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A 54-year-old woman presents with low libido, diminished arousal, and anorgasmia. She had undergone a hysterectomy and bilateral salpingo-oophorectomy at 49 years of age owing to menorrhagia and a family history of ovarian cancer. She has been using transdermal estradiol patches and topical vaginal estradiol and has no meno-pausal symptoms or dyspareunia. She is in a loving relationship with no major life stressors, does not have depression, and takes no other medication. All other clinical characteristics, including her weight and blood pressure, are normal. She has recently become aware that there may be treatment options for low libido and would like to discuss these with you. How would you respond? [ABSTRACT FROM AUTHOR]

Menopause is the cessation of ovarian function, with loss of reproductive hormone production and irreversible loss of fertility. It is a natural part of reproductive aging. The physiology of the menopause is complex and incompletely understood. Globally, menopause occurs around the age of 49 years, with geographic and ethnic variation. The hormonal changes of the menopause transition may result in both symptoms and long-term systemic effects, predominantly adverse effects on cardiometabolic and musculoskeletal health. The most effective treatment for bothersome menopausal symptoms is evidence-based, menopausal hormone therapy (MHT), which reduces bone loss and may have cardiometabolic benefits. Evidence-based non-hormonal interventions are also available for symptom relief. Treatment should be individualized with shared decision-making. Most MHT regimens are not regulator approved for perimenopausal women. Studies that include perimenopausal women are needed to determine the efficacy and safety of treatment options. Further research is crucial to improve menopause care, along with research to guide policy and clinical practice. Menopause is a natural part of reproductive aging affecting roughly half the world's population. This review summarizes the biology and life consequences of menopause, the role of supportive care, menopause-specific therapeutic options, and future research directions that are needed to achieve better menopause care. [ABSTRACT FROM AUTHOR]

BACKGROUND The early onset of menopause is associated with increased risks of cardiovascular disease and osteoporosis. As a woman's circulating anti-Müllerian hormone (AMH) concentration reflects the number of follicles remaining in the ovary and declines towards the menopause, serum AMH may be of value in the early diagnosis and prediction of age at menopause. OBJECTIVE AND RATIONALE This systematic review was undertaken to determine whether there is evidence to support the use of AMH alone, or in conjunction with other markers, to diagnose menopause, to predict menopause, or to predict and/or diagnose premature ovarian insufficiency (POI). SEARCH METHODS A systematic literature search for publications reporting on AMH in relation to menopause or POI was conducted in PubMed®, Embase®, and the Cochrane Central Register of Controlled Trials up to 31 May 2022. Data were extracted and synthesized using the Synthesis Without Meta-analysis for diagnosis of menopause, prediction of menopause, prediction of menopause with a single/repeat measurement of AMH, validation of prediction models, short-term prediction in perimenopausal women, and diagnosis and prediction of POI. Risk-of-bias was evaluated using the Tool to Assess Risk of Bias in Cohort Studies protocol and studies at high risk of bias were excluded. OUTCOMES A total of 3207 studies were identified, and 41, including 28 858 women, were deemed relevant and included. Of the three studies that assessed AMH for the diagnosis of menopause, one showed that undetectable AMH had equivalent diagnostic accuracy to elevated FSH (>22.3 mIU/ml). No study assessed whether AMH could be used to shorten the 12 months of amenorrhoea required for a formal diagnosis of menopause. Studies assessing AMH with the onset of menopause (27 publications [n = 23 835 women]) generally indicated that lower age-specific AMH concentrations are associated with an earlier age at menopause. However, AMH alone could not be used to predict age at menopause with precision (with estimates and CIs ranging from 2 to 12 years for women aged <40 years). The predictive value of AMH increased with age, as the interval of prediction (time to menopause) shortened. There was evidence that undetectable, or extremely low AMH, may aid early diagnosis of POI in young women with a family history of POI, and women presenting with primary or secondary amenorrhoea (11 studies [n = 4537]). WIDER IMPLICATIONS The findings of this systematic review support the use of serum AMH to study the age of menopause in population studies. The increased sensitivity of current AMH assays provides improved accuracy for the prediction of imminent menopause, but diagnostic use for individual patients has not been rigorously examined. Prediction of age at menopause remains imprecise when it is not imminent, although the finding of very low AMH values in young women is both of clinical value in indicating an increased risk of developing POI and may facilitate timely diagnosis. [ABSTRACT FROM AUTHOR]

Every woman who lives past midlife will experience menopause, which, by definition, is complete cessation of ovarian function. This process might occur spontaneously (natural menopause) or be iatrogenic (secondary menopause), and can be further classified as 'early' if it occurs before the age of 45 years and 'premature' if it occurs before the age of 40 years. Globally, the mean age of natural menopause is 48.8 years, with remarkably little geographic variation. A woman's age at menopause influences health outcomes in later life. Early menopause is associated with a reduced risk of breast cancer, but increased risks of premature osteoporosis, cardiovascular disease and premature death. The cardinal symptoms of menopause, and adverse health sequelae, are due to loss of ovarian oestrogen production. Consequently, menopausal hormone therapy (MHT) that includes oestrogen or an oestrogenic compound ameliorates menopausal symptoms, while preventing menopause-associated bone loss and cardiometabolic changes. Importantly, comprehensive care of postmenopausal women involves lifestyle optimization (attention to nutrition and physical activity, reducing alcohol consumption and not smoking) and treating other established chronic disease risk factors. This Review offers a commentary specifically on the contemporary use of MHT and novel pharmaceutical alternatives to manage menopausal symptoms. [ABSTRACT FROM AUTHOR]

The article discusses the transdermal testosterone therapy for the treatment of hypoactive sexual desire dysfunction (HSDD) in postmenopausal women. Topics discussed include circulating testosterone that is derived both from direct ovarian production, testosterone treatment that has shown to increase the number and frequency of satisfying sexual events, and clinicians to be ware of breast cancer.

Objective: This study aimed to document the prevalence and severity of vasomotor symptoms (VMS) and sexual symptoms among refugee women in Melbourne, Australia. Methods: This cross-sectional study included refugee women, aged 18–63 years, recruited from community centers and social media between February and July 2023. The Menopause-specific Quality of Life (MENQOL) questionnaire measured VMS and sexual symptoms. The scores were compared between different menopausal states. Results: Of 333 participants, 62.8% were premenopausal, 8.0% perimenopausal and 29.2% postmenopausal, with a median age of 40 years (range 18–63 years). Moderate–severe VMS was most prevalent amongst perimenopausal (20.8%; 95% confidence interval [CI]: 8.9–41.4%) versus postmenopausal (9.5%; 95% CI: 5.0–17.3%) and premenopausal (0%) women. Moderate–severe sexual symptoms affected 15.8% (95% CI: 5.2–39.3%) of perimenopausal and 16.9% (95% CI: 10.4–26.1%) of postmenopausal women versus 1.4% (95% CI: 0.3-5.3%) of premenopausal women. Perimenopausal and postmenopausal women had higher VMS and sexual symptom scores than premenopausal women (both p < 0.0001); the scores were also higher in perimenopausal women than postmenopausal women (p = 0.016 and p = 0.013, respectively). Conclusion: While perimenopausal and postmenopausal VMS and sexual symptoms are not uncommon amongst refugee women, these symptoms were less prevalent in postmenopausal refugees than in the non-refugee population. Further research is warranted to confirm and expand on these findings. [ABSTRACT FROM AUTHOR]

