Thyroid diseases and female sexual dysfunctions.

INTRODUCTION: Female sexual dysfunctions (FSDs) have received little attention in the context of thyroid diseases, despite the high prevalence of both conditions. OBJECTIVES: This review aims to update and summarize the state of knowledge on the association between thyroid diseases and FSDs and to investigate the complex mechanisms through which thyroid hormone imbalance can impact female sexual health in the context of the biopsychosocial model. METHODS: A comprehensive literature search was performed through the PubMed, MEDLINE, and Scopus databases, using the following keywords: "female sexual function," "sexual dysfunction," "hypoactive sexual desire disorder," "thyroid disease," "thyroiditis," "hypothyroidism," and "hyperthyroidism." RESULTS: To date, well-designed studies that describe the relationship between FSDs and thyroid disorders are lacking. However, despite the limitations on available studies, current data indicate that sexual alterations are frequently associated with thyroid diseases in women. A complex interplay of direct and indirect hormonal and nonhormonal mechanisms has been hypothesized, including hormonal changes, neurotransmitter imbalance, reduced nitric oxide release, mood disorders, and other systemic consequences of both hypothyroidism and hyperthyroidism. Thyroid hormone receptors have also been identified in the genitourinary system. CONCLUSIONS: In a clinical setting, physicians should investigate the sexuality of patients consulting for thyroid disease. At the same time, an evaluation of thyroid function should be performed in patients presenting with FSD, especially after menopause, when the risk of thyroid diseases and FSDs increases strongly.

The metrics maze in science: navigating academic evaluation without journalistic pressures.

In recent years a troubling trend has emerged in the medical research field, notably in reproductive medicine, manifesting an increased emphasis on quantity over quality in articles published. The pressure to collect copious publication records risks compromising meticulous expertise and impactful contributions. This tendency is exemplified by the rise of 'hyper-prolific researchers' publishing at an extraordinary rate (i.e. every 5 days), prompting a deeper analysis of the reasons underlying this behaviour. Prioritizing rapid publication over Galileo Galilei's systematic scientific principles may lead to a superficial approach driven by quantitative targets. Thus, the overreliance on metrics to facilitate academic careers has shifted the focus to numerical quantification rather than the real scientific contribution, raising concerns about the effectiveness of the evaluation systems. The Hamletian question is: are we scientist or journalist? Addressing these issues could necessitate a crucial re-evaluation of the assessment criteria, emphasizing a balance between quantity and quality to foster an academic environment that values meaningful contributions and innovation.

Treating moderate-to-severe menopausal vasomotor symptoms with fezolinetant: analysis of responders using pooled data from two phase 3 studies (SKYLIGHT 1 and 2).

OBJECTIVES: The aims of the study were to further characterize the efficacy of fezolinetant for the treatment of moderate-to-severe vasomotor symptoms (VMS) due to menopause using responder analysis and to investigate whether efficacy, not adjusted for placebo, resulted in clinically meaningful within-patient change. METHODS: This prespecified analysis used pooled data from two phase 3, randomized, double-blind, placebo-controlled studies (SKYLIGHT 1 and 2). Responders were those experiencing ≥50%, ≥75%, ≥90%, or 100% reduction in VMS frequency from baseline to weeks 4 and 12. Responder analysis was performed for patient-reported outcome (PRO) measures to evaluate participants achieving a clinically meaningful within-patient change (not placebo adjusted) at week 4 and 12 versus baseline. Single responders were based on outcomes of VMS frequency, Patient-Reported Outcomes Measurement Information System Sleep Disturbance-Short Form 8b Total Score, Menopause-Specific Quality of Life (MENQoL) Total Score, and MENQoL VMS Domain Score. Double and triple responder analyses combined VMS frequency plus one or more of the PRO. Patient Global Impression of Change VMS was deemed a suitable anchor measure for meaningful within-patient change in VMS frequency. RESULTS: A greater proportion of fezolinetant-treated versus placebo-treated participants had ≥50%, ≥75%, ≥90%, or 100% reduction in VMS frequency from baseline to weeks 4 and 12. A greater proportion of responders were observed in the fezolinetant groups versus placebo at week 12 in all four single responder analyses. In the double and triple responder analyses, odds ratios were supportive of a beneficial effect for both doses of fezolinetant versus placebo. CONCLUSIONS: Fezolinetant was associated with significantly higher within-patient clinically meaningful improvement in important PRO, including VMS frequency, PROMIS SD SF 8b Total Score, MENQoL Total Score, and MENQoL VMS Domain Score.

