The sexuological impact of hormonal contraceptives based on their route of administration.

Evidence on the effects of hormonal contraceptives on female sexuality is conflicting. We enrolled 556 women, divided into six groups: two composed of subjects using a combined hormonal contraceptive (COC) containing 0.020 ("COC20") and 0.030 ("COC30") mg of ethynyl estradiol (EE), "natural", using COC containing 1.5 mg of estradiol (E2), "ring", using a vaginal ring releasing each day 0.015 mg of EE + 0.120 of etonogestrel, "subcutaneous", using a progestin only subcutaneous contraceptive implant releasing etonogestrel and "controls", using no hormonal contraceptive methods. The subjects were required to answer to the McCoy female sexuality questionnaire and were subjected to a blood test for hormonal evaluation. An ultrasound evaluation of the dorsal clitoral artery was also performed. The higher McCoy sexological value were recorded in the subdermal group; significant differences were recorded among the groups in terms of hormone distribution, with the higher levels of androstenedione in subdermal and control groups. The ultrasound evaluation of dorsal clitoral artery shows a significative correlation between pulsatility and resistance indices and orgasm parameters of McCoy questionnaire. The recorded difference in the sexual and hormonal parameters among the studied hormonal contraceptives may guide toward the personalization of contraceptive choice.

Counseling and management of patients requesting subcutaneous contraceptive implants: proposal for a decisional algorithm.

Despite the easy access to contraception today, the rate of unintended pregnancies is still high because of scarce education among women on the methods available and of non-adherence to indications or discontinuation of the contraceptive method chosen. Adherence to contraception can be implemented through counseling programs intended to provide potential users with information regarding all contraceptive options available and to address women's concerns in line with their lifestyle, health status, family planning, and expectations. In here, we evaluate a multi-step decisional path in contraceptive counseling, with specific focus on potential users of long-acting release contraception etonorgestrel. We propose an algorithm about the management of possible issues associated with the use of subcutaneous contraceptive implant, with a special focus on eventual changes in bleeding patterns. We hope our experience may help out health-care providers (HCPs) to provide a brief but comprehensive counseling in family planning, including non-oral routes of contraceptive hormones. Indeed, we believe that a shared and informed contraceptive choice is essential to overcome eventual side-effects and to improve compliance, rate of continuation and satisfaction, especially with novel routes of administration.

Insights into the vulvar component of the genitourinary syndrome of menopause (GSM).

Genitourinary syndrome of menopause is a comprehensive term that groups genital, urinary and sexual signs and symptoms mainly due sex hormone deficiency and aging, with a crucial impact on quality of life of midlife women. While this broad definition captures the common underlying physiopathology and the frequent overlap of symptomatology, improving knowledge about different components of genitourinary syndrome of menopause may be relevant for individualized treatment, with possible implications for efficacy, compliance and satisfaction. This narrative review focuses on the vulvar component of genitourinary syndrome of menopause, highlighting anatomical and functional peculiarities of the vulva that are responsible for some of the self-reported symptoms, as well as specific signs at physical examination. Increasing evidence points towards a pivotal role of vulvar vestibular health in the occurrence of sexual pain, one of the most common and distressing symptoms of genitourinary syndrome of menopause, which should be evaluated with validated scales taking a biopsychosocial perspective. This is an essential step in the recognition of different phenotypes of genitourinary syndrome of menopause and in the assessment of the most effective diagnostic and therapeutic algorithm. Menopausal vulvar health deserves more research into tailored non-hormonal and hormonal treatment options.

Is now the time to reconsider risks, benefits, and limitations of estrogen preparations as a treatment for menstrually related migraine?

