Role of flibanserin in managing hypoactive sexual desire disorder in women: A systematic review and meta-analysis.

BACKGROUND: Flibanserin, approved for the treatment of hypoactive sexual desire disorder (HSDD) in females, has demonstrated diverse therapeutic and adverse effect (AE) prospects in the extant randomized controlled trials (RCTs). This meta-analysis aimed to characterize the outcomes of flibanserin use in these patients comprehensively. METHODS: RCTs involving women with HSDD receiving flibanserin in the intervention arm and placebo in the control arm were sought after throughout the electronic databases. The primary outcomes were the changes from baseline in satisfying sexual events (SSE) per month and sexual desire score per month measured using an electronic diary (eDiary). RESULTS: From 478 initially screened articles, data from 8 RCTs involving 7906 women with HSDD were analyzed. In premenopausal women, flibanserin 100 mg was superior to placebo in improving the number of SSE per month (mean difference, MD 0.69, 95% CI [0.39, 0.99]), eDiary sexual desire score (MD 1.71, 95% CI [0.43, 2.98]), Female Sexual Function Index (FSFI) desire domain (FSFI-d) score (MD 0.30, 95% CI [0.29, 0.31]), FSFI total score (MD 2.51, 95% CI [1.47, 3.55]), Female Sexual Distress Scale-Revised (FSDS-R) Item 13 score (MD -0.30, 95% CI [-0.31, -0.29]), and FSDS-R total score (MD -3.30, 95% CI [-3.37, -3.23]). Compared to placebo, a higher number of premenopausal women using flibanserin 100 mg achieved improvements in the Patient's Global Impression of Improvement score (OR 1.93, 95% CI [1.58, 2.36], P < .00001) and responded positively at Patient Benefit Evaluation (PBE) (odds ratio, OR 1.76, 95% CI [1.34, 2.31], P < .0001). Postmenopausal women receiving flibanserin 100 mg also benefited in terms of the number of SSE per month, FSFI-d and total scores, FSDS-R Item 13 and total scores, and PBE response. Although flibanserin use was associated with higher risks of dizziness, fatigue, nausea, somnolence, and insomnia, these adverse events were mild in nature; the serious AEs and severe AEs were comparable between the flibanserin and placebo groups. CONCLUSION: While flibanserin has demonstrated efficacy in the treatment of HSDD in both pre- and postmenopausal women, its therapeutic advantages may be overshadowed by the higher likelihood of AEs.

Systemic testosterone for the treatment of female sexual interest and arousal disorder (FSIAD) in the postmenopause.

INTRODUCTION: Female sexual interest and arousal disorder (FSIAD) is the most prevalent female sexual dysfunction in the postmenopause. OBJECTIVE: The aim of this review is to provide a summary of the currently available evidence on the use of testosterone in the treatment of FSIAD in postmenopausal women. METHODS: A narrative review on the topic was performed. Only randomized controlled trials (RCTs) and systematic reviews and meta-analysis were considered. 123 articles were screened, 105 of them assessed for eligibility, and finally 9 were included in qualitative synthesis following the PRISMA declaration. RESULTS: Current evidence recommends, with moderate therapeutic benefit, the use of systemic transdermal testosterone within the premenopausal physiological range in postmenopausal women with Hypoactive Sexual Desire Disorder (HSDD), the previous entity for low desire dysfunction, not primarily related to modifiable factors or comorbidities such as relationship or mental health problems. The available evidence is based on studies with heterogeneity on their design (different testosterone doses, routes of administration, testosterone use in combination and alone, sexual instruments of measurement). There is no data indicating severe short-term adverse effects, although long-term safety data is lacking. CONCLUSIONS: Despite having testosterone as a valuable tool, therapeutic strategies are lacking in the pharmacological field of HSDD/FSIAD. Neuroimaging studies could provide valuable information regarding the sexual desire substrate and suggest the potential application of already approved drugs for women with a good safety profile. The use of validated instruments for HSDD in postmenopausal women, considering the level of distress, is necessary to be able to draw robust conclusions on the evaluated treatments.

NRG-CC004 ancillary data study-exploring the effect of bupropion on sexual desire in female cancer survivors with and without vulvovaginal symptoms.