Testosterone has been studied for its benefits on sexual health for decades. The research regarding testosterone in women has produced evidence that this is a potential treatment for women suffering from female sexual dysfunction. There are several limitations of the testosterone trials that can affect their interpretation and challenges posed by some regulatory agencies that have prevented approval of any testosterone treatment for women in several countries. To summarize the challenges of testosterone trials in terms of study populations, patient-reported outcomes, validated instruments in research, confounders, and regulatory barriers. A thorough review of published data on testosterone for the treatment of women's sexual health problems was undertaken. A detailed evaluation of the limitations of these trials was conducted and incorporated with the published evidence on the regulatory processes involved in moving testosterone from clinical research to drug approval. Main outcome measures are assessment of clinical trial populations, survey tools, confounders, and regulatory barriers. There is some heterogeneity of study populations included in testosterone trials in women. Similarly, there have been differences in instruments used to assess patient-reported outcomes and often minimal control for potential confounders. The regulatory agency had posed a challenge to approve any testosterone treatment for women based on unproven concerns and a lack of regulatory guidance for drug developers. There is strong evidence that shows testosterone is effective for treating sexual health concerns in the women included in clinical trials. Strengths include thorough review of published literature and trial design for sexual health concerns. Limitations include being restricted to English Language publications and not having access to unpublished clinical trial data. Testosterone trials in women have been limited by homogeneity in the study populations and outcomes measured. Drug development has been hampered by inconsistent regulatory barriers. Rowen TS, Davis SR, Parish S, et al. Methodological Challenges in Studying Testosterone Therapies for Hypoactive Sexual Desire Disorder in Women. J Sex Med 2020;17:585–594. [ABSTRACT FROM AUTHOR]

In most countries, testosterone therapy is prescribed off-label such that women are using either testosterone formulations approved for men with dose modification, or compounded therapies. Current research into testosterone physiology and clinical effects should mainly focus on measuring total testosterone as the main biomarker rather than "free" testosterone, as evidence that "free" testosterone is the biologically active testosterone fraction is lacking[9] (Expert Opinion). Studies of non-oral testosterone therapies (percutaneous and injectable), I in doses that approximate physiological testosterone concentrations for premenopausal women i , have shown no significant adverse effects on lipid profiles over the short term (Level I, Grade A). Should a trial of testosterone therapy be given for HSDD, a baseline total testosterone concentration should be measured before commencement, with a repeat level 3-6 weeks after treatment initiation (Level IIA, Grade C). [Extracted from the article]

Menopause is a natural and universal experience for women between the ages of 45 and 55, marking a new phase in their lives. While menopause is not a disease, the biological changes that occur during this time can greatly impact a woman's quality of life and overall health. With more women living longer and experiencing menopause, it is important to prioritize women's health and well-being during this stage. The International Menopause Society (IMS) aims to promote and support access to best-practice healthcare for women during their menopause transition and post-reproductive years. The narrative surrounding menopause is highly individualized, and women should have personalized care options that are evidence-based and tailored to their needs. There are contrasting views on menopause in the media, which can leave women confused and disempowered. It is important to strike a balance in providing accurate information and empowering women to make informed decisions about their health. The IMS is committed to disseminating balanced, evidence-based information on menopause care to healthcare professionals and women worldwide. [Extracted from the article]

Summary: Background: We investigated whether metformin prevents tamoxifen‐induced endometrial changes and insulin resistance (IR) after a diagnosis of breast cancer. Methods: This was a single‐centre, randomized, double‐blind, placebo‐controlled, parallel group trial. Postmenopausal women with hormone receptor‐positive breast cancer taking tamoxifen were randomly allocated to metformin 850 mg or identical placebo, twice daily, for 52 weeks. Outcome measures included double endometrial thickness (ET) measured by transvaginal ultrasound, fasting insulin, glucose and IR estimated by the homeostasis model of assessment (HOMA‐IR). Results: A total of 112 women were screened and 102 randomized. Results are presented as median (range). The 101 women who took at least one dose of medication were aged 56 (43‐72) years, with 5(0.5‐28) years postmenopause, and had taken tamoxifen for 28.9 (0‐367.4) weeks. The baseline ET was 2.9 mm (1.4‐21.9) for the placebo group (n = 52) and 2.5 mm (1.3‐14.8) for the metformin group (n = 50). At 52 weeks, the median ET was statistically significantly lower for the metformin (n = 36) than for the placebo group (n = 45) (2.3 mm (1.4‐7.8) vs 3.0 (1.2‐11.3); P = 0.05). 13.3% allocated to placebo had an ET greater than 4 mm vs 5.7% for metformin (P = 0.26). There was no endometrial atypia or cancer. Compared with placebo, metformin resulted in significantly greater baseline‐adjusted reductions in weight (P < 0.001), waist circumference (0.03) and HOMA‐IR (P < 0.001). Conclusions: Metformin appears to inhibit tamoxifen‐induced endometrial changes and has favourable metabolic effects. Further research into the adjuvant use of metformin after breast cancer and to prevent EH and cancer is warranted. [ABSTRACT FROM AUTHOR]

A clinical practice audit was undertaken to share an Australian experience of the use of micronised progesterone ( mP) 100 mg daily as part of menopausal hormone therapy ( MHT). Ninety-nine women attending a single practitioner were offered the option of mP as a component of MHT, under the Australian Authorised Prescriber Scheme, over 2.5 years. Each of their files was independently audited. The mean age at commencement was 55.0 ( SD 6.6) years. Of the 93 postmenopausal women, 7 were lost to follow-up, 18 discontinued and treatment was ongoing for 68. The mean duration of treatment for those ongoing was 1.7 ( SD 0.5) years, and for those who discontinued, 0.6 ( SD 0.6) years. The most common side effect was unscheduled bleeding, which was also the most common reason for discontinuation (5/18 women). None of the 15 women who had a transvaginal ultrasound examination had an endometrial thickness >5 mm. Of the 41 women who had at least one blood progesterone measurement performed, the median value was 11.3 (range 0.7-138) nmol/L. This audit indicates that mP is well tolerated when prescribed as MHT. Although there was no evidence of endometrial hyperplasia, further research is needed to establish the safety of mP for continuous combined MHT use. [ABSTRACT FROM AUTHOR]