INTRODUCTION: Estrogen fluctuations modulate pain threshold and play a pivotal role in the central and peripheral pathogenesis of menstrually related migraine (MRM). Estrogen-withdrawal during the perimenstrual phase of a spontaneous menstrual cycle or the hormone-free interval (HFI) of hormonal treatments seems to be the culprit. AREA COVERED: The authors report the most relevant data on risks, benefits, and limitations of exogenous estrogens as a treatment for MRM considering gynecological comorbidities associated with chronic pelvic pain that may be effectively managed by the use of combined hormonal contraception (CHC). Given that migraine and CHC are both currently known as independent risk factors for stroke, levels of evidence contraindicate CHC in women with migraine with aura, whereas quality of evidence is low in women with migraine without aura, including MRM. Continuous/extended/flexible CHC regimens, shorter HFI, or estrogens supplementation during the HFI/perimenstrual spontaneous phase may be beneficial in women with MRM. EXPERT OPINION: Safety is a main issue, and it is mandatory to investigate the impact of CHC containing natural estrogens, instead of ethinylestradiol, on clinical pattern of MRM and cardiovascular associated risk. Reproductive characteristics may be relevant and should be considered in a multidisciplinary approach to increase the power of endocrine management in MRM.

Pharmacotherapy for female sexual dysfunctions (FSDs): what is on the market and where is this field heading?

INTRODUCTION: Female sexual dysfunctions (FSDs) are common in women of any age and have a huge impact on quality of life and relationships. They have a multifaceted etiology limiting the development of pharmacotherapies with a high rate of effectiveness. Safety issues are also a concern. AREAS COVERED: The authors report the most recent advances in pharmacotherapy for premenopausal and postmenopausal women with a main focus on hypoactive sexual desire disorders (HSDD) and associated sexual symptoms. Good levels of evidence have emerged for psychoactive agents, such as flibanserin and bremelanotide, as well as hormonal compounds (transdermal testosterone). The authors also report briefly on intravaginal DHEA (prasterone), local estrogen therapy (LET), and ospemifene to manage effectively vulvovaginal atrophy/genitourinary syndrome of menopause (VVA/GSM). In addition, they discuss promising therapeutic options highlighting the main reasons that hamper the availability of new labeled products. Finally, they include the importance of the multimodal approach to address FSDs. EXPERT OPINION: Approved pharmacotherapies for FSD are limited. Validated multidimensional instruments and adequate objective measures of physical and mental responses to sexual external and internal incentives are mandatory to identify women suitable to chronic or on-demand treatments and to assess their pattern of response in research and practice.

Hyaluronic Acid: A Valid Therapeutic Option for Early Management of Genitourinary Syndrome of Menopause in Cancer Survivors?

Genitourinary syndrome of menopause (GSM) is a chronic condition affecting a large number of women, with a major impact on their urogenital health and sexual function. It occurs at midlife because estrogen levels decline with menopause enhancing aging-related changes of the functional anatomy of the urogenital system. Unfortunately, GSM may occur early in the lifespan of women or be exacerbated following anticancer treatments, such as chemotherapy, ionizing radiation, or surgical removal of reproductive organs. Symptoms of GSM are often under-reported by women, under-estimated and under-diagnosed by health care providers (HCPs), and subsequently under-treated, despite their profound negative impact on the quality of life. The mainstay of vaginal treatments is local estrogen therapy (LET) ensuring an effective management of moderate to severe symptomatic GSM. However, LET is generally contraindicated in women with a history of hormone receptor positive cancer, due to the fear of increased recurrence or possible interference with endocrine adjuvant therapies. Among non-hormonal treatments, hyaluronic acid-based moisturizers have shown promising clinical results both in healthy women and in cancer patients or survivors. Its strong water-binding properties provide lubricating and moisturizing effects, which contribute to maintaining a proper level of hydration and viscoelasticity in several body parts, including the urinary tract and genital tissues. Hyaluronic acid-based moisturizers are effective, safe, and well tolerated; therefore, they may represent a valid option for the early management of GSM-associated symptoms in every woman with a history of cancer who is unable or unwilling to undergo hormone-based therapies. Hence, the aim of this review was to provide an overview of GSM etiology and treatment in women with natural or iatrogenic menopause, with a focus on the use of hyaluronic acid as a prophylactic treatment in the context of an integrated management protocol for cancer patients.

Medical Treatment of Female Sexual Dysfunction.

