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. Multifactorial nature of female sexuality 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. There is a lack of evidence for the diagnostic specificity of low free testosterone levels for the symptom of low libido in the 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 [1–6]. Female sexuality is dependent on biological, psychosexual, sociocultural and context-related factors [7–9]. As a consequence, any movement or change in any of these realms may increase or decrease a woman's perception of her drive or motivation to participate in sexual activity. The presence of any chronic medical illness such as diabetes, pulmonary or cardiovascular problems, or depression will in many instances impact a woman's sexuality concurrent with changes related to age [10,11]. The length of the relationship with a partner, as well as aging, has been demonstrated to impact sexual interest and frequency of sexual activity [12,13]. The menopause has been shown to have an incremental effect on a woman's sexuality, separate from the change brought about by aging [14]. The quality of her intimate relationship and the degree to which she feels empowered in it have been demonstrated to affect sexual desire [15]. The culture in which she lives has been shown to affect frequency of sexual intercourse [16]. The degree of stress she is under, as well as her general wellbeing, has also been shown to affect her libido. A recent longitudinal study demonstrated that higher stress lowers wellbeing, resulting in a decrease in sexual arousal, enjoyment, orgasm and desire [17]. In addition, the balance between sexual inhibition and sexual excitement may be unique to each woman and may change according to her circumstances, along with any other change she may have with regard to these opposing forces [18]. Thus, the treatment of any woman distressed by a change in desire at midlife and beyond is driven by many factors. The clinician's task is to elucidate which one or more of these many variables changed in her life, concurrent with her change in sexual desire, and then to determine whether or not these changes are related to her change in sexual desire

The value of follicle-stimulating hormone concentration and clinical findings as markers of the late menopausal transition

CONTEXT: The Stages of Reproductive Aging Workshop proposed bleeding and hormonal criteria for the menopausal transition, but operational definitions of hormone parameters were not specified. OBJECTIVE: This paper investigates the longitudinal relationship of annual serum FSH levels with four proposed bleeding criteria for the late menopausal transition in two cohort studies. The goal is to provide empirically based guidance regarding application of hormonal criteria that may be optimal for widespread application in clinical and research settings for assessing menopausal stage. DESIGN/SETTING: Prospective menstrual calendar and annual serum FSH data were collected from two population-based cohort studies: the Melbourne Women\u27s Midlife Health Project and the Study of Women\u27s Health Across the Nation. PARTICIPANTS: Participants in the study were 193 Melbourne Women\u27s Midlife Health Project and 2223 Study of Women\u27s Health Across the Nation women aged 42-57 yr at baseline who contributed 10 or more menstrual cycles and at least one annual serum FSH value. MAIN OUTCOME MEASURE(S): Association between bleeding criteria for the late menopausal transition and FSH was a main outcome measure. Associations of bleeding criteria, FSH, and hot flashes with the final menstrual period were also measured. RESULTS: A single FSH measure is an independent marker of the late menopausal transition, but FSH concentrations are less predictive of menopausal stage than any of four proposed bleeding criteria. Criterion FSH values for the late transition are similar across both studies. Experience of hot flashes adds no information in the presence of hormonal and bleeding criteria. CONCLUSIONS: An annual serum FSH concentration of 40 IU/liter could be incorporated, in conjunction with bleeding markers, into the Stages of Reproductive Aging Workshop paradigm for markers of the late menopausal transition

ISPMD consensus on the management of premenstrual disorders

The second consensus meeting of the International Society for Premenstrual Disorders (ISPMD) took place in London during March 2011. The primary goal was to evaluate the published evidence and consider the expert opinions of the ISPMD members to reach a consensus on advice for the management of premenstrual disorders. Gynaecologists, psychiatrists, psychologists and pharmacologists each formally presented the evidence within their area of expertise; this was followed by an in-depth discussion leading to consensus recommendations. This article provides a comprehensive review of the outcomes from the meeting. The group discussed and agreed that careful diagnosis based on the recommendations and classification derived from the first ISPMD consensus conference is essential and should underlie the appropriate management strategy. Options for the management of premenstrual disorders fall under two broad categories, (a) those influencing central nervous activity, particularly the modulation of the neurotransmitter serotonin and (b) those that suppress ovulation. Psychotropic medication, such as selective serotonin reuptake inhibitors, probably acts by dampening the influence of sex steroids on the brain. Oral contraceptives, gonadotropin-releasing hormone agonists, danazol and estradiol all most likely function by ovulation suppression. The role of oophorectomy was also considered in this respect. Alternative therapies are also addressed, with, e.g. cognitive behavioural therapy, calcium supplements and Vitex agnus castus warranting further exploration

Women's Sexual Functioning, Lifestyle, Mid-age and Menopause in 12 European countries.

To investigate the relative effects of hormonal and relationship factors on female sexual function during the natural menopausal transition. Design was Prospective population-based questionnaire study. Setting: Interviews were conducted in the patients' homes. Patient(s): 1458 women from 12 european countries aged 45–55 years who were still menstruating at baseline. Hormonal levels, age, menopausal status, partner status, and feelings for partner were measured and evaluated with longitudinal structural equation modeling. Main Outcome Measure(s): Short personal experiences questiom

Modelling mid-aged women's sexual functioning: A prospective, population-based study.

