The association of race, ethnicity, and socioeconomic status on the severity of menopause symptoms: a study of 68,864 women.

OBJECTIVE: This study aimed to evaluate if and how race, ethnicity, and socioeconomic status (SES) are associated with the severity of menopause symptoms in a large, diverse sample of women. METHODS: For this cross-sectional study conducted between March 24, 2019, and January 13, 2023, a total of 68,864 women were enrolled from the Evernow online telehealth platform. Participants underwent a clinical intake survey, which encompassed demographic information, detailed medical questionnaires, and a modified Menopause Rating Scale. The modified scale was adapted for ease of use online and is available in the supplementary material along with the full intake. Symptom severity was evaluated using a multivariate binomial generalized linear model, accounting for factors such as race, ethnicity, age, body mass index, smoking status, bilateral oophorectomy status, and SES. Odds ratios (OR) and CIs were calculated based on the linear regression coefficients. RESULTS: Of the participants, 67,867 (98.6%) were included in the analysis after excluding outliers and those with unknown oophorectomy status. The majority of respondents identified as White (77.4%), followed by Hispanic (9.0%), Black (6.7%), two or more races/ethnicities (4.4%), Asian (1.2%), Indigenous/First Nations (0.8%), Middle Eastern (0.3%), and South Asian (0.2%). Notably, individuals identifying as Black (hot flashes OR, 1.91; 97.5% CI, 1.75-2.09; P < 0.001), Hispanic (skin/hair changes OR, 1.58; 97.5% CI, 1.45-1.71; P < 0.001), Indigenous/First Nations (painful sex OR, 1.39; 97.5% CI, 1.19-2.75; P = 0.007), Middle Eastern (weight changes OR, 2.22; 97.5% CI, 1.25-4.37; P = 0.01), or with two or more races/ethnicities (skin/hair changes OR, 1.41; 97.5% CI, 1.26-1.58; P < 0.001) reported higher levels of symptom severity compared with their White counterparts. Conversely, Asian and South Asian participants reported lower symptom severity. Even after incorporating SES into the linear model, racial and ethnic groups with lower SES (Black, Hispanic, Indigenous, and multiple ethnicities) exhibited slight shifts in OR while maintaining high statistical significance (Black [hot flashes OR, 1.87; 97.5% CI, 1.72-2.04; P < 0.001], Hispanic [skin/hair changes OR, 1.54; 97.5% CI, 1.42-1.68; P < 0.001], Indigenous/First Nations [painful sex OR, 1.74; 97.5% CI, 1.17-2.70; P = 0.009], multiple ethnicities [skin/hair changes OR, 1.41; 97.5% CI, 1.26-1.58; P < 0.001]). CONCLUSIONS: Our study suggests that the relationship between race and ethnicity and the severity of menopause symptoms is not solely explained by differences in SES but is itself an independent factor. Understanding and addressing social, cultural, and economic factors are crucial to reduce disparities in menopausal symptoms.

Effects of Alcohol Administered With Flibanserin in Healthy Premenopausal Women: A Randomized, Double-Blind, Single-Dose Crossover Study.