From couplepause to doublepause: the impact of midlife physical, psychological, and social changes on the sexual life of aging couples.

INTRODUCTION: Midlife men and women are facing frequent sexual problems that affect not only individuals' sexual health but also the sexual health of aging couples. OBJECTIVES: To review the main sexual life challenges faced by midlife couples, to present the concepts of couplepause and doublepause as 2 new paradigms to address the sexual health needs of aging couples, and to discuss key aspects in couple-focused care. METHODS: An online meeting attended by 5 European experts in sexual health was carried out in June 2023 to discuss the topic. The conversation centered on their clinical experience and expert opinion. Additionally, the indexed literature was reviewed to endorse and complement the expert opinions obtained in the aforementioned meeting. RESULTS: Midlife men and women face physical, psychological, and sociocultural changes that affect their sexual activity. These changes may be experienced differently between genders. Both members of a couple may experience age-related changes concurrently or in an unsynchronized manner affecting their sexual health. Communication, sharing expectations, defining sexual dynamics, and couple goals are determinant for the sexual health of a midlife couple. Couplepause and doublepause are 2 new complementary paradigms that effectively address the sexual health needs of aging couples as a unit, considering physical, psychological, cultural, social, and dyadic-related factors. Couple-centered strategies should promote open communication about couple intimacy issues, understanding the diverse expectations according to gender and orientation, communication styles, and goals. The following are identified as crucial aspects to promote couple-focused care: education and training of health care professionals, the provision of information to aging couples, physician involvement in addressing sexual problems, the need for collaboration across medical specialties, and the development of effective tools and strategies. CONCLUSIONS: The sexual problems of aging couples should be managed following couple-centered strategies that effectively address their sexual health needs as a couple.

Fezolinetant treatment of moderate-to-severe vasomotor symptoms due to menopause: effect of intrinsic and extrinsic factors in two phase 3 studies (SKYLIGHT 1 and 2).

OBJECTIVE: This study aimed to assess the efficacy of the neurokinin 3 receptor antagonist, fezolinetant, according to several intrinsic (individual related) and extrinsic (external influence) factors that may influence the frequency and severity of moderate-to-severe vasomotor symptoms (VMS) using pooled 12-week data from SKYLIGHT 1 and 2. METHODS: SKYLIGHT 1 and 2 were two phase 3, randomized, double-blind studies conducted from July 2019 to August 2021 (SKYLIGHT 1) or April 2021 (SKYLIGHT 2). Participants were initially randomized to receive daily doses of placebo, fezolinetant 30 mg, or fezolinetant 45 mg. After 12 weeks, placebo participants were rerandomized to receive fezolinetant 30 mg or 45 mg, whereas those receiving fezolinetant continued on the same dose. Change in VMS frequency from baseline to week 12 was used to assess efficacy according to several intrinsic and extrinsic factors. Overall efficacy and safety were also investigated. RESULTS: Overall, 1,022 individuals were included. Fezolinetant was efficacious in reducing VMS frequency across all intrinsic and extrinsic factors. Efficacy was most notable for participants who self-identify as Black (least squares mean difference for fezolinetant 45 mg versus placebo, -3.67; 95% CI, -5.32 to -2.01), current smokers (-3.48; -5.19 to -1.77), and current alcohol users (-3.48; -4.42 to -2.54). Overall efficacy was -2.51 (95% CI, -3.20 to -1.82) for fezolinetant 45 mg versus placebo. Similar findings were observed for the fezolinetant 30 mg dose. Comparable incidences of treatment-emergent adverse events were observed for placebo (132 of 342 individuals [38.6%]), fezolinetant 30 mg (132 of 340 individuals [38.8%]), and fezolinetant 45 mg (135 of 340 individuals [39.7%]). CONCLUSIONS: None of the intrinsic and extrinsic factors analyzed substantially reduced the efficacy response to fezolinetant in SKYLIGHT 1 and 2. These data provide additional confidence for using fezolinetant in a diverse population of individuals with VMS.

Expert opinion on the use of contraception in people with multiple sclerosis.

