Obesity and sexual health: focus on postmenopausal women.

Menopause is a cardiometabolic transition with many women experiencing weight gain and redistribution of body fat. Hormonal changes may affect also several dimensions of well-being, including sexual function, with a high rate of female sexual dysfunction (FSD), which displays a multifactorial etiology. The most important biological factors range from chronic low-grade inflammation, associated with hypertrophic adipocytes that may translate into endothelial dysfunction and compromised blood flow through the genitourinary system, to insulin resistance and other neuroendocrine mechanisms targeting the sexual response. Psychosocial factors include poor body image, mood disorders, low self-esteem and life satisfaction, as well as partner's health and quality of relationship, and social stigma. Even unhealthy lifestyle, chronic conditions and putative weight-promoting medications may play a role. The aim of the present narrative review is to update and summarize the state of the art on the link between obesity and FSD in postmenopausal women, pointing to the paucity of high-quality studies and the need for further research with validated end points to assess both biomarkers of obesity and FSD. In addition, we provide general information on the diagnosis and treatment of FSD at menopause with a focus on dietary interventions, physical activity, anti-obesity drugs and bariatric surgery.

Different local estrogen therapies for a tailored approach to GSM.

Local estrogen therapy (LET) is the mainstay of treatment for vaginal dryness, dyspareunia and other urogenital symptoms because it may reverse some pathophysiological mechanisms associated with decreasing endocrine function and increasing aging. Over the years, several vaginal products including different formulations (tablets, rings, capsules, pessaries, creams, gels and ovules) and molecules (estradiol [E2], estriol [E3], promestriene, conjugated equine estrogens and estrone) have been used with superimposable therapeutic results. Low-dose and ultra-low-dose LET is the gold standard due to its minimal systemic absorption, with circulating E2 levels persistently remaining in the postmenopausal range. In healthy postmenopausal women, preference among the various products is presently the main driver and dissatisfaction with LET seems high, namely because of the delayed use in those with severe symptoms of genitourinary syndrome of menopause (GSM). Specific concerns remain in high-risk populations such as breast cancer survivors (BCS), especially those under treatment with aromatase inhibitors. Based on the multitude of symptoms under the umbrella of GSM definition, which includes vulvovaginal atrophy (VVA), it is mandatory to investigate specific effects of LET on quality of life, sexual function and genitourinary conditions by conducting studies with a patient-tailored focus.

Expert opinion on the treatment of vulvovaginal atrophy with ospemifene based on new evidence.

Vulvovaginal atrophy (VVA) is an underdiagnosed and undertreated chronic condition resulting in physiological and histological changes in the genitourinary tract of postmenopausal women. Treatment of moderate to severe VVA includes local estrogens, dehydroepiandrosterone (DHEA) and oral ospemifene, a third-generation selective estrogen receptor modulator (SERM). Due to venous thromboembolism (VTE) safety concerns classically associated with the SERM class, and as part of its original marketing authorization approval (MAA), the European Medicines Agency (EMA) requested the performance of a 5-year post-authorization safety study (PASS) to study the incidence rate of VTE among women receiving ospemifene. The results have led to important regulatory changes to ospemifene's labeling, extending its indication and eliminating concerted risk management measures. A panel of experts discussed and reached consensus on the impact of these regulatory changes on clinical practice, reflecting on the reassurance of ospemifene's benefit-risk balance and recommending its positioning as a first-line pharmacological treatment option for moderate to severe VVA together with local therapies. In a scenario where different treatments present similar efficacy and safety profiles, a shared decision between clinician and patient, according to her needs and preferences over time, is fundamental to improve adherence and persistence with sequential treatment, contributing to the achievement of health outcomes.

Sexual functioning in women with functional hypothalamic amenorrhea: exploring the relevance of an underlying polycystic ovary syndrome (PCOS)-phenotype.