INTRODUCTION: Flibanserin is approved in the United States and Canada for the treatment of hypoactive sexual desire disorder in premenopausal women. AIM: The purpose of this trial was to evaluate the safety of concomitant administration of flibanserin with alcohol. METHODS: In this single-center, randomized, double-blind, single-dose, crossover study, participants were randomly assigned to 1 of 12 sequences to receive each of 7 treatments: flibanserin 100 mg or placebo with ethanol 0.2 g/kg, 0.4 g/kg, or 0.6 g/kg, or flibanserin 100 mg only. Treatments were administered using a worst-case approach that included morning dosing and consumption of alcohol within 10 minutes. MAIN OUTCOME MEASURE: The primary end point was the proportion of participants who experienced dizziness, syncope, or hypotension. Safety end points included orthostatic vital signs. RESULTS: The study included 96 premenopausal women (mean age 31 ± 8 years). The incidence of dizziness for ethanol + flibanserin was 39.8% for ethanol 0.6 g/kg, 34.1% for 0.4 g/kg, and 27.4% for 0.2 g/kg compared with 31.1% for flibanserin without ethanol. Based on the available vital signs data, there was no effect of ethanol concentration on orthostatic blood pressure, vertigo, or hypotension; no instances of syncope were observed. The overall incidence of adverse events (AEs) was similar when flibanserin was administered alone (96.7%) or with ethanol (90.5-97.6%). CLINICAL IMPLICATIONS: Consumption of the tested amounts of alcohol (0.2-0.6 g/kg) does not have an additive effect on the AE profile of flibanserin 100 mg in healthy premenopausal women. STRENGTHS & LIMITATIONS: Strengths include the study population (premenopausal women, as indicated for flibanserin) and range of ethanol doses. Limitations include the morning dosing of study medication, which is inconsistent with the bedtime dosing recommended for flibanserin, and the method of handling missing vital sign measurements. CONCLUSION: Co-administration of flibanserin 100 mg with varying doses of ethanol resulted in few AEs of special interest, with no notable alcohol dose response. However, a significantly greater percentage of participants administered flibanserin with 0.6 g/kg and 0.4 g/kg of alcohol were characterized as "Participants in Whom Standing Blood Pressure Was Not Obtained" compared with participants administered flibanserin alone. Simon JA, Clayton AH, Parish SJ, et al. Effects of Alcohol Administered With Flibanserin in Healthy Premenopausal Women: A Randomized, Double-Blind, Single-Dose Crossover Study. J Sex Med 2020;17:83-93.

Early onset of action with a 17ß-estradiol, softgel, vaginal insert for treating vulvar and vaginal atrophy and moderate to severe dyspareunia.

OBJECTIVE: The softgel 17ß-estradiol (E2) vaginal inserts (4 and 10 µg; Imvexxy; TherapeuticsMD, Boca Raton, FL) are FDA approved for treating moderate to severe dyspareunia associated with postmenopausal vulvar and vaginal atrophy (VVA). The objective here was to determine responder rates at week 2 and whether week-2 findings predicted week-12 responders in the REJOICE trial. METHODS: Postmenopausal women received E2 vaginal inserts 4, 10, or 25 µg, or placebo for 12 weeks. Proportion of responders (having ≥2 of the following: vaginal superficial cells >5%, vaginal pH <5.0, or dyspareunia improvement of ≥1 category) were calculated. Odds ratios (ORs) for positive response at week 12 given a positive response at week 2 were determined in the efficacy evaluable (EE) population. RESULTS: The responder rate (in EE population [n = 695]) was 74% to 82% with E2 inserts versus 24% with placebo at week 2, and 72% to 80% versus 33% at week 12. Positive treatment responses were 9- to 14-fold higher with vaginal E2 than with placebo at week 2, and 5- to 8-fold higher at week 12. Response at week 2 predicted response at week 12 in the total population (OR 13.1; 95% CI, 8.8-19.7) and with active treatment only (OR 7.9; 95% CI, 4.7-13.2). CONCLUSIONS: A high percentage of postmenopausal women with moderate to severe dyspareunia responded with the E2 softgel vaginal insert at week 2, and a positive response at week 2 predicted a positive response at week 12.

Effects of Timing of Flibanserin Administration Relative to Alcohol Intake in Healthy Premenopausal Women: A Randomized, Double-Blind, Crossover Study.