Female sexual dysfunction (FSD) comprises multiple overlapping sexual disorders with a multifaceted cause within the frame of the biopsychosocial model. Health care providers can screen for FSD according to their level of expertise and deliver at least basic counseling before eventually referring to sexual medicine specialists for specific care. The therapeutic algorithm comprises a multidisciplinary approach, including pharmacologic and nonpharmacologic management. Flibanserin and bremelanotide are psychoactive agents indicated for the treatment of generalized acquired hypoactive sexual desire disorder (HSDD) in premenopausal women, whereas transdermal testosterone is effective on HSDD in postmenopausal women. Menopause hormone therapy (systemic and local) is the mainstay for individualized management of women at midlife.

Relationship between personality traits and sexual function in symptomatic postmenopausal women.

INTRODUCTION: Female sexual function relies on a complex interplay of physical, psychosocial, and neurobiological factors. Over the last decades, increasing attention has been paid to the influence of personality traits on general health and many aspects of quality of life, including sexuality. OBJECTIVE: To assess whether dimensions of the personality are related to the domains of sexual function (desire, arousal, lubrication, orgasm, satisfaction, and pain) in symptomatic postmenopausal women. Mood was also investigated to explore its association with female sexual dysfunction (FSD). METHODS: Validated questionnaires to assess sexual function [the Female Sexual Functioning Index (FSFI)], mood [the State-Anxiety Inventory (STAI), and Zung Self Rating Depression Scale (SDS)], and personality traits [the Tridimensional Personality Questionnaire (TPQ)] were filled in by 130 early postmenopausal women experiencing hot flushes (≥30/week). RESULTS: 61.5 % (n = 80) of the women had an FSFI total score lower than 26.55, the standard cut-off for FSD. A clinical state of anxiety was present in 53.8 % (n = 70), whereas only 12.3 % (n = 16) showed clinically relevant depressive symptoms. According to the FSFI cut-off score, women with sexual disorders had statistically significantly higher levels of anxiety, depression (p < 0.001 for both), and harm avoidance (HA) (p = 0.004) than women without such disorders. Significantly higher levels of anxiety were found in women in the lower quartile (LQ) of the distribution of the total FSFI score than in women in both the interquartile range (IQR) and in the upper quartile (UQ) (p < 0.05). Moreover, women in the UQ had a lower grade of depression and HA than others (p < 0.05). The Sobel test showed that the personality trait HA significantly mediated the relationship between anxiety and FSFI total score (Z = -2.19, p < 0.05) and between depression and FSFI total score (Z = -2.35, p < 0.05). CONCLUSIONS: The present data suggest the personality trait HA is relevant to sexual function and mediates the impact of mood on FSD in symptomatic menopausal women. In clinical practice, the use of validated psychometric tools for mood screening is useful to establish appropriate diagnosis and treatment of sexual disorders in menopausal women. Moreover, the assessment of personality traits could provide additional information that directs clinicians towards an increasingly tailored and multidimensional treatment of FSD.

Menopause and female sexual dysfunctions.

Biological and psycho-relational factors contribute equally to the development of sexual symptoms and associated distress, a key element to diagnose female sexual dysfunctions (FSDs) in menopausal women. Consultation at midlife represents an optimal time to discuss sexual life, and healthcare providers have to be proactive in rising the conversation, as patients may not report their sexual concerns spontaneously. An accurate sexual history is essential to characterize the primary symptom, determine the impact on patient's quality of life and identify risk and precipitating factors. Among FSDs, hypoactive sexual desire disorder is very frequent at midlife together with genitourinary syndrome of menopause, a chronic condition negatively affecting the full sexual response. A multidimensional approach targeted to the patient's characteristics, goals and expectations is mandatory and should start from educative counselling and correction of modifiable risk factors. When specific treatments are required, they should include non-pharmacological and pharmacological options, often prescribed in combination to address concomitantly the biological and psychosocial components of FSDs.

The role of hormone therapy in urogenital health after menopause.