BACKGROUND: Current guidance on the selection of appropriate contraception for people with multiple sclerosis (PwMS) is lacking. OBJECTIVE: To address this gap, an expert-led consensus program developed recommendations to support clinicians in discussing family planning and contraception with women and men with multiple sclerosis (MS). METHODS: A multidisciplinary steering committee (SC) of 13 international clinical experts led the program, supported by an extended faculty of 32 experts representing 18 countries. A modified Delphi methodology was used for decision-making and consensus-building. The SC drafted 15 clinical questions focused on patient-centered care, selection of contraception, and timing of stopping/starting contraception and disease-modifying therapies (DMTs). Statements addressing each question were drafted based on evaluation of published evidence and the experts' clinical experience. Consensus was reached if ⩾75% of respondents agreed (scoring 7-9 on a 9-point scale) with each recommendation. RESULTS: Consensus was reached on 24 of 25 proposed recommendations, including how and when to discuss contraception, types and safety of contraceptives, and how to evaluate the most appropriate contraceptive options for specific patient groups, including those with significant disability or being treated with DMTs. CONCLUSION: These expert recommendations provide the first practical, relevant, and comprehensive guidance for clinicians on the selection of contraception in PwMS.

Vulvovaginal atrophy in women with and without a history of breast cancer: Baseline data from the PatiEnt satisfactiON studY (PEONY) in Italy.

OBJECTIVES: To assess clinical characteristics of postmenopausal women with moderate/severe vulvovaginal atrophy, as well as its impact on sexual function, well-being, and quality of life, and to provide an overview of most used treatments. STUDY DESIGN: Ongoing longitudinal, observational study conducted in 17 Italian gynecology centers, involving women already treated or initiating a local vaginal estrogen therapy or ospemifene. We report baseline data for women with and without a history of breast cancer. Participants filled in self-reported questionnaires at study entry. MAIN OUTCOME MEASURES: Severity of vulvovaginal atrophy; ongoing treatments; patient-reported outcomes, including severity of symptoms, Day-to-Day Impact of Vaginal Aging (DIVA), Female Sexual Function Index (FSFI), Female Sexual Distress Scale-Revised (FSDS-R), and SF-12® Health Survey. RESULTS: Overall, 334 women (20.4 % with a history of breast cancer) started or continued local therapy (61.1 %) or ospemifene (38.8 %) at study entry. Vulvovaginal atrophy was severe in 28.6 %, and was responsible for severe symptoms, particularly vulvar dryness with burning or irritation and pain during sexual intercourse. Both sexual dysfunction (FSFI≤26) (81.5 %) and sexual distress (FSDS-R ≥ 11) (74.4 %) were common. A reduction in the SF-12 mental component score was documented. Women with breast cancer more often had severe vulvovaginal atrophy (41.2 %), had more severe symptoms, and the impact of vaginal symptoms on emotional well-being, sexual functioning and self-concept/body image was greater. The majority of them (83.8 %) received ospemifene as a treatment. CONCLUSIONS: Moderate/severe vulvovaginal atrophy is a common, often neglected condition with an impact on QoL and sexuality, particularly in women with a history of breast cancer. It is important to alleviate the burden associated with the disease.

Obesity and menopause.

Obesity is not a choice or a result of lack of willpower, but a multifactorial, chronic, progressive, and relapsing disease. During menopause, hormonal and body composition changes lead to greater visceral adiposity, that aggravates women's health at a cardiometabolic, mechanic and mental level. Adiposity has been identified as an important modifier of reproductive hormones. During female midlife, obesity has been associated with menstrual cycle alterations (anovulatory cycles ending with abnormal bleedings), menopausal symptoms including hot flashes, poor quality of sleep, aches and joint pain, genitourinary symptoms, and reduced quality of life. However, the relationships between weight, the menopausal process, aging, and hormone levels remain poorly understood. Women with obesity have an increased risk of thromboembolic disease when using menopause hormone therapy (MHT), and it is probably the main medical condition to prescribe or not MHT. However, this risk depends on the route and type of MHT. The use of estrogen-only or combined transdermal MHT does not increase the risk of a thrombotic event in women with obesity.

Fezolinetant impact on health-related quality of life for vasomotor symptoms due to the menopause: Pooled data from SKYLIGHT 1 and SKYLIGHT 2 randomised controlled trials.