INTRODUCTION: Flibanserin is approved in the United States and Canada for the treatment of acquired, generalized, hypoactive sexual desire disorder in premenopausal women. Sedation-related side effects are among the most prevalent adverse events. Although infrequent, hypotension and syncope remain safety concerns because of possible interaction of flibanserin with alcohol. AIM: To evaluate the impact of the timing of alcohol consumption on flibanserin safety and tolerability. METHODS: In this single-center, randomized, double-blind, placebo-controlled, 4-treatment crossover study, 64 healthy premenopausal women (mean age 32.5 ± 8.7 years; range 20‒52 years) received once-daily flibanserin 100 mg or placebo during each of two 10-day treatment periods. Study medication was administered on days 1-3 to achieve steady state. On days 4, 6, 8, and 10, after a standard breakfast, participants consumed 0.4 g/kg ethanol (approximately equivalent to two 5-oz glasses of wine) administered with orange juice 2, 4, or 6 hours before taking study medication or orange juice alone (no ethanol) 2 hours before taking study medication. OUTCOMES: The primary endpoint was percentage of participants experiencing syncope or orthostatic hypotension-associated adverse events requiring medical intervention. Secondary endpoints included the incidence of hypotension, the incidence of orthostatic hypotension, and rates of adverse events of special interest (syncope, orthostatic hypotension, dizziness, and somnolence). RESULTS: 1 participant experienced a primary endpoint event (syncope) during treatment with placebo taken 4 hours after ethanol consumption. Within each ethanol dose-timing treatment, there were no statistically significant differences for flibanserin compared with placebo. Rates of hypotension were 53.3-66.7% after flibanserin dosing and 57.4-63.3% after placebo dosing. Rates for orthostatic hypotension were 0.0-5.0% after flibanserin dosing and 1.7-6.6% after placebo dosing. CLINICAL IMPLICATIONS: Ethanol interaction with flibanserin was not observed in this study. STRENGTHS & LIMITATIONS: This study provides information regarding the use of flibanserin after the consumption of moderate amounts of ethanol (0.4 g/kg). However, daytime administration of flibanserin is not consistent with the drug's indicated bedtime dosing. CONCLUSION: Flibanserin, at steady state taken 2, 4, or 6 hours after 0.4 g/kg of ethanol intake did not increase the incidence of hypotension, orthostatic hypotension, or syncope compared with either flibanserin alone or ethanol alone. Simon JA, Clayton AH, Kingsberg SA, et al. Effects of Timing of Flibanserin Administration Relative to Alcohol Intake in Healthy Premenopausal Women: A Randomized, Double-Blind, Crossover Study. J Sex Med 2019;16:1779-1786.

Safety and Tolerability of Evening Ethanol Consumption and Bedtime Administration of Flibanserin in Healthy Premenopausal Female Subjects.

INTRODUCTION: Flibanserin, a treatment for hypoactive sexual desire disorder, carries warnings for increased risk of severe hypotension and syncope when used with alcohol. However, these warnings are not informed by studies that used flibanserin's recommended bedtime dosing because previous alcohol studies assessed flibanserin's safety during the day. AIM: The aim of this study was to assess the effects of ethanol in a real-world context in premenopausal women taking flibanserin at bedtime. METHODS: In a randomized, placebo-controlled, double-blind study, 24 healthy premenopausal women (mean age = 34.5 ± 9.9 years; mean body mass index = 25.2 ± 3.4 kg/m2) were dosed with flibanserin or placebo for 3 days to achieve steady-state plasma levels. In a clinical research unit, subjects (n = 22) were provided 2 units of wine (150 mL/unit; 12% ethanol content) or a nonalcoholic beverage with a standardized 3-course evening meal. Flibanserin 100 mg or placebo was administered at bedtime 2.5 hours after the end of the evening meal. On a separate day, subjects were provided the alternative beverage (± alcohol) with the same evening meal and dosed with the same treatment (flibanserin or placebo) at bedtime. After a 5-day washout period, subjects crossed over to the other treatment arm and the protocol was repeated. MAIN OUTCOME MEASURE: Adverse events (AEs) and vital signs were monitored. RESULTS: In the absence of ethanol, headaches and hypotension were the only AEs that occurred in ≥2 subjects after flibanserin dosing (placebo corrected rates were 17.4% and 8.7%, respectively). After ethanol consumption, the rate of hypotension after flibanserin dosing was no greater than with flibanserin or placebo after nonalcoholic beverage consumption. There were no instances of orthostatic hypotension or syncope and no serious AEs or AEs leading to study discontinuation. CONCLUSION: Flibanserin dosed at bedtime after moderate amounts of alcohol with an evening meal was well-tolerated with no evidence of clinically significant hypotension or syncope. Millheiser L, Clayton AH, Parish SJ, et al. Safety and Tolerability of Evening Ethanol Consumption and Bedtime Administration of Flibanserin in Healthy Premenopausal Female Subjects. Sex Med 2019;7:418-424.

Weight Loss in Women Taking Flibanserin for Hypoactive Sexual Desire Disorder (HSDD): Insights Into Potential Mechanisms.