BACKGROUND: Female cancer survivors often experience estrogen-deprivation symptoms, which may lead to decreases in sexual desire, vulvovaginal health (lubrication, dryness, discomfort), and sexual satisfaction. Interventions are needed to address these concerns. AIM: The objective of this secondary analysis was to determine if women with higher (better) scores on the Female Sexual Function Index (FSFI) lubrication and pain subscales reported higher desire scores based on treatment with bupropion vs placebo. METHODS: Participants were part of NRG Oncology's NRG-CC004 (NCT03180294), a randomized placebo-controlled clinical trial evaluating bupropion (150 vs 300 mg) to improve sexual desire in survivors of breast or gynecologic cancer. All participants with baseline data from the FSFI lubrication, pain, and desire subscales with 5- and/or 9-week data were analyzed. The FSFI subscale scores were correlated using Spearman correlation coefficients. Logistic regression was used to determine associations between FSFI desire and other FSFI subscales while accounting for treatment arm and other covariates. OUTCOMES: The primary outcome of NRG Oncology's NRG-CC004 (NCT03180294) randomized phase II dose-finding trial was change from baseline to 9 weeks on the FSFI desire subscale score. Similar to the parent study, the primary outcome for this ancillary data study was the FSFI desire subscale score at 5 and 9 weeks. RESULTS: Overall, 230 participants completed the FSFI at baseline and 189 at 9 weeks. The strongest correlations were between lubrication and pain at baseline (all participants, rho = 0.77; bupropion arms, rho = 0.82), week 5 (all participants, rho = 0.71; bupropion arms, rho = 0.68), and week 9 (all participants, rho = 0.75; bupropion arms, rho = 0.78), and the weakest correlations were between desire and pain. In patients in the treatment arms there were no interactions between lubrication or pain.The impact of various covariates on the FSFI score for desire at 9 weeks demonstrated that participants of non-White race (odds ratio [OR], 0.42; 95% CI, 0.21-0.81; P = .010), with a high lubrication score (OR, 0.36; 95% CI, 0.21-0.61; P = .0002), with a high pain score (less pain) (OR, 0.50; 95% CI, 0.29-0.87; P = .014), or with prior pelvic surgery (OR, 0.38; 95% CI, 0.23-0.63; P = .0002) had lower odds of having low desire. CLINICAL IMPLICATIONS: Acute estrogen-deprivation symptoms should be addressed prior to sexual desire intervention. STRENGTHS AND LIMITATIONS: This secondary analysis was not powered to examine all variables. CONCLUSION: Lubrication and pain were predictors of low desire. Therefore, vulvovaginal atrophy and associated genitourinary symptoms of menopause such as vaginal dryness and dyspareunia should be addressed prior to or in parallel with interventions for sexual desire.

Sexual Desire and Pharmacologic Management.

Female sexual desire is a complex interplay of neurotransmitters and hormones. Diagnosis is based on clinical features and sexual distress. Treatments that affect neurotransmitters and hormones that may be out of balance can help improve sexual desire in women with hypoactive sexual desire disorder.

Ovulatory cycle shifts in human motivational prioritisation of sex and food.

Previous research on the endogenous effects of ovarian hormones on motivational states in women has focused on sexual motivation. The Motivational Priority Shifts Hypothesis has a broader scope. It predicts a shift from somatic to reproductive motivation when fertile. In a highly powered preregistered online diary study across 40 days, we tested whether 390 women report such an ovulatory shift in sexual and eating motivation and behaviour. We compared 209 naturally cycling women to 181 women taking hormonal contraceptives (HC) to rule out non-ovulatory changes across the cycle as confounders. We found robust ovulatory decreases in food intake and increases in general sexual desire, in-pair sexual desire and initiation of dyadic sexual behaviour. Extra-pair sexual desire increased mid-cycle, but the effect did not differ significantly in HC women, questioning an ovulatory effect. Descriptively, solitary sexual desire and behaviour, dyadic sexual behaviour, appetite, and satiety showed expected mid-cycle changes that were diminished in HC women, but these failed to reach our strict preregistered significance level. Our results provide insight into current theoretical debates about ovulatory cycle shifts while calling for future research to determine motivational mechanisms behind ovulatory changes in food intake and considering romantic partners' motivational states to explain the occurrence of dyadic sexual behaviour.

Longitudinal changes in sexual desire and attraction among women who started using the Natural Cycles app.

Many women experience sexual side effects, such as decreased libido, when taking hormonal contraceptives (HCs). However, little is known about the extent to which libido recovers after discontinuing HCs, nor about the timeframe in which recovery is expected to occur. Given that HCs suppress the activities of multiple endogenous hormones that regulate both the ovulatory cycle and women's sexual function, resumption of cycles should predict libido recovery. Here, using a combination of repeated and retrospective measures, we examined changes in sexual desire and partner attraction (among partnered women) across a three-month period in a sample of Natural Cycles users (Survey 1: n = 1596; Survey 2: n = 550) who recently discontinued HCs. We also tested whether changes in these outcomes coincided with resumption of the ovulatory cycle and whether they were associated with additional factors related to HC use (e.g., duration of HC use) or relationship characteristics (e.g., relationship length). Results revealed that both sexual desire and partner attraction, on average, increased across three months after beginning to use Natural Cycles. While the prediction that changes in sexual desire would co-occur with cycle resumption was supported, there was also evidence that libido continued to increase even after cycles resumed. Together, these results offer new insights into relationships between HC discontinuation and women's sexual psychology and lay the groundwork for future research exploring the mechanisms underlying these effects.

