, controlled trials lends support to the value of the replacement of testosterone in the estrogen-replete menopausal woman for whom libido and desire has declined. The issue of long-term safety remains to be answered.

Role of stressful life events and menopausal stage in wellbeing and health.

Stress plays an essential role in the development, continuation and exacerbation of mood problems throughout a woman’s life. It exacerbates somatic symptoms of menopause, increasing the risk of recurrence of mood disorders, as well as of a mood disorder de novo throughout the lifespan and specifically in the menopausal transition. Chronic stress affects the hypothalamic–pituitary axis, hypothalamic–pituitary–ovarian axis, the proinflammatory cytokines and cardiovascular risk. The current evidence for the potential interactions between acute stress, chronic stress, childhood stress and victimization, and individual susceptibility to the development of depression and/or anxiety in response to stressful life events, are reviewed in the context of the increasing data on the association of these and a symptomatic menopausal transition. Strategies for the optimal approach for clinicians to evaluate and treat the symptomatic perimenopausal patient with stressful life events and comorbid mood disorders are presented.

Arthralgias, bodily aches and pains and somatic complaints in midlife women: etiology, pathophysiology and differential diagnosis

Somatic symptoms characterized by arthralgias, bodily aches and pains, musculoskeletal pain and joint pain have been investigated in a number of menopause and depression studies. Although depression is one of the most common causes of bodily aches and pains, and arthralgias, these same symptoms are also commonly associated with a natural menopause, surgical menopause and menopause induced by chemotherapy in breast cancer treatment. Somatic symptoms in the absence of definitive medical diagnoses result in these patients receiving various diagnoses and labels –‘medically unexplained symptoms’, ‘worried well’, as well as various Diagnostic and Statistical Manual of Mental Disorders (4th edition) somatoform diagnoses. Osteoarthritis and joint pain increase in prevalence from premenopausal- to menopausal-aged women with hormonal change implicated in their etiology. The current research on the relationships among menopause, depression, nociceptive mechanisms, perception and pain in the distressed midlife patient is discussed. The amelioration and management of pain symptoms in the menopausal and postmenopausal woman, with or without comorbid depression, have been elusive and difficult problems for clinicians. Familiarity with the differential diagnosis, pathophysiology and evidence-based treatment for such patients is crucial to their proper care.

Neurobehavioral impact of menopause on mood

The menopausal transition is a time of risk for mood change ranging from distress to minor depression to major depressive disorder in a vulnerable subpopulation of women in the menopausal transition. Somatic symptoms have been implicated as a risk factor for mood problems, although these mood problems have also been shown to occur independently of somatic symptoms. Mood problems have been found to increase in those with a history of mood continuum disorders, but can also occur de novo as a consequence of the transition. Stress has been implicated in the etiology and the exacerbation of these mood problems. Estrogen and add-back testosterone have both been shown to positively affect mood and well-being. In most cases, the period of vulnerability to mood problems subsides when the woman’s hormonal levels stabilize and she enters full menopause.

Assessment and treatment for insomnia and fatigue in the symptomatic menopausal woman with psychiatric comorbidity.

Studies and treatments for the symptomatic menopausal woman with sleep complaints have been reviewed elsewhere. This article, as part of the clinical review series on the comorbid symptomatic menopausal woman, aims to examine the evidence for diagnosis and treatment of women who present with distressing sleep symptoms that they attribute to menopause. The etiology of these symptoms may be a psychiatric disorder, a pre- or co-existing problem with sleep, or a dynamic interaction among one of these and/or a symptomatic menopause. The relationship between sleep disturbance and cognitive complaints, mood problems, fatigue and low energy will be reviewed. The new research on sleep, clinical consequences of insomnia of various types, the impact of sleep disturbance on morbidity and functioning – in the context of the midlife woman in the menopausal transition – will be explored along with the evidence for different treatment strategies for these sleep problems.

Impact of clinician and patient attitudes on clinical decision making for the symptomatic menopausal woman with or without comorbidity.

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.