Introduction: Androgens have been implicated as important for female sexual function and dysfunction. Aim: To review the role of androgens in the physiology and pathophysiology of female sexual functioning and the evidence for efficacy of androgen therapy for female sexual dysfunction (FSD). Methods: We searched the literature using online databases for studies pertaining to androgens and female sexual function. Major reviews were included and their findings were summarized to avoid replicating their content. Main Outcome Measures: Quality of data published in the literature and recommendations were based on the GRADES system. Results: The literature supports an important role for androgens in female sexual function. There is no blood androgen level below which women can be classified as having androgen deficiency. Clinical trials have consistently demonstrated that transdermal testosterone (T) therapy improves sexual function and sexual satisfaction in women who have been assessed as having hypoactive sexual desire disorder. The use of T therapy is limited by the lack of approved formulations for women and long-term safety data. Most studies do not support the use of systemic dehydroepiandrosterone therapy for the treatment of FSD in women with normally functioning adrenals or adrenal insufficiency. Studies evaluating the efficacy and safety of vaginal testosterone and dehydroepiandrosterone for the treatment of vulvovaginal atrophy are ongoing. Conclusion: Available data support an important role of androgens in female sexual function and dysfunction and efficacy of transdermal T therapy for the treatment of some women with FSD. Approved T formulations for women are generally unavailable. In consequence, the prescribing of T mostly involves off-label use of T products formulated for men and individually compounded T formulations. Long-term studies to determine the safety of T therapy for women and possible benefits beyond that of sexual function are greatly needed. [ABSTRACT FROM AUTHOR]

The editorialists discuss recommendations from the Women's Preventive Services Initiative on screening for urinary incontinence in women and advise caution regarding widespread screening on the basis of limited, indirect evidence. [ABSTRACT FROM AUTHOR]

Topical alprostadil cream (Vitaros) is approved in Canada and Europe for the treatment of erectile dysfunction. To determine the effects on the female urogenital tract with repeated administration of the entire dose (300 μg alprostadil containing 2.5% dodecyl-2-n,n-dimethylaminopropionate hydrochloride), the vaginal pH, flora, and histology were assessed as a model for 100% transference from male to the female during unprotected sexual intercourse. Female cynomolgus monkeys were administered the entire dose of Vitaros for 14 days with a 7-day recovery. Relative to vehicle and placebo cream, the vaginal pH and microflora were determined at baseline and weekly, thereafter. Vaginal biopsies were evaluated at the end of dosing and recovery. All animals were clinically normal for the study duration, and the vaginal pH was consistent between dose groups and the dosing period. Vaginal microflora and histopathology findings of mild inflammation were generally similar across treatment groups. In conclusion, repeated vaginal exposure to Vitaros did not alter the pH, microflora, or histology after 14 daily doses, supporting the safety of Vitaros transference to the female partner. [ABSTRACT FROM PUBLISHER]

Purpose: This study compared the pharmacokinetics of a single dose of 1% testosterone solution after application to the inner arm or the axilla as application sites for transdermal testosterone therapy. Methods: Healthy, not pregnant, premenopausal women, 18 to 45 years of age with a body mass index of 20 to 28 kg/m² were enrolled into a single-center, open-label, randomized, 2-way crossover study. Serum total testosterone (TT), free testosterone (fT), and sex hormone binding globulin concentrations were measured. Pharmacokinetic parameters determined from serum TT and fT included area under the serum concentration versus time curve from time zero (predose) until 72 hours post-dose (AUC0-72), Cmax, and Tmax. Descriptive statistics were performed on serum concentrations of TT and fT for each site. ANOVA was performed on AUC0-72 and Cmax. Findings: A single-dose application of 1% testosterone solution to the inner arm and the axilla produced clear increases in TT and fT. Slower and lower increases in TT and fT were observed after treatment to the inner arm. Based on baseline-corrected AUC versus time curves, the bioavailability of 1% testosterone solution was increased 2-fold for the axilla compared with the inner arm. Implications: The absorption of a 1% testosterone solution was significantly greater after application to the axilla than to the inner arm. Study number DDS16; Australian Therapeutic Goods Administration, CTN 2005/158 [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to examine the effects of testosterone on verbal learning and memory in postmenopausal women. Design Randomized, placebo-controlled trial in which participants were randomized (1:1) to transdermal testosterone gel 300 mcg/day, or identical placebo, for 26 weeks. Patients Ninety-two postmenopausal women aged 55-65 years, on no systemic sex hormone therapy. Measurements The primary outcome was the score for the International Shopping List Task ( ISLT) of CogState. Secondary outcomes included other CogState domains, the Psychological General Well-Being Index ( PGWB) and safety variables. Results Eighty-nine women, median age 60 years, were included in the primary analysis. Testosterone treatment resulted in statistically significantly better performance for the ISLT (improved verbal learning and memory) compared with placebo, adjusted for age and baseline score (mean difference 1·57; 95% CI 0·13, 3·01) P = 0·03). There were no significant differences for other CogState domains or the PGWB scores. At 26 weeks, the median total testosterone was 1·7 n m (interquartile range ( IQR) 1·1, 2·4) in the testosterone group and 0·4 n m ( IQR 0·3, 0·5) in the placebo group. Conclusions The small but statistically significant effect of testosterone treatment on verbal learning and memory in postmenopausal women provides the basis for further clinical trials. [ABSTRACT FROM AUTHOR]

Highlights: [•] Brief review of normal androgen physiology in women. [•] Causes of low androgen levels in women. [•] Relationship between androgens and sexual function in women. [•] Current evidence for the use of testosterone therapy in women with sexual dysfunction. [•] Other effects of testosterone therapy. [•] Safety concerns. [•] Appropriate candidates for treatment. [ABSTRACT FROM AUTHOR]

Introduction It is a commonly held belief that combined oral contraceptive ( COC) pills containing an androgenic progestin may be less likely to impair sexual function than COCs containing an anti-androgenic progestin. Aim The study aims to compare the effects of a COC containing a progestin with an anti-androgenic profile (estradiol valerate [ E2V]/dienogest [ DNG]) to that of one with an androgenic progestin (ethinyl estradiol [ EE]/levonorgestrel [ LNG]) on sexual function in women with COC-associated sexual dysfunction. Methods In this multicenter, randomized, double-blind, noninferiority study, women with COC-associated female sexual dysfunction ( FSD) were randomized to E2V/DNG or EE/LNG for six cycles. The primary outcome was the change in the sum of Female Sexual Function Index ( FSFI) desire and arousal component scores between baseline and cycle 6. Secondary outcome measures included changes to the FSFI domains, the Female Sexual Distress Scale ( FSDS-R), Vaginal Health Assessment, the Atrophy Symptom Questionnaire, and the Psychological General Well Being Index over six treatment cycles. Main Outcome Measure The main outcome is the change in the sum of FSFI desire and arousal component scores between baseline and cycle 6. Results Of 276 women screened, 213 received treatment and 191 completed the study. The mean increase in the sum of FSFI desire and arousal component scores was 5.90 (standard deviation [ SD] 5.45) for E2V/DNG and 5.79 ( SD 6.17) for EE/LNG (change from baseline P < 0.0001, both groups). Both treatments showed equal efficacy and were associated with improvements in all domains of the FSFI, with no between-group differences. Both COCs reduced the distress associated with FSD, as indicated by reduced FSDS-R scores. Conclusion In women with COC-associated FSD, switching to either E2V/DNG or EE/LNG was associated with equivalent improvements in symptoms, challenging the perception that COCs containing anti-androgenic progestins have a detrimental effect on sexual function relative to those containing androgenic progestins. D avis SR , B itzer J , G iraldi A , P alacios S , P arke S , S errani M , M ellinger U , and N appi RE . Change to either a nonandrogenic or androgenic progestin-containing oral contraceptive preparation is associated with improved sexual function in women with oral contraceptive-associated sexual dysfunction. J S ex M ed 2013;10:3069-3079. [ABSTRACT FROM AUTHOR]