OBJECTIVE: To assess the effect of fezolinetant treatment on health-related quality of life using pooled data from SKYLIGHT 1 and 2 studies. DESIGN: Prespecified pooled analysis. SETTING: USA, Canada, Europe; 2019-2021. POPULATION: 1022 women aged ≥40 to ≤65 years with moderate-to-severe vasomotor symptoms (VMS; minimum average seven hot flushes/day), seeking treatment for VMS. METHODS: Women were randomised to 12-week double-blind treatment with once-daily placebo or fezolinetant 30 or 45 mg. Completers entered a 40-week, active extension (those receiving fezolinetant continued that dose; those receiving placebo re-randomised to fezolinetant received 30 or 45 mg). MAIN OUTCOME MEASURES: Mean changes from baseline to weeks 4 and 12 on Menopause-Specific Quality of Life (MENQoL) total and domain scores, Work Productivity and Activity Impairment questionnaire specific to VMS (WPAI-VMS) domain scores, Patient Global Impression of Change in VMS (PGI-C VMS); percentages achieving PGI-C VMS of 'much better' (PGI-C VMS responders). Mean reduction was estimated using mixed model repeated measures analysis of covariance. RESULTS: Fezolinetant 45 mg mean reduction over placebo in MENQoL total score was -0.57 (95% confidence interval [CI] -0.75 to -0.39) at week 4 and -0.47 (95% CI -0.66 to -0.28) at week 12. Reductions were similar for 30 mg. MENQoL domain scores were also reduced and WPAI-VMS scores improved. Twice as many women receiving fezolinetant reported VMS were 'much better' than placebo based on PGI-C VMS assessment. CONCLUSIONS: Fezolinetant treatment was associated with improvement in overall QoL, measured by MENQoL, and work productivity, measured by WPAI-VMS. A high proportion receiving fezolinetant felt VMS were 'much better' based on PGI-C VMS responder analysis.

Efficacy and safety of a device that combines multipolar radiofrequency with pulsed electromagnetic field for the treatment of vulvovaginal atrophy: a randomized, sham-controlled trial.

BACKGROUND: Vulvovaginal atrophy (VVA) negatively affects the sexual well-being and quality of life of postmenopausal women, yet it is underreported and undertreated. AIM: The study sought to investigate the efficacy and safety of a nonablative, noncoagulative multipolar radiofrequency (RF) and pulsed electromagnetic field-based device (PEMF) in treatment of symptoms related to VVA. METHODS: Seventy-six women ≥19 years of age with symptoms associated with VVA were enrolled into this prospective, randomized, sham-controlled, multicenter clinical study. Subjects were randomized to receive 3 RF + PEMF treatments (active group) or sham treatments (sham group) delivered to vaginal tissue at monthly intervals. The Vaginal Health Index (VHI), along with the Female Sexual Function Index (FSFI), subject sexual satisfaction and vaginal laxity (VL) score, treatment-associated pain, and adverse events were assessed at 4 follow-up (FU) visits between 1 and 12 months after treatment. OUTCOMES: Changes from baseline VHI, pH, FSFI, VL, and sexual satisfaction scores between the active and sham groups were compared before and after treatment. RESULTS: Mean VHI scores in the active group were significantly better compared with the sham group after treatment at all but the last FU visit (P < .001). A greater decrease in pH (active over sham) was seen at 1 and 4 months after treatment (P < .05). FSFI improvement was shown in the active group; however, it was not significantly better than sham improvement at all FU visits. Subject sexual satisfaction in the active group showed better improvement over sham at all FU visits (P < .05), while VL evaluations saw greater improvement in the active group at 4, 6, and 12 months posttreatment (P < .05). Treatment satisfaction was greater in the active group and pain was minimal in both groups. No serious adverse effects were reported. CLINICAL IMPLICATIONS: As a noninvasive alternative to traditional surgical and topical procedures, 3 sessions of noninvasive combination RF/PEMF safely demonstrated improvement in symptoms related to VVA. STRENGTHS AND LIMITATIONS: This study was strengthened by the randomized, sham-controlled design; large sample size; and extended FU period. The study assessments were decreased at later FU visits due to the global COVID pandemic, and this was a key limitation to the study. CONCLUSION: Nonablative, noncoagulative multipolar RF/PEMF therapy was safe, improved symptoms associated with VVA, and improved female sexual function while yielding high subject satisfaction.

Is motherhood still possible after pelvic carbon ion radiotherapy? A promising combined fertility-preservation approach.