PURPOSE: To study sexual function and distress in women with functional hypothalamic amenorrhea (FHA) compared to women with FHA and an underlying polycystic ovary syndrome (PCOS)-phenotype, considering also their psychometric variables. As a secondary aim, we explored the relationship between sexual functioning and hormonal milieu in these women. METHODS: This is a retrospective cross-sectional study conducted on 36 women with typical FHA and 43 women with FHA + PCOS-phenotype. The following validated psychometric questionnaires were administered: Female Sexual Functional Index (FSFI), Female Sexual Distress Scale-Revised (FSDS-R), Body Attitude Test (BAT), Bulimia Investigation Test (BITE), State Anxiety Inventory (STAI), Beck Depression Inventory (BDI), Multidimensional Perfectionism Scale (MPS). Available hormones to formulate FHA diagnosis in the standard routine were considered. RESULTS: Women with typical FHA reported a significantly lower FSFI total score than women with FHA + PCOS-phenotype (95% CI for median 16-21.3 vs. 21.1-24.1, p = 0.002), whereas the FSDS-R score was similar in the two groups (95% CI for median 6-16 vs. 6-16.3). No statistically significant differences were evident in body attitude, state and trait anxiety, depression, bulimic risk, and perfectionism between the two groups, confirming the two FHA groups were superimposable from a psychometric perspective. State anxiety correlated negatively with the FSFI total score in both typical FHA (rho: - 0.33, p = 0.05) and FHA + PCOS-phenotype (rho: - 0.40, p = 0.009). In the entire study population, a positive correlation was found between luteinizing hormone, androstenedione, and 17ß-estradiol and the total FSFI score (rho: 0.28, p = 0.01; rho: 0.27, p = 0.01, rho: 0.27, p = 0.01, respectively). CONCLUSION: Women with FHA showed a very high rate of sexual symptoms as part of their condition, but those with a typical diagnosis displayed a more severe sexual impairment as compared with the FHA + PCOS-phenotype, in spite of a similar psychometric profile. Sexual distress was equally present in both groups (approximately 4 out of 10 women). Further studies should be designed to investigate the potential role of sex hormones, mainly LH-driven androstenedione, in influencing women's sexual functioning.

Vaginal Health: Insights, Views & Attitudes (VIVA-LATAM): results from a survey in Latin America.

OBJECTIVE: To investigate awareness in Latin America, knowledge of postmenopausal vaginal atrophy was evaluated in a sample of women from this region. METHODS: A total of 2509 postmenopausal women aged 55-65 years, resident in Argentina, Brazil, Chile, Colombia and Mexico, completed a structured online questionnaire. RESULTS: Over half the surveyed population (57%) reported experiencing symptoms of vaginal atrophy. Only 6% of the overall cohort attributed symptoms of vaginal atrophy directly to the condition, and 71% did not consider the condition to be chronic, resulting in many women not accessing effective therapy. Half the women (49%) affected by vaginal atrophy had used lubricating gels and creams; 36% had used some form of local hormone treatment. To understand symptoms and/or treatment options for vaginal discomfort, the majority of survey participants (92%) were willing to seek advice from health-care professionals; most (61%) felt/would feel comfortable talking to their doctor about this. CONCLUSION: Many women in Latin America lack knowledge of postmenopausal vaginal atrophy, not appreciating the chronic nature of the condition, and may benefit from dialog initiated by health-care professionals to facilitate greater understanding and increased awareness of the availability of effective treatment.

Vasomotor symptoms in menopause: a biomarker of cardiovascular disease risk and other chronic diseases?

Menopausal disorders may include shorter-term symptoms, such as hot flushes and night sweats (vasomotor symptoms, VMS) and longer-term chronic conditions such as cardiovascular disease (CVD), osteoporosis, and cognitive impairment. Initially, no clear link between the shorter-term symptoms and longer-term chronic conditions was evident and these disorders seemed to occur independently from each other. However, there is a growing body of evidence demonstrating that VMS may be a biomarker for chronic disease. In this review, the association between VMS and a range of chronic postmenopausal conditions including CVD, osteoporosis, and cognitive decline is discussed. Prevention of CVD in women, as for men, should be started early, and effective management of chronic disease in postmenopausal women has to start with the awareness that VMS during menopause are harbingers of things to come and should be treated accordingly.

Effect of ospemifene on moderate or severe symptoms of vulvar and vaginal atrophy.