When I was invited to share my reflections on my Presidency of the International Menopause Society (IMS), I was initially uncertain as to how to approach this. Subsequently, the IMS has held its own successful World Congresses in Prague (2016) and Vancouver (2018) and, on reflection, management of the World Congress by the IMS has been a very positive step forward. In 2019, the IMS provided travel bursaries to support young people to attend each of these societies' congresses, and there was an IMS-supported symposium held at each congress, including an IMPART workshop at FLASCYM. [Extracted from the article]

This study evaluated the association of bladder cancer risk and fire scene investigation within a cohort of white male criminal investigators with the United States Bureau of Alcohol, Tobacco, Firearms and Explosives that was found to be at increased risk for bladder cancer. Medical surveillance data were used in a nested case-control study to determine odds ratios (ORs) estimating the relative risk of the cancer associated with post-fire investigation. The study comprised seven bladder cancer cases and 1525 controls. Six of the cases reported holding assignments associated with post-fire investigation. The OR for bladder cancer was 19.01 (95% confidence interval = 1.94-186.39) for those holding any one or more of these assignments for one to four years versus zero years and 12.56 (1.14-138.58) for those holding any one or more of these assignments for five or more years versus zero years. The risk for bladder cancer is significantly elevated for those holding post-fire investigation assignments compared to those not holding these assignments. [ABSTRACT FROM AUTHOR]

Objective Sex hormone-binding globulin (SHBG) is a robust predictor of insulin resistance. Whether this is independent of circulating sex steroid levels remains uncertain. The aim of this study was to investigate the determinants of SHBG in postmenopausal women and whether the relationship between SHBG and insulin resistance is independent of oestrogen and androgen levels. Design A cross-sectional study of naturally and surgically menopausal women. Participants Seven hundred and sixty three postmenopausal women not using any systemic hormone therapy, mean age 54·4 ± 5·8 years, recruited in the US, Canada, Australia, UK and Sweden between July 2004 and February 2005. Measurements Relationships between log-transformed (ln) SHBG and ln homoeostasis model assessment for insulin resistance (HOMA-IR) were explored, taking into account age, body mass index (BMI), blood pressure (BP) and circulating oestradiol, oestrone, testosterone and dihydrotestosterone. Results Taking into account age, race, years since menopause, menopause type, BMI, BP, prior postmenopausal hormone use and the sex steroids measured, 34·4% of the variation in SHBG could be explained by the model that included negative contributions by HOMA-IR, BMI and diastolic BP, and a positive contribution by total testosterone ( P < 0·001). None of the sex steroids made independent contributions to HOMA-IR, which was best explained by the model that included BMI, SHBG, systolic BP and surgical menopause, with each variable being positively related to HOMA-IR ( r2 = 0·3152, P = 0·03). Conclusions The relationship between SHBG and HOMA-IR, as an estimate of insulin resistance, is not explained by endogenous oestrogen and androgen levels and is, at least in part, independent of BMI in postmenopausal women. [ABSTRACT FROM AUTHOR]

Abstract: In recent years the perimenopause has become recognised as a ‘window of vulnerability’ for women''s mood. The risk of depression during perimenopause is high and treatment failure is common. Perimenopausal depression encompasses both new onset (first episode) depression occurring during perimenopause as well as a relapse during perimenopause in women with a history of depression. Perimenopausal depression is increasingly recognised as a new subtype of depression with specific clinical characteristics. Current treatments for perimenopausal depression have high failure rates, multiple adverse effects and potentially damaging long term consequences. This review examines both new onset and relapsed depression during perimenopause, biological mechanisms of perimenopausal depression, and the role of hormonal therapies. [Copyright &y& Elsevier]

Donepezil hydrochloride is a reversible acetyl cholinesterase inhibitor approved for Alzheimer disease treatment. As an alternate therapy, a donepezil hydrochloride transdermal patch is in development. Recommended nonclinical safety studies include a 3-month Good Laboratory Practice (GLP) dose-range finding (DRF) study prior to conducting the 2-year dermal carcinogenicity study in rats. Demonstration of systemic exposure is necessary to interpret the in vivo data. Previous nonclinical reports supporting oral dosing have utilized liquid chromatography tandem mass spectrometry (LC/MS/MS) to quantify donepezil concentrations in plasma. Smaller species with limited blood volumes do not allow serial sampling to derive the full pharmacokinetic profile from a single animal. Therefore, the option of another analytical method requiring decreased sample volumes is desirable as it would decrease the required number of animals while obtaining the complete profile. The dried blood spot (DBS) technique allows drug level measurement from a few microliters; however, the method is still not widely utilized in GLP studies. Because donepezil plasma levels are known by the oral route, DBS was used to bridge the previous oral data and to support a 13-week GLP DRF study for repeated topical application in rats, comparing oral administration with 4 topical formulations. The DBS method was validated and demonstrated robustness and reproducibility for application to the DRF study. The assay results were comparable to a previously reported plasma LC/MS/MS assay-derived pharmacokinetic profile and provided justification for selection of the topical formulation and dose levels for the subsequent dermal carcinogenicity study. [ABSTRACT FROM AUTHOR]

Objective: To explore the beliefs held by breast cancer (BC) survivors about the factors that contribute to the development of their BC. Methods: The BUPA Health Foundation Health and Well-being after Breast Cancer Study is a prospective cohort study of 1684 women recruited within 12 months of their first diagnosis with invasive BC. Participants completed an enrollment questionnaire (EQ), first follow-up questionnaire (FQ1) and a second follow-up questionnaire (FQ2), 12 months and 24 months post-EQ, respectively. In the FQ2, women were asked whether they believed anything contributed to the development of their BC and whether they had made lifestyle changes since the FQ1. Well-being was assessed at the FQ2 using the Psychological General Well-being Index (PGWB). Results: In total, 1496/1684 women completed the FQ2 and 43.5% reported belief in a factor that may have contributed to their developing BC. These women were more likely to be younger ( p<0.0001) and educated beyond high school ( p<0.0001). Stress (58.1%) was the most common reason given, followed by previous use of hormone therapy (17.0%) and a family history of any cancer (9.8%). Women who believed stress contributed to their BC had lower PGWB scores than other study participants (70.9 ± 16.1, n = 361 versus 77.3 ± 14.9, n = 1071, mean difference = 6.4, 95% CI: 4.6-8.2 p<0.0001) and were more likely to have made lifestyle changes since their BC diagnosis. Conclusions: Many women with BC believe that stress has contributed to their condition. Women who held this belief were more likely to adopt strategies to reduce stress than those who did not. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction. Hypoactive sexual desire disorder (HSDD) is a common problem in postmenopausal women, but in the absence of an approved medical treatment in the United States, off-label testosterone use is widespread. Large, randomized controlled studies have demonstrated that transdermal testosterone improves sexual function and activity in postmenopausal women and has favorable short-term safety. However, a longer-term safety profile of testosterone must be established before a testosterone product for women is approved. Aim. To review current knowledge of the efficacy and safety of transdermal testosterone based on presentations at a satellite symposium during the 2011 annual meeting of the International Society for the Study of Women's Sexual Health. Methods. Pertinent information included in the presentations was augmented with relevant articles from the peer-reviewed literature. Main Outcome Measures. The rationale for testosterone therapy and results from phase III and other clinical studies with the testosterone patch in postmenopausal women with HSDD and findings from studies investigating the cardiovascular, breast, and endometrial effects of testosterone therapy. Results. Randomized, double-blind, placebo-controlled studies have established the efficacy of the transdermal testosterone patch for relieving symptoms of HSDD in surgically and naturally menopausal women with and without concomitant estrogen or estrogen/progestin therapy. The main side effects reported in clinical trials were increased hair growth and acne. Available safety data for testosterone, although not conclusive, were reassuring with respect to cardiovascular, breast, and endometrial outcomes. Interim data from a long-term phase III safety trial of a testosterone gel demonstrate a continued low rate of cardiovascular events and breast cancer in postmenopausal women at increased cardiovascular risk. Conclusion. Transdermal testosterone appears to be an effective and safe therapy for postmenopausal women with HSDD. Davis SR and Braunstein GD. Efficacy and safety of testosterone in the management of hypoactive sexual desire disorder in postmenopausal women. J Sex Med 12;9:1134-1148. [ABSTRACT FROM AUTHOR]