INTRODUCTION: Flibanserin, a multifunctional serotonin receptor agonist and antagonist, is currently approved in the United States and Canada for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. A post hoc analysis of HSDD clinical trial data found that flibanserin treatment was associated with statistically significant weight loss relative to placebo, even though study patients were not selected for being overweight/obese and were provided no expectation for weight reduction or interventions intended to promote weight loss. AIM: To understand possible mechanisms by which flibanserin may produce weight loss. METHODS: A literature review was performed using Medline database for relevant publications on the mechanisms of action by which flibanserin may provide weight loss and the links between sexual function and weight management. MAIN OUTCOME MEASURES: Examination of (i) biopsychosocial factors regulating sexual desire, food intake, and weight regulation; (ii) clinical pharmacology of flibanserin; (iii) neurobiology of brain reward circuitry; and (iv) identification of possible mechanisms common to flibanserin and weight loss. RESULTS: Based on flibanserin clinical trial data, there was no consistent correlation between weight loss and improvement in sexual function, as assessed by HSDD outcome measures. Nausea, a common adverse event associated with flibanserin use, also did not appear to be a contributing factor to weight loss. Hypothetical links between flibanserin treatment and weight loss include modulation of peripheral 5-HT2A receptors and factors such as improved mood and improved sleep. CONCLUSION: Mechanisms of flibanserin-induced weight loss have not been well characterized but may involve indirect beneficial effects on peripheral 5-HT2A receptors and central regulation of mood and sleep. Future research may better elucidate the links between sexual function and weight management and the mechanism(s) by which flibanserin use may result in weight loss. Simon JA, Kingsberg SA, Goldstein I, et al. Weight Loss in Women Taking Flibanserin for Hypoactive Sexual Desire Disorder (HSDD): Insights into Potential Mechanisms. Sex Med Rev 2019;7:575-586.

Flibanserin for Premenopausal Hypoactive Sexual Desire Disorder: Pooled Analysis of Clinical Trials.

Background: Flibanserin, a 5-hydroxytryptamine 5-HT1A agonist and 5-HT2A antagonist, is indicated for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. This post hoc analysis assessed pooled efficacy and safety data for flibanserin in premenopausal women with HSDD. Materials and Methods: Data for flibanserin 100 mg once daily at bedtime (qhs) and placebo were pooled from three pivotal 24-week, randomized, placebo-controlled, multicenter studies (VIOLET, DAISY, and BEGONIA) of premenopausal women with HSDD. Pooled efficacy endpoints included the change from baseline to study end (i.e., 24 weeks) in the number of satisfying sexual events (SSEs) over 28 days, the Female Sexual Function Index desire domain (FSFI-d) score, and the Female Sexual Distress Scale-Revised Item 13 (FSDS-R-13) score. Results: The analysis included 2465 women (flibanserin, n = 1227; placebo, n = 1238) with a mean age of 36 years and a mean HSDD duration of 56.5 months. The mean ± standard error (SE) change from baseline to study end in SSEs over 28 days for flibanserin versus placebo was 2.1 ± 0.14 versus 1.2 ± 0.11, respectively (p < 0.0001). The least-squares mean ± SE changes from baseline to study end in FSFI desire domain score and FSDS-R-13 score were also significantly greater for flibanserin versus placebo (FSFI desire domain: 0.9 ± 0.04 vs. 0.6 ± 0.04, p < 0.0001; FSDS-R-13: -0.9 ± 0.04 vs. -0.6 ± 0.04, p < 0.0001). Patients in the flibanserin group generally had significantly greater improvements, compared with placebo, in SSEs, FSFI-d score, and FSDS-R-13 in subgroup analyses based on selected demographic and baseline clinical characteristics. Adverse events occurring in ≥10% of patients included dizziness and somnolence. Conclusions: This pooled analysis of three pivotal trials demonstrated that flibanserin 100 mg qhs was well tolerated, improved sexual desire, and reduced sexual distress associated with HSDD in premenopausal women, and these improvements were generally consistent across various subgroups based on demographic and baseline characteristics.

The impact of Fiera, a women's personal care device, on genital engorgement as measured by thermography: a proof-of-principle study.