OBJECTIVES: To determine whether assessment of all moderate-to-severe symptoms at baseline gives a more accurate evaluation of the treatment effect of ospemifene in vulvovaginal atrophy (VVA) than the most bothersome symptom (MBS) approach. METHODS: Data were pooled from two pivotal phase-III clinical trials evaluating the efficacy and safety of oral ospemifene 60 mg/day for the treatment of symptoms of VVA (n = 1463 subjects). Symptoms of vaginal dryness, dyspareunia, and vaginal and/or vulvar irritation/itching reported as moderate or severe at baseline were evaluated. Clinically relevant differences between ospemifene and placebo were analyzed using a four-point severity scoring system and presented as improvement, substantial improvement, or relief. RESULTS: Subjects in these studies reported statistically significant improvement, substantial improvement, and relief for vaginal dryness (p < 0.00001), dyspareunia (p < 0.001) and statistically significant improvement and relief for vaginal and/or vulvar irritation/itching (p < 0.01) from baseline to week 12 with ospemifene compared with placebo. A similar trend was observed for women who reported substantial improvement of vaginal and/or vulvar irritation/itching. CONCLUSIONS: For drug registration purposes, the use of the MBS model is appealing because of its simplicity and ease of scientific validation. However, the MBS model may underestimate the total magnitude of the clinical benefit of ospemifene treatment for symptomatic women suffering from VVA.

The clinical relevance of the effect of ospemifene on symptoms of vulvar and vaginal atrophy.

OBJECTIVES: To explore clinically relevant differences in severity of vulvar and vaginal atrophy (VVA) in postmenopausal women treated with ospemifene compared with placebo. METHODS: Analysis of two multicenter, randomized, double-blind, 12-week phase-III studies in postmenopausal women (40-80 years, with VVA, treated with ospemifene 60 mg/day or placebo (Study 310 and Study 821)). Severity of vaginal dryness and dyspareunia were evaluated using a four-point scoring system and clinically relevant differences between ospemifene and placebo were analyzed and are presented as improvement (reduction in ≥ 1 unit on four-point scoring system), substantial improvement (reduction in 2-3 units on four-point scoring system) and relief (severity score of mild/none after 12 weeks). RESULTS: In Study 310, significantly more women with a most bothersome symptom of dyspareunia had improvement (68.3% vs. 54.1%; p = 0.0255) or relief (57.5% vs. 41.8%; p = 0.0205) in the severity of dyspareunia from baseline to week 12 with ospemifene compared with placebo. For those with a most bothersome symptom of vaginal dryness, significantly more experienced improvement (74.6% vs. 57.7%; p = 0.0101), substantial improvement (42.4% vs. 26.9%; p = 0.0172) and relief (66.1% vs. 49.0%; p = 0.0140) of vaginal dryness from baseline to week 12 with ospemifene compared with placebo. Proportions of women with improvement/substantial improvement/relief of symptoms of vaginal dryness or dyspareunia were similar in Study 821. Clinically relevant differences were noticeable by week 4. CONCLUSIONS: Treatment with ospemifene was consistently associated with greater improvement, substantial improvement or relief in the severity of the most bothersome symptoms of vaginal dryness or dyspareunia compared with placebo.

Ospemifene, a non-oestrogen selective oestrogen receptor modulator for the treatment of vaginal dryness associated with postmenopausal vulvar and vaginal atrophy: a randomised, placebo-controlled, phase III trial.