This study investigated a bladder cancer cluster in a cohort of employees, predominately criminal investigators, participating in a medical surveillance program with the United States Bureau of Alcohol, Tobacco, Firearms and Explosives (ATF) between 1995 and 2007. Standardized incidence ratios (SIRs) were used to compare cancer incidences in the ATF population and the US reference population. Seven cases of bladder cancer (five cases verified by pathology report at time of analysis) were identified among a total employee population of 3,768 individuals. All cases were white males and criminal investigators. Six of seven cases were in the 30 to 49 age range at the time of diagnosis. The SIRs for white male criminal investigators undergoing examinations were 7.63 (95% confidence interval = 3.70-15.75) for reported cases and 5.45 (2.33-12.76) for verified cases. White male criminal investigators in the ATF population are at statistically significant increased risk for bladder cancer. [ABSTRACT FROM AUTHOR]

Abstract: Vaginal atrophy is a common symptom of postmenopausal estrogen deficiency and can present as dryness, irritation, infection and dyspareunia and can affect sexual function and quality of life. Currently vaginal atrophy is treated with the intravaginal application of preparations containing estradiol or estriol, which are both effective and safe. It has been proposed that intravaginally administered dehydroepiandrosterone (DHEA) can be used to treat vaginal atrophy. DHEA and its sulphate DHEAS are the most abundant circulating sex steroid hormones in women, and provide a large precursor reservoir for the intracellular production of androgens and estrogens in non-reproductive tissues. Levels of DHEA and DHEAS decline with age. Although there is some evidence to support the use of intravaginal DHEA for postmenopausal women with symptoms of vaginal atrophy, independent studies are required to confirm this. In addition studies regarding the effects of vaginal DHEA on sexual function in women without vaginal atrophy are needed. Given that the efficacy and long term safety of low dose vaginal estradiol and estriol therapy is well established and that vaginal estrogen requires application of 2–3 times a week, rather than daily dosing; the benefit of daily vaginal DHEA over estrogen also needs to be considered as women may find it unpalatable to adhere to daily dosing with a cream preparation. [Copyright &y& Elsevier]

Background: The efficacy and safety of testosterone treatment for hypoactive sexual desire disorder in postmenopausal women not receiving estrogen therapy are unknown. Methods: We conducted a double-blind, placebo-controlled, 52-week trial in which 814 women with hypoactive sexual desire disorder were randomly assigned to receive a patch delivering 150 or 300 µg of testosterone per day or placebo. Efficacy was measured to week 24; safety was evaluated over a period of 52 weeks, with a subgroup of participants followed for an additional year. The primary end point was the change from baseline to week 24 in the 4-week frequency of satisfying sexual episodes. Results: At 24 weeks, the increase in the 4-week frequency of satisfying sexual episodes was significantly greater in the group receiving 300 µg of testosterone per day than in the placebo group (an increase of 2.1 episodes vs 0.7, p < 0.001) but not in the group receiving 150 µg per day (1.2 episodes, p = 0.11). As compared with placebo, both doses of testosterone were associated with significant increases in desire (300 µg per day, p < 0.001; 150 µg per day, p = 0.04) and decreases in distress (300 µg per day, p < 0.001; 150 µg per day, p = 0.04). The rate of androgenic adverse events --primarily unwanted hair growth-- was higher in the group receiving 300 µg of testosterone per day than in the placebo group (30.0% vs23.1%). Breast cancer was diagnosed in four women who received testosterone (as compared with none who received placebo); one of the four received the diagnosis in the first 4 months of the study period, and one, in retrospect, had symptoms before undergoing randomization. Conclusions: In postmenopausal women not receiving estrogen therapy, treatment with a patch delivering 300 µg of testosterone per day resulted in a modest but meaningful improvement in sexual function. The long-term effects of testosterone, including effects on the breast, remain uncertain. [ABSTRACT FROM AUTHOR]

Abstract: In women, sexual function, hormones and aging are inextricably related. Sexual activity in women involves interest and motivation, the ability to become aroused and achieve orgasm, the pleasure of the experience and subsequent personal satisfaction. Androgens, as endogenous hormones or given as a therapy, potentially influence female sexual function, with research into the effects of exogenous androgens in women mostly devoted to effects on sexual desire. Some studies have been conducted to delineate the effects of testosterone on arousal, however arousal determined by laboratory measures does not always correlate with subjective reporting of a sensation of arousal. Overall large randomised controlled trials of exogenous testosterone show benefits over placebo on sexual desire, arousal, orgasm, pleasure and satisfaction. The aspects of consideration of androgen therapy for women that continue to stimulate debate in this therapeutic area include whether female sexual dysfunction is a condition that merits pharmacotherapy, how effective is such treatment and whether testosterone therapy is safe. [Copyright &y& Elsevier]

Abstract: Background: Dehydroepiandrosterone (DHEA) and its sulphate DHEAS are the most abundant sex steroids in women and provide a large reservoir of precursors for the intracellular production of androgens and estrogens in non-reproductive tissues. Levels of DHEA and DHEAS decline with age. It has been proposed that restoring the circulating levels of these steroids to those found in young women may have anti-aging effects and improve sexual function and wellbeing in postmenopausal women. Aim: To review the published literature for the efficacy of DHEA therapy data regarding safety. Methods: A systematic literature search of MEDLINE (Ovid) and Pub-Med (1966 to November 2009) for original studies that included any of the terms dehydroepiandrosterone, DHEA or DHEAS, sexual function, wellbeing, women and metabolic parameters of interest. Results: Overall the interpretation of the data was limited by inadequate sample size and short treatment duration of available studies with inconsistent results. The more recent randomized controlled trials however do not support a benefit of oral DHEA therapy for women. A possible benefit that emerged is that vaginally administered DHEA may improve vaginal atrophy with concomitant improvements in sexual function in women who are estrogen deficient due to menopause. The potential value of oral DHEA therapy for postmenopausal women is called into question. [Copyright &y& Elsevier]