Menopause represents an endocrine challenge to urogenital health, as oestrogens deprivation and androgens decline significantly contributes to age-related involution of vulvovaginal tissues and lower urinary tract. Genitourinary syndrome of menopause (GSM) is a clinical entity including the chronic and progressive condition of vulvovaginal atrophy (VVA) and encompassing both anatomical and functional consequences of menopause. The term GSM describes genital, sexual and urinary symptoms with a detrimental impact on quality of life (QOL). Several treatment options are available, but many barriers are still present to adequately diagnose and treat GSM. This review aims to present current evidences about epidemiology, aetiology, diagnosis and treatment of GSM, with a focus on prescription medications [low-dose local oestrogen therapy (LET), prasterone (DHEA) and the SERM ospemifene] for urogenital symptoms in healthy postmenopausal women and in special populations, including women with premature ovarian insufficiency (POI) and breast cancer survivors (BCS).

Psychosexual well-being in women using oral contraceptives containing drospirenone.

Considerable advances have been made in hormonal contraception in recent years, geared at maximizing compliance and minimizing discontinuation. In oral contraceptive (OC) formulations, the estrogenic component, generally ethinyl estradiol (EE), has been reduced significantly and newer progestins like dienogest and drospirenone (DRSP), compounds with different molecular structures, have been introduced; in addition, new regimens (extended, flexible, 24/4 formats instead of the standard 21/7 format) and innovative delivery systems (vaginal rings, transdermal patches, subcutaneous implants and intrauterine devices) are available. The multitude of choices allows hormonal contraception to be tailored to the individual woman in order to obtain non-contraceptive benefits, without significant side effects, and also a favorable risk/benefit profile for her general and reproductive health. Over the past few years, new OC formulations combining DRSP (3 mg), a unique progestin with both antimineralocorticoid and antiandrogenic activities, with estrogen (30 mcg or 20 mcg EE), in two regimens (24/4 and 21/7) of active pills in a 28-day cycle, have shown positive effects on water retention-related weight gain and physical, emotional and psychosexual well-being. It seems likely that the use of a low-dose, well-balanced OC and the shorter 4-day hormone-free interval may minimize the side effects that can impair quality of life and thus increase women's compliance with hormonal contraception therapy.

Addressing Vulvovaginal Atrophy (VVA)/Genitourinary Syndrome of Menopause (GSM) for Healthy Aging in Women.

Vaginal health is an essential component of active and healthy aging in women at midlife and beyond. As a consequence of hormonal deprivation and senescence, the anatomy and function of urogenital tissues are significantly affected and vulvovaginal atrophy (VVA) may occur. In a high proportion of postmenopausal women, progressive and chronic VVA symptoms have a strong impact on sexual function and quality of life. The new definition of genitourinary syndrome of menopause (GSM) comprises genital symptoms (dryness, burning, itching, irritation, bleeding), sexual symptoms (dyspareunia and other sexual dysfunctions) and urinary symptoms (dysuria, frequency, urgency, recurrent urinary infections). Many variables (age, sexual activity and partnership status) influence the clinical impact VVA/GSM symptoms and attitudes of elderly women to consult for receiving effective treatments. Psychosocial factors play a critical role in sexual functioning, but the integrity of the urogenital system is as well important affecting many domains of postmenopausal women's health, including sexual function. Several international surveys have extensively documented the need to improve VVA/GSM management because of the strong impact on women's daily life and on couple's intimacy. Health care providers (HCPs) need to be proactive in the early recognition of VVA/GSM in order to preserve urogenital and sexual longevity, by using hormonal and non-hormonal strategies. The clinical diagnosis is based on genital examination to identify objective signs and on the use of subjective scales to rate most bothersome symptoms (MBS), especially vaginal dryness. Recent studies point to the importance of addressing VVA/GSM as a potential early marker of poor general health in analogy with vasomotor symptoms. Therefore, a standard of VVA/GSM care in elderly women is desirable to enhance physical, emotional and mental well-being.

Female sexual dysfunction (FSD): Prevalence and impact on quality of life (QoL).