OBJECTIVE: To evaluate the efficacy and safety of ospemifene, a novel selective oestrogen receptor modulator, in the treatment of vaginal dryness in postmenopausal women with vulvovaginal atrophy (VVA). STUDY DESIGN: A 12 week, multicentre, randomised, double-blind, parallel-group phase III study of women (40-80 years) with VVA and self-reported vaginal dryness as their most bothersome symptom. MAIN OUTCOME MEASURES: The co-primary efficacy endpoints were the change from baseline to Week 12 in (1) percentage of parabasal cells in the maturation index (MI), (2) percentage of superficial cells in the MI, (3) vaginal pH, and (4) severity of vaginal dryness. Safety assessments included physical examination, cervical Papanicolaou test and clinical laboratory analyses. Endometrial thickness and histology was also assessed. RESULTS: A total of 314 women were randomised to once-daily ospemifene 60 mg/day (n=160) or placebo (n=154). Significant improvements in the percentages of parabasal and superficial cells in the MI and vaginal pH were observed with ospemifene compared with placebo (p<0.001 for all parameters). The mean change from baseline in severity score of vaginal dryness reported by women receiving ospemifene compared with those receiving placebo approached statistical significance (p=0.080). Improvements in each of the four co-primary endpoints with ospemifene were statistically significant compared to placebo in the per protocol population. The majority of treatment-emergent adverse events were considered mild to moderate in severity. CONCLUSIONS: Once-daily oral ospemifene 60 mg was effective for the treatment of VVA in postmenopausal women with vaginal dryness.

A 12-week treatment with fractional CO2 laser for vulvovaginal atrophy: a pilot study.

OBJECTIVE: This pilot study aimed to assess the efficacy and feasibility of fractional CO2 laser in the treatment of vulvovaginal atrophy (VVA) in postmenopausal women. METHODS: VVA symptoms were assessed before and after three applications of laser over 12 weeks in 50 women (age 59.6 ± 5.8 years) dissatisfied with previous local estrogen therapies. Subjective (visual analog scale) and objective (Vaginal Health Index Score, VHIS) measures were used during the study period to assess VVA. Quality of life was measured by using the SF-12. A subjective scale to evaluate the degree of pain related to the laser application and the degree of difficulty to perform the laser procedure was used. RESULTS: Fractional CO2 laser treatment was effective to improve VVA symptoms (vaginal dryness, vaginal burning, vaginal itching, dyspareunia, dysuria; p < 0.001) at 12-week follow-up, as well as the VHIS (13.1 ± 2.5 at baseline vs. 23.1 ± 1.9; p < 0.001). Both physical and mental scores of quality of life were significantly improved in comparison with baseline (p < 0.001). Satisfaction with the laser procedure was reported by 42 women (84%) and a minimal discomfort was experienced at the first laser application, mainly because of the insertion and the movements of the probe. Finally, the technique was very easy to perform in all women starting from the second application at week 4 and no adverse events were recorded during the study period. CONCLUSIONS: A 12-week treatment with the fractional CO2 laser was feasible and induced a significant improvement of VVA symptoms by ameliorating vaginal health in postmenopausal women. Further controlled studies should be performed to confirm the present data and to assess the long-term effects of the laser procedure on vaginal tissues.

Impact of vulvovaginal atrophy on sexual health and quality of life at postmenopause.

Vulvovaginal atrophy (VVA) or atrophic vaginitis is a medical challenge because it is under-reported by women, under-recognized by health-care providers and, therefore, under-treated. More or less 50% of postmenopausal women experience vaginal discomfort attributable to VVA. Very recent surveys suggest health-care providers should be proactive in order to help their patients to disclose the symptoms related to VVA and to seek adequate treatment when vaginal discomfort is clinically relevant. Women are poorly aware that VVA is a chronic condition with a significant impact on sexual health and quality of life and that effective and safe treatments may be available. Indeed, female sexual dysfunction and genitourinary conditions are more prevalent in women with VVA. That being so, it is very important to include VVA in the menopause agenda, by encouraging an open and sensible conversation on the topic of intimacy and performing a gynecological pelvic examination, if indicated. According to very recent guidelines for the appropriate management of VVA in clinical practice, it is essential to overcome the vaginal 'taboo' in order to optimize elderly women's health care.

Differences in sexual desire between women with clinical versus biochemical signs of hyperandrogenism in polycystic ovarian syndrome.