The available clinical evidence supports efficacy of testosterone therapy for the treatment of postmenopausal women with hypoactive sexual desire disorder (HSDD) who have undergone a comprehensive clinical evaluation. Although few preparations designed to deliver an appropriate dose of testosterone for women are available, use of testosterone by women for the management of HSDD is widespread. Issues that continue to simulate debate in this therapeutic area include whether HSDD is a condition that merits pharmacotherapy, how effective is such treatment and whether testosterone therapy is safe. Hence the question, should women receive androgen replacement therapy, and if so, how? [ABSTRACT FROM AUTHOR]

Introduction. Although the efficacy of testosterone for the treatment of hypoactive sexual desire disorder is well established, the effect of testosterone therapy on breast cancer risk remains uncertain. Aim. The incidence of invasive breast cancer among past and current testosterone users. Methods. Retrospective cohort study of 631 women ever treated with testosterone between January 1989 and December 2007 in a clinical endocrinology practice. Main Outcome Measure. The incidence of invasive breast cancer since first exposure, and the standardized incidence rate ratio (IRR) calculated using Australian age-specific incidence rates for 2005. Results. The mean age of the women at first exposure to testosterone therapy was 49.1 ± 8.2 years, median treatment duration, 1.3 years, and mean follow-up of 6.7 ± 4.6 years, providing 4,015 woman-years of follow-up. Twelve cases of invasive breast cancer occurred among 599 women breast cancer-free before treatment, giving an age adjusted IRR of 1.35 (95% confidence interval 0.76–2.38). There was no evidence of an independent effect of duration of exposure on breast cancer risk. Conclusion. In this study, testosterone use was not associated with a significant increase in breast cancer risk. Davis SR, Wolfe R, Farrugia H, Ferdinand A, and Bell RJ. The incidence of invasive breast cancer among women prescribed testosterone for low libido. J Sex Med 2009;6:1850–1856. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The aim of this study was to document the age-specific prevalence of different types of urinary incontinence (UI) in women and to identify the risk factors associated with each type of UI. Design: A detailed self-administered questionnaire was mailed to 542 community-dwelling women, aged 24–80 years. The questionnaire included a validated instrument, the Questionnaire for Urinary Incontinence Diagnosis (QUID), for the assessment of stress, urge and mixed UI. Results: Five hundred and six of the 542 women provided data (93.4%). The overall prevalence of any UI was 41.7% [95% confidence interval (CI): 37.2–45.8%]. Of the 210 women reporting UI, 16% [95% CI: 12.9–19.3%] reported stress only; 7.5% [95% CI: 5.2–9.8%] reported urge only and 18% [95% CI: 14.7–21.5%] reported a mixed pattern. Stress incontinence was most common amongst middle-aged women (25.3% of women aged 35–44 years), while urge incontinence was most common in women over the age of 75 years (24.2%). In logistic regression analyses, obesity (p <0.001) and being parous (p =0.019) were found to be significantly associated with stress incontinence, increasing age (p =0.002) with urge incontinence, and being overweight (p =0.035) or obese (p <0.001) and having had a hysterectomy (p =0.021) with mixed incontinence. Conclusions: UI is a highly prevalent condition in women living in the community. Stress, urge and mixed incontinence have different age distributions and risk factors. These data are important in understanding the etiology, management and possible prevention of these conditions. [Copyright &y& Elsevier]

The article presents a double-blind, placebo-controlled trial which tested the efficacy of testosterone treatment for hypoactive sexual desire disorder in postmenopausal women. 814 women were randomly assigned to receive a testosterone patch delivering 150µg or 300µg of testosterone per day or placebo. The study measured efficacy to week 24 and evaluated safety over a 52 week period. The number of satisfying sexual episodes was found to be significantly greater in the group receiving 300µg than in the placebo group. The number was not significantly greater in the group receiving 150 µg per day. The rate of androgenic adverse events was greater for those receiving 300µg. Researchers note that the long-term effects of testosterone remain uncertain.

Hypopituitarism is a rare disorder, but its prevalence has increased as a result of an increase in secondary causes of hypopituitarism such as traumatic brain injury and cranial irradiation. Estrogen with or without progestogen (progestin) treatment is conventional therapy in women with hypopituitarism. Recent data demonstrate that women with hypopituitarism may experience marked androgen deficiency as a consequence of secondary loss of function of the adrenal cortex and/or ovaries. This deficiency is not always considered and therefore androgen therapy is not routinely prescribed. Recent clinical trials indicate that testosterone supplementation in physiological doses for androgen-deficient women with hypopituitarism may improve psychological well-being and sexual function, and increase bone mineral density and lean body mass. Dehydroepiandrosterone (DHEA; prasterone) supplementation may be an option for women with hypopituitarism who have secondary adrenal insufficiency and low levels of DHEA and DHEA sulfate. While short-term treatment with testosterone or DHEA appears to be safe, long-term safety data are lacking. Androgenic adverse effects limit the acceptability of treatment for some women. Further studies to establish the efficacy and safety of androgen treatment for long-term intervention in a larger group of hypopituitary androgen-deficient women are needed. [ABSTRACT FROM AUTHOR]

The investigation of female sexual dysfunction (FSD) is an evolving area in which definitions and models for female sexual functioning are being continually reviewed and revised. The lack of consensus amongst experts in the field and regulating authorities regarding appropriate inclusion and exclusion criteria for FSD trials, and main outcome measures appropriate for the evaluation of drug interventions has somewhat hampered progression in this area. Nonetheless, there is evidence from randomized controlled trials that androgen therapy improves the quality of the sexual experience for postmenopausal women with low libido, and preliminary data that this may also apply to premenopausal women. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) mortality is declining such that the number of survivors of BC in the community is increasing. BC survivors report a range of sequelae from their cancer and its management beyond the period of their immediate treatment. Previous studies to document these have generally been small, clinic-based or commenced years after diagnosis. We have recruited a large cohort of women newly diagnosed with invasive BC from the community who will be followed for five years in order to systematically document the physical, psychological and socio-economic consequences of BC and its treatment. The aim of this manuscript is to describe the issues encountered in the recruitment of this community-based study population. Methods: Women residing in the southern Australian state of Victoria newly diagnosed with invasive BC were recruited to this cohort study using two approaches: directly from the community using an advertising campaign and contemporaneously using an invitation to participate from the Victorian Cancer Registry (VCR). Results: Over the two and half year recruitment period, 2135 women were recruited and agreed to receive the enrollment questionnaire (EQ). Of these, 1684 women were eligible and completed an EQ, with the majority of participants having been recruited through the VCR (n = 1321). Only 16% of women contacted by the VCR actively refused participation following a letter of invitation and phone follow-up. The age distribution and tumour characteristics of participants are consistent with state-wide data and their residential postcodes include 400 of a possible 699. Recruitment through a direct community awareness program aimed at women with newly diagnosed invasive BC was difficult, labour-intensive and expensive. Barriers to the recruitment process were identified. Conclusion: Most of the women in this study were recruited through a state-based cancer registry. Limitations to recruitment occurred because we required questionnaires to be completed within 12 months of diagnosis in a setting where there is several months delay in notification of new cases to the Registry. Characteristics of the cohort suggest that it is generally representative of women in the state of Victoria newly diagnosed with BC. [ABSTRACT FROM AUTHOR]