Female sexual dysfunction (FSD) and quality of life (QOL) are both multidimensional and have a bidirectional relationship across the reproductive life span and beyond. Methodological difficulties exist in estimating the real prevalence of FSD because it is hard to determine the level of distress associated with sexual symptoms in a large-scale survey. Approximately 40-50% of all women report at least one sexual symptom, and some conditions associated with hormonal changes at menopause, such as vulvovaginal atrophy (VVA) and hypoactive sexual desire disorder (HSDD), have a significant impact on sexual function and QOL. Sexual distress peaks at midlife, declines with age and is strongly partner-related. Many postmenopausal women are still sexually active, especially if they are in a stable partnership. Even though sexual functioning is impaired, a variety of psychosocial factors may maintain sexual satisfaction. That being so, health care providers (HCPs) should proactively address sexual symptoms at midlife and in older women, from a balanced perspective. Adequate counselling should be offered. Women with distressing symptoms may benefit from tailored hormonal and non-hormonal therapies, whereas women without distress related to their sexual experiences should not receive any specific treatment.

Maintaining sexuality in menopause.

Sexual health in the menopause is a medical challenge because the progressive decline of sexual hormones interacts with the aging process and many psychosocial stressors modulate vulnerability for sexual symptoms (low sexual desire, poor arousal and lubrication, dyspareunia, orgasmic dysfunction and lack of satisfaction). In clinical practice, a coordinated approach is needed to optimally manage the risk for developing female sexual dysfunction (FSD), especially when chronic conditions are present. Biomedical and psychosocial interventions include general education, recognition of signs and symptoms, promotion of health, attention to the partner and individualization of treatment. Counselling to overcome personal and relational difficulties should be always combined with hormonal and non-hormonal strategies to maximize biological signals driving the sexual response. By enhancing women's abilities to cope with sexual changes at midlife, health care providers may significantly optimize healthy aging and partnership.

Effect of a contraceptive pill containing estradiol valerate and dienogest (E2V/DNG) in women with menstrually-related migraine (MRM).

BACKGROUND: Combined hormonal contraception might worsen migraine in sensitive women, especially during the free-hormone interval, and raise concerns about the vascular risk. The characteristics of a contraceptive pill containing estradiol valerate/dienogest (E2V/DNG) might be of potential benefit in women with menstrually related migraine (MRM) who choose to use oral contraception for birth control. STUDY DESIGN: This was a prospective diary-based pilot study. Thirty-two women (age >35 years) [n=18 who had never used combined oral contraceptives (COCs) and n=14 who had previously used COCs] diagnosed with MRMs according to the International Headache Society criteria were included. During the observational period, women filled in a diary with the clinical characteristics of migraine attacks. After a three-cycle run-in period, each subject received a COC containing E2V/DNG (Qlaira®/Natazia®; Bayer HealthCare, Berlin, Germany) administered using an estrogen step-down and progestogen step-up approach. Follow-up evaluations were scheduled at the last cycle of run-in and at the third and sixth cycles of treatment. RESULTS: The number of migraine attacks was significantly reduced at the third (p<.001) and sixth cycles (p<.001) in comparison with the run-in period. A similar result was evident for the duration (p<.001 at the third and p<.001 at the sixth cycle) as well as for the severity of head pain (p<.001 at the third and p<.001 at the sixth month). Indeed, a significantly lower number of analgesics were used at the third cycle (p<.001) in comparison with baseline, and a further decrease was evident at the sixth cycle (p<.001) in comparison with the third cycle of E2V/DNG use. Interestingly, duration and severity of head pain were significantly correlated with the number of days of dysmenorrhea at the third cycle (r=.89, p=.000 and r=.67, p=.02; respectively) and at the sixth cycle (r=.76, p=.000 and r=.62, p=.04; respectively) in women without complete remission of menstrual cramps during the study period. CONCLUSIONS: The present diary-based pilot study indicates that the use of a pill containing EV2/DNG for six cycles has a positive effect in women with MRM and suggests an association between dysmenorrhea with COCs use as a potential feature of refractory head pain.

Management of hypoactive sexual desire disorder in women: current and emerging therapies.