The role androgens play in female sexual desire remains unclear. We investigated whether androgen sensitivity or elevated androgen levels contributed to sexual desire using a motivational model of sexual desire. Eighty-five women diagnosed with polycystic ovary syndrome (PCOS) were categorized depending on whether they exhibited clinical symptoms of androgen sensitivity or high biochemical androgen levels. Additionally, instead of looking at desire as a uniform construct, we divided desire based on the reasons why women experienced desire, thus distinguishing desire to have sex for relational purposes from the desire to have sex for mating selection or physical pleasure. Findings confirmed that clinical signs suggesting sensitivity to androgen levels, but not biological levels of androgens per se predicted levels of sexual desire. Moreover, in agreement with our hypothesis, we found support for a relationship between androgen sensitivity and some, but not other aspects of sexual desire. Cues that are most closely related to mating selection were significantly associated with androgen sensitivity, but not cues associated with desiring sex to feel emotionally close or create a love bonding with a partner. This study presents a new way to investigate desire and shows some preliminary findings on the importance to consider androgen sensitivity when investigating the relationship between sexual desire and hormones.

The use of hormone therapy for the maintenance of urogynecological and sexual health post WHI.

BACKGROUND: The loss of estrogen at menopause and the gradual decline in testosterone with age are associated with urogenital atrophy and, as a result, urogenital tract symptoms, including lower urinary tract symptoms and dyspareunia. These symptoms will persist unless treated. OBJECTIVE: To review the prevalence of urogenital tract symptoms and sexual health problems associated with menopause and the role in the use of hormone therapy for the treatment of symptomatic women, with a specific focus on what has been learned since the first publication of the Women's Health Initiative (WHI) estrogen and estrogen + progestin studies. CONCLUSION: Studies support the use of local estrogen therapy, but not systemic estrogen therapy, for the treatment of urge urinary incontinence, overactive bladder and to reduce the number of urinary tract infections. The current evidence does not favor a beneficial effect on stress urinary incontinence. Local estrogen therapy is effective for the treatment of dyspareunia caused by vulvovaginal atrophy. Preliminary studies suggest a potential role for both intravaginal dehydroepiandrosterone and testosterone in the treatment of dyspareunia secondary to vulvovaginal atrophy, however, confirmatory studies are required before either therapy can be recommended. Post WHI, there is a need for medical practitioners to proactively raise the topic of urogynecological and sexual health in order to discuss the most suitable treatment option.

[Association of E2v/DNG as contraceptive choice for a better quality of life of women]. / La scelta contraccettiva a base di E2V/DNG per una migliore qualità di vita delle donne.

The association of estradiol valerate/dienogest (E2V/DNG) is an innovative contraceptive choice with relevant consequences for quality of life of women at all ages. Klaira® (E2V/DNG) combines the use of natural estradiol in a dynamic dosing regimen with a progestin very similar to natural progesterone but with very potent antiproliferative action at the endometrial level. The high contraceptive efficacy of E2V/DNG is associated with a good menstrual cycle control which leads to a novel therapeutic indication in heavy menstrual bleeding. The mild hemostatic and metabolic impact is highly important for women over 35 years, especially when painful syndromes are present (dysmenorrhea and headache), with potential benefits of E2V/DNG, even though the current contraindications of hormonal contraception with ethynilestradiol are still present. In addition, good tolerability and the evidence of beneficial effects on sexual function make E2V/DNG a contraceptive hormonal method with a favourable profile in term of psychophysical well being of women.

Vaginal Health: Insights, Views & Attitudes (VIVA) - results from an international survey.

OBJECTIVE: To assess knowledge of vaginal atrophy among women using the Vaginal Health: Insights, Views & Attitudes (VIVA) survey. METHODS: A structured online questionnaire was used to obtain information from 3520 postmenopausal women aged 55-65 years living in Great Britain, the United States, Canada, Sweden, Denmark, Finland, and Norway. RESULTS: In total, 45% of women reported experiencing vaginal symptoms. Only 4% of women attributed these symptoms to vaginal atrophy, and 63% failed to recognize vaginal atrophy as a chronic condition. Overall, 44% of respondents did not have a gynecologist, but this percentage varied between countries. Most women (75%) felt that vaginal atrophy had a negative impact on life, but this perception also showed country-specific differences. Most Finnish respondents (76%) were satisfied with the amount of information available about vaginal atrophy, compared with just 37-42% of women from other countries. Most women used over-the-counter products for vaginal atrophy symptoms, but specific means of treating the underlying cause were less well known. Almost half (46%) of all respondents lacked knowledge about local estrogen therapy, with women in Great Britain, the United States and Canada being most likely to lack knowledge of such treatment. Overall, 30% of women would consider taking local estrogen therapy, with vaginal tablets being the preferred option in all countries. CONCLUSION: Postmenopausal women have a low understanding of vaginal atrophy. Medical practitioners should proactively raise this topic, help patients to understand that vaginal atrophy is a chronic condition, and discuss treatment options. Country-specific approaches may be required.