Abstract: To date there is no clinical indication for the use of testosterone in women and long-term safety data is lacking. This minireview examines androgen therapy in women. Issues relating to research into sexual function and androgens in women are discussed. Androgen physiology is described and studies examining endogenous androgens in women cited. A Cochrane review found that adding testosterone to a hormone therapy regimen has beneficial effects on sexual function in postmenopausal women and subsequent studies have supported the role of testosterone in sexual function and well-being. However studies on safety and efficacy of testosterone beyond 24 weeks are lacking. [Copyright &y& Elsevier]

During the past few years, many women and doctors have revised their opinions of hormone replacement therapy (HRT) for menopausal symptoms, and a substantial number of individuals have discontinued its use because of concerns about side-effects. Numerous alternatives to HRT are promoted, and assessment of the quality of evidence about the safety and effectiveness of these compounds can be difficult. In this Review, we summarise the data from studies addressing the efficacy, risks, and benefits of frequently prescribed treatments, and offer evidence-based clinical guidelines for the management of menopausal symptoms. Although few comparative studies exist, oestrogen alone or combinations of oestrogen and progestagen are likely to be the most effective treatments for menopausal hot flushes and vaginal dryness. Tibolone is as effective as HRT, however, and might also improve libido. For those who wish to avoid hormonal treatments, there are few effective options. Selective serotonin reuptake inhibitors might be effective in the very short term (less than 12 weeks) and are well tolerated. There is not enough evidence that any of the complementary therapies available are any better than placebo for menopausal vasomotor symptoms, and few safety data exist. [ABSTRACT FROM AUTHOR]

Context It has been proposed that low sexual desire and sexual dysfunction are associated with low blood testosterone levels in women. However, evidence to support this is lacking. Objective To determine whether women with low self-reported sexual desire and sexual satisfaction are more likely to have low serum androgen levels than women without self-reported low sexual desire and sexual satisfaction. Design, Setting, and Participants A community-based, cross-sectional study of 1423 women aged 18 to 75 years, who were randomly recruited via the electoral roll in Victoria, Australia, from April 2002 to August 2003. Women were excluded from the analysis if they took psychiatric medication, had abnormal thyroid function, documented polycystic ovarian syndrome, or were younger than 45 years and using oral contraception. Main Outcome Measures Domain scores of the Profile of Female Sexual Function (PFSF) and serum levels of total and free testosterone, androstenedione, and dehydroepiandrosterone sulfate. Results A total of 1021 individuals were included in the final analysis. No clinically significant relationships between having a low score for any PFSF domain and having a low serum total or free testosterone or androstenedione level was demonstrated. A low domain score for sexual responsiveness for women aged 45 years or older was associated with higher odds of having a serum dehydroepiandrosterone sulfate level below the 10th percentile for this age group (odds ratio [OR], 3.90; 95% confidence interval [CI], 1.54-9.81; P = .004). For women aged 18 to 44 years, having a low domain score for sexual desire (OR, 3.86; 95% CI, 1.27-11.67; P = .02), sexual arousal (OR, 6.39; 95% CI, 2.30-17.73; P<.001), and sexual responsiveness (OR, 6.59; 95% CI, 2.37-18.34; P<.001) was associated with having a dehydroepiandrosterone sulfate level below the 10th percentile. Conclusions No single androgen level is predictive of low female sexual function, and the majority of women with low dehydroepiandrosterone sulfate levels did not have low sexual function. [ABSTRACT FROM AUTHOR]

Abstract: Objectives:: To compare the efficacy and patient acceptability of intranasal and transdermal 17β-oestradiol delivery systems for postmenopausal symptoms in Australasian women. Methods:: Symptomatic postmenopausal women were randomly assigned to treatment with either intranasal 17β-oestradiol, 300μg daily (n = 66) or transdermal matrix patch 17β-oestradiol, 50μg/day (n = 66) for 12 weeks, followed by a 4-week period with the alternate treatment. Efficacy was compared between groups using the modified Greene climacteric scale, the menopause quality of life (MENQOL) questionnaire and vasomotor symptoms at week 12. Patient acceptability was compared by a satisfaction questionnaire at week 16 and patient preference at week 16. Results:: Intranasal and transdermal therapy produced significant reductions in both the Modified Greene and MENQOL scores, and in the occurrence of hot flushes and night sweats at week 12. The overall rate of reported vasomotor symptoms was lower on patients treated with the nasal spray. Both therapies were well tolerated with similar adverse event rates. Satisfaction and preference were similar for both modes of drug delivery. Conclusions:: Intranasal oestradiol therapy route has comparable efficacy and safety to that of transdermal oestradiol matrix patch therapy with no difference in patient preference or satisfaction. [Copyright &y& Elsevier]

Background: Testosterone therapy is being increasingly used in the management of postmenopausal women. However, as clinical trials have demonstrated a significantly increased risk of breast cancer with oral combined estrogen–progestin therapy, there is a need to ascertain the risk of including testosterone in such regimens. Objective: Evaluation of experimental and epidemiological studies pertaining to the role of testosterone in breast cancer. Design: Literature review. Setting: The Jean Hailes Foundation, Research Unit. Main Outcome Measures: Mammary epithelial proliferation, apoptosis and breast cancer. Results: In experimental studies, testosterone action is anti-proliferative and pro-apoptotic, and mediated via the AR, despite the potential for testosterone to be aromatized to estrogen. Animal studies suggest that testosterone may serve as a natural, endogenous protector of the breast and limit mitogenic and cancer promoting effects of estrogen on mammary epithelium. In premenopausal women, elevated testosterone is not associated with greater breast cancer risk. The risk of breast cancer is also not increased in women with polycystic ovary syndrome who have chronic estrogen exposure and androgen excess. However, in postmenopausal women, who are oestrogen deplete and have increased adipose aromatase activity, higher testosterone has been associated with greater breast cancer risk. Conclusion: Available data indicate the inclusion of testosterone in estrogen–progestin regimens has the potential to ameliorate the stimulating effects of hormones on the breast. However, testosterone therapy alone cannot be recommended for estrogen deplete women because of the potential risk of enhanced aromatisation to estrogen in this setting. [Copyright &y& Elsevier]