INTRODUCTION: Preserving the endocrine and reproductive function in young female cancer patients undergoing pelvic radiation is a significant challenge. While the photon beam radiation's adverse effects on the uterus and ovaries are well established, the impact of pelvic carbon ion radiotherapy on women's reproductive function is largely unexplored. Strategies such as oocyte cryopreservation and ovarian transposition are commonly recommended for safeguarding future fertility. METHODS: This study presents a pioneering case of successful pregnancy after carbon ion radiotherapy for locally advanced sacral chondrosarcoma. RESULTS: A multidisciplinary approach facilitated the displacement of ovaries and uterus before carbon ion radiotherapy, resulting in the preservation of endocrine and reproductive function. CONCLUSION: The patient achieved optimal oncological response and delivered a healthy infant following the completion of cancer treatment.

Sexual health and contraception in the menopause journey.

Women may experience changes in sexuality across menopause, because at this step in life hormone deficiency interacts with several determinants in a bio-psycho-social perspective. Healthcare providers should inform women about menopause impact on sexuality and be proactive during consultation in disclosing sexual concerns that would require a targeted assessment. Sexual symptoms become more frequent as women age, but they do not always translate into sexual dysfunction diagnosis, for which distress is required. It is important to recognize conditions that may increase the risk of dysfunctional response to menopause challenges in order to promote sexual longevity through counselling and specific management. In this review, we report key elements for a comprehensive assessment of sexual health around menopause, with a focus on genitourinary syndrome of menopause (GSM) and hypoactive sexual desire disorder (HSDD), representing well identified clinical conditions affecting sexuality at midlife and beyond. We also address the issue of contraception across the menopausal transition, highlighting risks and benefits, and possible implications on sexual function.

The Role of Irisin throughout Women's Life Span.

Since its discovery, much attention has been drawn to irisin's potential role in metabolic and reproductive diseases. This narrative review summarizes and updates the possible role played by this fascinating molecule in different physiological (puberty and menopause) and pathological (polycystic ovary syndrome (PCOS), functional hypothalamic amenorrhea (FHA), endometriosis, and gestational diabetes) conditions that can affect women throughout their entire lives. Irisin appears to be an important factor for the hypothalamic-pituitary-gonadal axis activation, and appears to play a role in the timing of puberty onset. Serum irisin levels have been proposed as a biomarker for predicting the future development of gestational diabetes (GDM). Its role in PCOS is still controversial, although an "irisin resistance" mechanism has been hypothesized. In addition to its impact on metabolism, irisin also appears to influence bone health. Irisin levels are inversely correlated with the prevalence of fractures in postmenopausal women. Similar mechanisms have also been postulated in young women with FHA. In clinical settings, further controlled, prospective and randomized clinical trials are needed to investigate the casual relationship between irisin levels and the conditions described and, in turn, to establish the role of irisin as a prognostic/diagnostic biomarker or a therapeutic target.

Perimenstrual Asthma and Premenstrual Disorders in Adolescents with Asthma.

BACKGROUND: Asthma is a common chronic disease in pediatric patients, and perimenstrual asthma (PMA), refers to the worsening of asthma symptoms during the perimenstrual period, mainly reported in adult women. However, there is limited information regarding the exacerbation of symptoms in the presence of premenstrual disorders (PMDs) in adolescents. The aim of this pilot observational study was to investigate the frequency and potential association of PMA and PMDs in a clinical sample of adolescents with asthma. PATIENTS AND METHODS: The study included 50 adolescents (aged 12-18 years, mean 16.08 ± 2.35) with asthma and at least 2 years of gynecological age. The participants completed the Asthma Control Test (ACT) to assess asthma control (considered pathological if ACT score < 20) and the modified Premenstrual Symptoms Screening Tool for Adolescents (PSST-A) to evaluate PMDs. RESULTS: A total of 75.5% of adolescents reported PMA. The prevalence of premenstrual symptoms did not significantly differ between the PMA and no-PMA group. Among the study sample, 38.7% experienced symptoms indicative of moderate/severe premenstrual syndrome, and 8.1% exhibited symptoms of premenstrual dysphoric disorder. Compared with the no-PMA group, patients with PMA showed a significant impairment in daily and home activities (P = .03 and P = .02, respectively) and exhibited a difference in the frequency of asthma symptoms (P < .001) and medication use (P ≤ .01). CONCLUSION: Perimenstrual worsening of asthma symptoms may be common in adolescents with a severe form of asthma. Prospective data collection through menstrual diaries is necessary to further explore the association between PMA and PMDs. Identifying early risk factors for PMA could facilitate the development of preventive strategies and early interventions for adolescents with asthma.