Four hundred thirty-eight Australian-born women aged 45–55 years who were still menstruating at baseline. Eight years of longitudinal data were available for 336 of these women, none of whom were hysterectomized. Hormonal levels, age, menopausal status, partner status, and feelings for partner were measured and evaluated with longitudinal structural equation modeling. Sexual response was predicted by prior level of sexual function, change in partner status, feelings for partner, and E2 level (R2 = .65); dyspareunia was predicted by prior level of dyspareunia and E2 level (R2 = .53); and frequency of sexual activities was predicted by prior level of sexual function, change in partner status, feelings for partner, and level of sexual response (R2 = .52). The minimum effective dose needed to increase sexual response by 10% (700 pmol/L E2) is twice that needed to decrease dyspareunia

New Statistical Developments for the analysis of changes in longitudinal studies of medical cohort patients: The particular aspect of Structural Equation Modeling

A comprehensive review of techniques to study cohorts exposed different types of techniques, including Summary statistics techniques, Multivariate analysis of Variance, Autocorrelation Time series and ARMA techniques, and Simultaneous Equation Models. a) Summary statistics are probably the most simple and evident techniques to assess menopause effects in comparing states between pre-peri and post menopausal phases. b) Although ARMA like time series techniques proved very useful, , their use remains was found limited in this application where only 8 years are available, and where only rend trend tendency is expected. b) Multivariate Technique such as MANOVA are very performant when within time subject follows the experiment. Conclusion: The Partial First Order Instantaneous Markov model is probably the most appropriat e, and is characterized by the simple equation yt=ayt-1 + ?bj xit + e. Thus, Yt is influenced by the last value yt-1 and a combination of variables but only at time T. ThCet article a envisage une comparaison méthodologique de diverses methodes statistiques destinées à l'examen prospectif du veillissement humain, en particulier l'étude des repercussion de la transition ménopausique. On a examiné les techniques d'aggrégation simple; l'analyse multivariée de la variance, les modèles à autocorrelation, les techniques ARMA, et la modélisation structurelle. Les techniques d'aggrégation sont les plus simples et conviennent dans une majorité de problèmes, mais sont généralement plus adéquats dans des schemas observationnels. Les techniques ARMA sont généralement peu applicables, car les données dépassent généralement peu 8 années consecutives. Le modèle MANOVA est généralement satisfaisant pour des experimentations non observationnelles. Conclusion: Le modèle partiel de Markov du premier ordre yt=ayt-1 + ?bj xit + e. apparait probablement comme le plus realiste, en tenant compte d'une part des composantes génétiques initiales, d'autre part permet de tenir e

Time to the final menstrual period

Objective: To determine, for a woman aged >45 years, whether selected hormonal, health status, and demographic measures are related to the time to final menstrual period (FMP) from a point where 6 weeks separate the shortest and longest cycles experienced to date. Design: Cohort study. Setting: Volunteers in an academic research environment. Patient(s): Ninety-nine menstruating women aged 46 years to 55 years on entry completed menstrual diaries, gave annual blood samples, and were interviewed annually. They were observed for a mean period of 1.5 years. Seventy-seven reached FMP during observation. Intervention(s): None. Main Outcome Measure(s): Time to reach FMP from the date of a marker event—the difference between the longest and shortest of recent cycles reaching 6 weeks. Result(s): Women self-rating as in the transition have a greater “hazard” or probability of FMP at any time after the marker event. Allowing for this and other covariates, the hazard is estimated to increase by 30% (confidence interval [CI]: 10%, 60%) for each year of age and 50% (CI: 7%, 118%) for each unit increase in log FSH, measured at the time of the marker event. Conclusion(s): For women aged >45 years, the time remaining in the menopausal transition from the day on which ≥6 weeks separate the longest and shortest recent cycles is related to self-rating of menopausal status and to serum FSH level. The median number of months remaining ranges from 11 for those with FSH of >20 IU/L and who see themselves as in transition to 21 months for those with lower FSH and who notice little evidence of being in transition

The menopausal transition and quality of life: methodologic issues

The methodology in studies of the menopausal transition involves a consideration of social, statistical, and psychometric issues. Social issues are relevant on two levels. One is based upon principles of good practice in research on women and health that have been articulated at the international level. The other social level involves a consideration of the aims of the study and how these aims are implemented in the measures that are used, both for the symptoms of menopause and for the quality of life of the women involved in the research. We review the basic principles and issues related to sampling of population studies, physiological changes, and measurement of quality of life. Three recent measures of quality of life designed for studies of the menopause are then briefly reviewed

Menstrual patterns leading to the final menstrual period

OBJECTIVE: To characterize premenopausal menstrual regularity and the patterns of divergence from regularity associated with the approach of the final menstrual period. DESIGN: 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." RESULTS: 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. CONCLUSIONS: 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