Introduction. Various endogenous hormones, including estrogen, testosterone, progesterone and prolactin, may influence female sexual function. Aim. To provide recommendations for the diagnosis and treatment of women with endocrinologic sexual difficulties. Methods. The Endocrine Aspects of Female Sexual Dysfunction Committee was part of a multidisciplinary International Consultation. It included four experts from two countries and several peer reviewers. Main Outcome Measure. Expert opinion was based on committee discussion, a comprehensive literature review and evidence-based grading of available publications. Results. The impact of hormones on female sexual function and their etiological roles in dysfunction is complex. Research data are limited as studies have been hampered by lack of precise hormonal assays and validated measures of sexual function in women. Sex steroid insufficiency is associated with urogenital atrophy and may also adversely affect central sexual thought processes. Systemic estrogen/estrogen progestin therapy alleviates climacteric symptoms but there is no evidence that this therapy specifically improves hypoactive sexual desire disorder (HSDD) in premenopausal or postmenopausal women. Exogenous testosterone has been shown in small randomized controlled trials (RCT) to improve sexual desire, arousal and sexual satisfaction in both premenopausal and postmenopausal women. However, as there is no biochemical measure that clearly identifies who to treat, use of exogenous testosterone should be considered only after other causes of HSDD have been excluded, such as depression, relationship problems and ill health. The clinical assessment of HSDD should include detailed medical, gynecologic, sexual and psychosocial history and physical examination including the external/internal genitalia. Hormonal therapy should be individualized and risks/benefits fully discussed, and all treated women should be carefully followed up and monitored for therapeutic side effects. Conclusions. There is a need for prospective, multi-institutional clinical trials to define safe and effective endocrine treatments for female sexual dysfunction. [ABSTRACT FROM AUTHOR]

Abstract The use of postmenopausal hormone therapy (HT) has recently generated much debate following the results of various large randomised controlled trials. This has challenged physicians to reassess the use of HT in each individual woman within the realm of her symptomatology and risk profile for long-term illnesses. There are several areas of definite benefit or risk and many areas of uncertainty. The results of recent randomised controlled trials pertain to the specific HT regimens used and the characteristics of the study groups, such that the conclusions cannot be extrapolated to the use of HT in general. (Intern Med J 2004; 34: 109−114) [ABSTRACT FROM AUTHOR]

The role of androgen treatment in women remains controversial. The proposed “Female Androgen Insufficiency Syndrome” (Fertility and Sterility, April 2002) describes a number of non-specific symptoms including unexplained fatigue, decreased well being/dysphoric mood and/or blunted motivation and diminished sexual function. An estimated 40% of women experience sexual dysfunction, highlighting the need for ongoing research into this field in order to fully define the possible contribution of androgen insufficiency. The increasing availability of products, such as dehydroepiandrosterone (DHEA) supplements also points to the need for controlled studies to assess the safety of these and other preparations.Measurement of androgens in women requires sensitive assays with the ability to detect low levels and a narrow range with precision. Normal ranges of androgens for women of reproductive and post-reproductive age remain poorly defined. Debate exists as per importance of measurement of free versus total testosterone, with the ‘free androgen index’ offering an alternative method of assessment of testosterone availability.Testosterone treatment is being developed for women in the form of transdermal patches, gels or cream, with percutaneous implants in common usage in some countries. Recent research has highlighted alternative means of administration, such as oral inhalation or buccal lozenge. DHEA is widely available in some countries. Research to date has demonstrated improvements in libido and sexual function, mood and well being. Evidence points to other potential benefits of androgen treatment, including preservation of bone mass, a possible protective role in breast cancer and beneficial effects on cognition.Adverse effects of androgen treatment in women are dose-dependent and include virilisation, mood disturbance and acne. These are uncommon if appropriate doses are administered and highlight the need for treatment to be closely monitored clinically and biochemically. Beneficial effects of testosterone treatment in post-menopausal women with lowered androgen levels have been well documented, and preliminary evidence suggests a role for treatment in pre-menopausal women with symptoms and lowered testosterone levels. [Copyright &y& Elsevier]

To date, no formal definition of female androgen insufficiency (FAI) based on strong epidemiological data exists. However the proposed key symptoms of FAI, being reduced libido, diminished well-being, and lowered mood, have been reported to respond well to testosterone replacement, generally without significant adverse effects. Androgens are quantitatively the predominant sex steroid in women, circulating in the micro- and nanomolar concentration range, compared with picomolar levels of estrogens. Androgens have important physiological roles in women, acting both as precursors for estrogen biosynthesis and directly via the androgen receptor. The most significant biologically active androgen is testosterone, which circulates bound tightly to sex hormone binding globulin and loosely to albumin. Circulating androgen levels decline in the years preceding menopause. This may be attributed to the gradual reduction in adrenal androgen production with age and to the loss of cyclical ovarian androgen production in the late reproductive years. Those who experience surgical menopause, have adrenal insufficiency or pituitary insufficiency, or those who experience premature ovarian failure, also have reduced androgen production. Androgen replacement therapy in the form of either dehydroepiandrosterone or testosterone is becoming increasingly widespread for the treatment of FAI. Evidence exists for the benefits of such therapy in relieving both the physical and psychological symptoms thought to be due to FAI in clinically affected women. However, clear guidelines regarding the diagnosis of androgen insufficiency, optimal therapeutic doses, and long-term safety remain lacking. [ABSTRACT FROM AUTHOR]

Summary Postmenopausal hormonal therapy is used to manage the climacteric symptoms that impair the quality of life of a substantial number of women. The difficulty is achieving the desired effects with minimal side-effects and no adverse health risks. Fundamental to this is understanding the physiology of oestrogen in women and the metabolism of the therapeutic compounds. Although the effects of oral oestrogen therapy have been studied extensively, there is insufficient evidence to assess adequately the independent effects of progestin use, other oestrogen compounds, differing doses and duration of treatment. We have reviewed some basic concepts of oestrogen physiology and how these relate to exogenous oestrogen administration, the risks of greatest concern, and the role of androgens and newer treatment alternatives. [ABSTRACT FROM AUTHOR]

Objective: To review causes of female androgen insufficiency (FAI) other than menopause. Design: A review of the available literature in this field. Result(s): Androgen levels decline with increasing age during the reproductive years in healthy women and vary little or not at all across menopause, with controversy as to whether levels change in the postmenopausal years. Thus the premenopausal decline in androgens potentially is the most common cause of female androgen insufficiency (FAI), whereas natural menopause in itself is not a cause of androgen deficiency. Pathophysiological causes of FAI can be divided into those that affect ovarian androgen production, those that affect adrenal androgen production, and combined deficiency states. Surgical menopause is characterized by an abrupt onset of symptoms, in contrast to a more insidious onset of relatively nonspecific symptoms in women who have FAI due to aging. Conclusion(s): The decline in testosterone with normal aging before menopause may well be the most common cause of FAI, although many women do not present with symptoms and most are not diagnosed until they have reached menopause. [ABSTRACT FROM AUTHOR]

Objective: To review causes of female androgen insufficiency (FAI) other than menopause.Design: A review of the available literature in this field.Result(s): Androgen levels decline with increasing age during the reproductive years in healthy women and vary little or not at all across menopause, with controversy as to whether levels change in the postmenopausal years. Thus the premenopausal decline in androgens potentially is the most common cause of female androgen insufficiency (FAI), whereas natural menopause in itself is not a cause of androgen deficiency. Pathophysiological causes of FAI can be divided into those that affect ovarian androgen production, those that affect adrenal androgen production, and combined deficiency states. Surgical menopause is characterized by an abrupt onset of symptoms, in contrast to a more insidious onset of relatively nonspecific symptoms in women who have FAI due to aging.Conclusion(s): The decline in testosterone with normal aging before menopause may well be the most common cause of FAI, although many women do not present with symptoms and most are not diagnosed until they have reached menopause. [ABSTRACT FROM AUTHOR]