Local estrogens for quality of life and sexuality in postmenopausal women with cardiovascular disease.

Urogenital aging and female sexual dysfunction (FSD) are significant problems following menopause. Estrogen decline is one of the key factors contributing to sexual functioning because of its crucial role for genital arousal (vasocongestion and lubrication) and other domains of the sexual response. Several common medical conditions, including cardiovascular disease (CVD), may interfere with women's sexual response across the aging process. FSD is one of the most common CVD-related quality-of-life complications with a major impact on patients' and their sexual partners' life. There is no evidence that FSD may represent an early indication of cardiovascular risk in postmenopausal women. In spite of the high prevalence, FSD remains largely under-recognized and sexual counseling is an important consideration for the proper management of postmenopausal women with CVD. Many local estrogen products are available (creams, tablets, suppositories, pessaries and rings) and are equally effective for treatment of vaginal atrophy. When a history of CVD is present, local estrogens may be safely used to treat urogenital atrophy with a significant improvement of sexual health and quality of life.

Migraine is a risk factor for hypertensive disorders in pregnancy: a prospective cohort study.

The aim was to assess whether women suffering from migraine are at higher risk of developing hypertensive disorders in pregnancy. In a prospective cohort study, performed at antenatal clinics in three maternity units in Northern Italy, 702 normotensive women with singleton pregnancy at 11-16 weeks' gestation were enrolled. Women with a history of hypertensive disorders in pregnancy or presenting chronic hypertension were excluded. The presence of migraine was investigated according to International Headache Society criteria. The main outcome measure was the onset of hypertension in pregnancy, defined as the occurrence of either gestational hypertension or preeclampsia. Two hundred and seventy women (38.5%) were diagnosed with migraine. The majority (68.1%) suffered from migraine without aura. The risk of developing hypertensive disorders in pregnancy was higher in migraineurs (9.1%) compared with non-migraineurs (3.1%) [odds ratio (OR) adjusted for age, family history of hypertension and smoking 2.85, 95% confidence interval (CI) 1.40, 5.81]. Women with migraine also showed a trend to increased risk for low birth weight infants with respect to women without migraine (OR 1.97, 95% CI 0.98, 3.98). Women with migraine are to be considered at increased risk of developing hypertensive disorders in pregnancy. The diagnosis of primary headaches should be taken into account at antenatal examination.

Menopause hormone replacement therapy and cancer risk: an Italian record linkage investigation.

BACKGROUND: The effects of persistence with hormone replacement therapy (HRT) on the risk of hospitalization for cancer and of the route of HRT administration on the risk of breast and colorectal cancer were explored in a large cohort study. PATIENTS AND METHODS: The 73 505 women residing in Lombardia (Italy), aged 45-75 years, who received at least one HRT prescription during 1998-2000 were followed until 2005. Among these, 3687 experienced cancer hospitalization. Proportional hazards model was fitted to estimate the association between cumulative HRT persistence and cancer risk. RESULTS: Compared with women who took HRT for <6 months, those exposed for >2 years showed hazard ratios (HR) of 0.78 (95% confidence interval 0.68-0.92) for colorectal cancer and 1.34 (1.13-1.58) for breast cancer. HR for breast cancer associated with long-term use of transdermal and oral HRT were, respectively, 1.27 (1.07-1.51) and 2.14 (1.43-3.21). CONCLUSIONS: Evidence that long-term use of HRT is associated with increased risk of breast cancer and decreased risk of colorectal cancer is supplied from this study from a southern European population. Our findings indicate that transdermal therapy might have lower effect than oral therapy in increasing breast cancer risk.