Hypoactive sexual desire disorder (HSDD) is a common multifactorial condition which is characterized by a decrease in sexual desire that causes marked personal distress and/or interpersonal difficulty. The general idea that HSDD is a sexual dysfunction difficult to treat is due to the large number of potential causes and contributing factors. Indeed, a balanced approach comprising both biological and psycho-relational factors is mandatory for accurate diagnosis and tailored management in clinical practice. There are currently no approved pharmacological treatments for premenopausal women with HSDD, while transdermal testosterone is approved in Europe for postmenopausal women who experience HSDD as a result of a bilateral oophorectomy. Even though the role of sex hormones in modulating the sexual response during the entire reproductive life span of women is crucial, a better understanding of the neurobiological basis of sexual desire supports the idea that selective psychoactive agents may be proposed as nonhormonal treatments to restore the balance between excitatory and inhibitory stimuli leading to a normal sexual response cycle. We conclude that the ideal clinical approach to HSDD remains to be established in term of efficacy and safety, and further research is needed to develop specific hormonal and nonhormonal pharmacotherapies for individualized care in women.

Menopause and sexual desire: the role of testosterone.

The present short review underlines the role of testosterone (T) in the motivational and satisfaction components of women's sexuality and critically discusses the strategies to treat hypoactive sexual desire disorder (HSDD), a condition of low desire associated with personal and/or interpersonal difficulties, which is more common in surgical menopausal women. There are multiple ways androgens target the brain regions (hypothalamic, limbic and cortical) involved in sexual function and behaviour. Even though circulating available androgens have been implicated in several domains of sexual response, they seem to be related weakly to symptoms, such as low sexual desire, poor sexual arousal, orgasm and diminished well-being in postmenopausal women. The possibilities of treating low sexual desire/HSDD are multifaceted and should include the combination of pharmacological treatments able to maximize biological signals driving the sexual response, and individualized psychosocial therapies in order to overcome personal and relational difficulties. Transdermal T has been shown to be effective at a dose of 300 µg/day both in surgically and naturally menopausal women replaced with estrogen or not, without any relevant side-effects. However, the decision to treat postmenopausal women with HSDD with T is mainly based on clinical judgement, after informed consent regarding the unknown long-term risks.

Hormonal and psycho-relational aspects of sexual function during menopausal transition and at early menopause.

OBJECTIVE: The aim of the present observational, cross-sectional study was to examine the effects of hormonal and psycho-relational variables on sexual function during menopausal transition and at early postmenopause in women with hot flushes. STUDY DESIGN: The sample comprised 138 women referred to a clinic for the treatment of hot flushes. They were categorised according to their stage of menopausal transition using the STRAW criteria: early menopausal transition (EMT) if their menstrual cycle was 7 or more days different from normal; late perimenopause (LMT) if they had experienced 60 days or more of amenorrhoea; and early postmenopause (EPM) if their amenorrhoea had lasted for at least 12 months but less than 4 years. MAIN OUTCOME MEASURES: Sexual function was measured by using the Female Sexual Function Index (FSFI), while anxiety (state and trait), depression, eating disorder and marital adjustment were evaluated by validated self-report questionnaires. Levels of free testosterone (FT), dehydroepiandrosterone sulfate (DHEAS) and estradiol (E2) were also measured. RESULTS: Overall sexual function varied significantly with stage of menopause, with total FSFI score less in EPM than in EMT (p=.009). A similar pattern was evident on FSFI sub-scales for sexual desire (p=.02), arousal (p=.01) orgasm (p=.01) and also pain (p=.02), but not for lubrication and satisfaction. Ratings for anxiety, depression and eating disorder did not differ across the menopausal sub-groups, and neither did ratings of marital adjustment. Both FT (p=.01) and DHEAS (p=.03) levels were slightly reduced at EPM in comparison with EMT, as were E2 levels (p=.001 EMT versus LMT; p=.0001 LMT versus EPM). In multiple regression analyses, plasma FT level was the only factor to predict FSFI full score (beta=.48; p=0.004) in women at EMT, while in women at LMT the depression score was the only factor to do so (beta=-.62; p=0.0001). The best model predicting FSFI full score at EPM included levels of DHEAS and E2 levels and state anxiety score. CONCLUSIONS: Hormonal and some psychological variables are relevant to sexual function in symptomatic women during menopausal transition and at early menopause but their role differs with the specific stage of reproductive ageing.