OBJECTIVE: To determine the degree of vasoengorgement of the external genitalia caused by Fiera, a personal care device developed specifically to increase sexual arousal and interest. Time to onset of self-reported genital sexual arousal and development of responsive sexual desire were also measured. METHODS: This nonblinded, prospective cohort, single-site study was conducted in women without sexual dysfunction between the ages of 18 and 70. Each participant underwent a single-visit procedure that established a baseline temperature of the external genitalia, followed by 15 minutes of Fiera use. A post-Fiera temperature assessment lasting 10 minutes was performed. Subjective measures assessed the development of genital arousal and responsive desire as a result of Fiera use. RESULTS: Fourteen premenopausal and 12 postmenopausal participants completed the study. Mean time to reach genital arousal was 5.2 + 4.2 minutes in the premenopausal group, and 4.5 + 4.3 minutes in the postmenopausal group. Statistically significant increases in the temperature of the clitoris and vestibule were demonstrated in both groups up to 10 minutes after removal of Fiera. At the labia, temperature increase was significant up to 8 minutes in the premenopausal group and up to 2 minutes in the postmenopausal group. All of the participants experienced responsive sexual desire as a result of Fiera. CONCLUSIONS: Use of Fiera produced statistically significant increases in the temperature of the external genitalia, markers of vasoengorgement, in both the premenopausal and postmenopausal participants. The onset of genital sexual arousal was rapid in both groups, and responsive sexual desire was experienced by all of the participants.

Sexual health and religion: a primer for the sexual health clinician (CME).

INTRODUCTION: Sexual health is an integral part of the multifaceted human experience that is driven both by biological factors and psychological facets. Religion may provide a moral code of conduct or a sexual compass as to sexual norms and behaviors. AIM: The aim of this study was to summarize the integration of sexuality and religion. METHOD: A review of published literature and religious texts was conducted. RESULTS: The integration of religion with country or state politics and laws is a complicated dilemma and will not be discussed in the scope of this article. The extent to which an individual incorporates their religious doctrine into their sexual life is a personal and individualized choice. The sexual medicine health professional will likely encounter a diverse patient population of distinct religious backgrounds, and a primer on religion and sexuality is a much needed adjunctive tool for the clinician. CONCLUSION: Because religion can influence sexuality and dictate, in part, the behavioral and medical treatments for sexual complaints, the clinician should be familiar with religious guidelines regarding sexuality, and treatment should be customized and individualized. Failure to do so can impact compliance with the therapeutic interventions. Religious awareness also solidifies the therapeutic alliance between clinician and patient as it demonstrates respect and acknowledgment for patient's beliefs and autonomy.

Fertility issues in cancer survivorship.

Breakthroughs in cancer diagnosis and treatment have led to dramatic improvements in survival and the need to focus on survivorship issues. Chemotherapy and radiotherapy can be gonadotoxic, resulting in impaired fertility. Techniques to help cancer survivors reproduce have been improving over the past decade. Discussion of the changes to a patient's reproductive health after cancer treatment is essential to providing comprehensive quality care. The purpose of this review is to aid in pre- and posttreatment counseling, focusing on fertility preservation and other strategies that may mitigate risks to the patient's reproductive, sexual, and overall health.

Sexual health issues in women with cancer.

INTRODUCTION: Sexual health issues for women who have cancer are an important and under-diagnosed and under-treated survivorship issue. Survivorship begins at the time a cancer is detected and addresses health-care issues beyond diagnosis and acute treatment. This includes improving access to care and quality-of-life considerations, as well as dealing with the late effects of treatment. Difficulties with sexual function are one of the more common late effects in women. AIM: This article attempted to characterize the etiology, prevalence, and treatment for sexual health concerns for women with gynecological cancer. METHODS: A systematic survey of currently available relevant literature published in English was conducted. RESULTS: The issue of sexual health for women with cancer is a prevalent medical concern that is rarely addressed in clinical practice. The development of sexual morbidity in the female cancer survivor is a multifactorial problem incorporating psychological, physiologic, and sociological elements. Treatments such as chemotherapy, radiation therapy, surgery, and hormonal manipulation appear to have the greatest influence on the development of sexual consequences. Sexual complaints include but are not limited to changes in sexual desire, arousal, and orgasmic intensity and latency. Many women suffer from debilitating vaginal dryness and painful intercourse. CONCLUSIONS: Many of the sexual health issues experienced by cancer survivors can be addressed in clinical practice. A multimodal treatment paradigm is necessary to effectively treat these sexual complaints in this special patient population.

Radiofrequency treatment of vaginal laxity after vaginal delivery: nonsurgical vaginal tightening.

INTRODUCTION: All women who have given birth vaginally experience stretching of their vaginal tissue. Long-term physical and psychological consequences may occur, including loss of sensation and sexual dissatisfaction. One significant issue is the laxity of the vaginal introitus. AIM: To evaluate safety and tolerability of nonsurgical radiofrequency (RF) thermal therapy for treatment of laxity of the vaginal introitus after vaginal delivery. We also explored the utility of self-report questionnaires in assessing subjective effectiveness of this device. METHODS: Pilot study to treat 24 women (25-44 years) once using reverse gradient RF energy (75-90 joules/cm(2) ), delivered through the vaginal mucosa. Post-treatment assessments were at 10 days, 1, 3, and 6 months. MAIN OUTCOME MEASURES: Pelvic examinations and adverse event reports to assess safety. The author modified Female Sexual Function Index (mv-FSFI) and Female Sexual Distress Scale-Revised (FSDS-R), Vaginal Laxity and Sexual Satisfaction Questionnaires (designed for this study) to evaluate both safety and effectiveness, and the Global Response Assessment to assess treatment responses. RESULTS: No adverse events were reported; no topical anesthetics were required. Self-reported vaginal tightness improved in 67% of subjects at one month post-treatment; in 87% at 6 months (P<0.001). Mean sexual function scores improved: mv-FSFI total score before treatment was 27.6 ± 3.6, increasing to 32.0 ± 3.0 at 6 months (P < 0.001); FSDS-R score before treatment was 13.6 ± 8.7, declining to 4.3 ± 5.0 at month 6 post-treatment (P < 0.001). Twelve of 24 women who expressed diminished sexual satisfaction following their delivery; all reported sustained improvements on SSQ at 6 months after treatment (P = 0.002). CONCLUSION: The RF treatment was well tolerated and showed an excellent 6-month safety profile in this pilot study. Responses to the questionnaires suggest subjective improvement in self-reported vaginal tightness, sexual function and decreased sexual distress. These findings warrant further study.

Is infertility a risk factor for female sexual dysfunction? A case-control study.

OBJECTIVE: To determine the impact of infertility on female sexual function. DESIGN: A case-control study. SETTING: Academic infertility and gynecology practices. PATIENT(S): One hundred nineteen women with infertility and 99 healthy female controls without infertility between the ages of 18 and 45 years were included in this study. INTERVENTION(S): Anonymous survey and Female Sexual Function Index. MAIN OUTCOME MEASURE(S): Female Sexual Function Index scores, frequency of sexual intercourse and masturbation, and sex-life satisfaction. RESULT(S): Twenty-five percent of our control group had Female Sexual Function Index scores that put them at risk for sexual dysfunction (<26.55), whereas 40% of our patients with infertility met this criterion. Compared with the control group, the patients with infertility had significantly lower scores in the desire and arousal domains and lower frequency of intercourse and masturbation. The patients with infertility retrospectively reported a sex-life satisfaction score that was similar to that of the controls before their diagnosis, whereas their current sex-life satisfaction scores were significantly lower than those of the controls. CONCLUSION(S): Women with a diagnosis of infertility were found to be at higher risk for sexual dysfunction on the basis of their Female Sexual Function Index scores compared with women without infertility. The interaction of sexual function and infertility is complex and deserves further study.

Severe vaginal pain caused by a neuroma in the rectovaginal septum after posterior colporrhaphy.

BACKGROUND: Traumatic vaginal neuromas are a rarely documented finding in the setting of vaginal pain after posterior colporrhaphy. They arise as a result of trauma or surgery and are often mistaken for scar tissue. CASE: After a total vaginal hysterectomy and posterior colporrhaphy, a 32-year-old woman presented with debilitating vaginal pain, presumed to be secondary to scar tissue formation. Excision of the tissue from the rectovaginal septum revealed a traumatic neuroma. After the removal of the neuroma, the patient's vaginal pain resolved. CONCLUSION: Traumatic neuromas may be a cause of significant point tenderness and thickened tissue after vaginal surgery or repair of obstetric lacerations. If conservative treatment methods have failed, surgical excision of the neuroma can be considered.