Correlation of sexual desire with sexual hormone binding globulin and free androgen index in women using combined contraceptives.

PURPOSE: To correlate the sexual desire levels with sexual hormone binding globulin and free androgen index in women taking different types of hormonal contraceptives (HCs) containing ethinylestradiol (EE), oestradiol valerate (E2V), 17ß-oestradiol (E2), or estetrol (E4), combined or in phasic formulation with different progestogens having antiandrogenic properties. METHODS: Three hundred and sixty-seven women (age range 18-46) participated in the study. SHBG and total testosterone (TT) were measured, and the Free Androgen Index (FAI) was calculated. The Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale (FSDS) questionnaires were used to assess sexual function and distress, respectively. RESULTS: The highest SHBG values and the lowest FAIs were obtained of women on HCs containing EE than those of women on HCs containing E2V/17ß E2 or E4 (p < 0.001). Desire scores and FSFI total scores were lower in women on HCs with EE than in those using HCs containing E2V, 17ß E2, or E4 (p ≤ 0.001). The women who were on HCs containing EE reported FSDS levels higher than those containing all the other types of oestrogen. Finally, sexual desire and FSFI total scores had a negative correlation with the SHBG values and a positive correlation with FAI percentage (p ≤ 0.0001). CONCLUSIONS: A minority of women using HCs with EE might experience a decreased sexual desire. This was not observed in women on HCs containing E2V, 17 E2, or E4. To avoid HC discontinuation, due to sexual desire reduction, HCs having minor antiandrogenic effects could be taken into consideration.

Combined estrogen-progestin oral contraceptives and female sexuality: an updated review.

INTRODUCTION: Sexual side effects of combined oral contraceptives (COCs) have not been fully understood, but increasing evidence prompts broader risk/benefit evaluation and merits inclusion in counseling on contraceptive options. OBJECTIVES: The study sought to explore the impact of combined estrogens-progestin oral contraceptives on components of female sexuality, including sexual desire, anatomic genitourinary changes, lubrication, orgasm, provoked vestibulodynia, well-being, body image, partner preference, and relationship stability. METHODS: A literature review was performed between April 2023 and January 2024 exploring the association between combined oral contraceptive pills and sexual health. RESULTS: Although COCs decrease free testosterone, it is unclear if COCs affect sexual function, including desire. Antiandrogenic COCs do seem to have a negative effect on sexual arousal, lubrication, and orgasm. Provoked vestibulodynia may be related to early onset of COC use, low-estrogen pills, and antiandrogenic progestins. Emotional and sexual side effects are strong predictors of COC discontinuation. Longitudinal data indicate that using COCs when meeting and selecting a partner has implications on sexual satisfaction and relationship length. Analysis of data is complicated by various doses and forms of estrogen and progestin in COCs, which have changed over time. CONCLUSION: Lack of randomized placebo-controlled studies and heterogenicity in study design hampers generalized statements about the effects of COCs on sexual function. Despite these challenges, consideration of sexual dysfunction when presenting and prescribing hormonal contraception is essential for informed consent, shared decision making, and ensuring reliable contraceptive choices.

O impacto do uso de métodos contraceptivos orais na função sexual de mulheres em idade reprodutiva / The impact of the use of oral contraceptive methods on the sexual function of women of reproductive age

Objetivo: Investigar o impacto dos contraceptivos orais hormonais na função sexual de mulheres. Métodos: Estudo transversal realizado por meio do questionário traduzido e validado "Índice da Função Sexual Feminina", capaz de estimar o risco de disfunção sexual feminina. Dados sociodemográficos, ginecológicos, medicamentosos e outros foram avaliados e correlacionados estatisticamente a esse escore, estimando possíveis causas da disfunção sexual, com destaque para o uso de anticoncepcional oral. O estudo foi baseado em uma amostragem por conveniência, incluindo mulheres > 18 anos em idade reprodutiva, de 04/01/2021 a 04/01/2022, obedecendo aos critérios de inclusão e exclusão. Resultados: Participaram deste estudo 105 mulheres com média e desvio-padrão de idade de 23,4 ± 3,8 anos, predominantemente heterossexuais (84,0%) e bissexuais (13,2%). A maioria delas (93,4%) utiliza métodos contraceptivos, sendo esses anticoncepcional oral (45,3%), DIU hormonal (19,8%) e camisinha (17,0%). A composição hormonal mais utilizada foi levonorgestrel (26,4%) e etinilestradiol (25,5%). Oitenta por cento das mulheres são sexualmente ativas, 69,3% delas têm parceria fixa, 42,5% tinham relações quase sempre e 33,0% referiam que as relações sexuais eram sempre satisfatórias. Houve boa adequação da amostra (0,865) e significância estatística (p < 0,0001). Utilizar ou não método contraceptivo apresentou diferença nos domínios desejo, satisfação e dor. Contudo, as questões do histórico sexual foram as que mais apresentaram relevância estatística em relação aos domínios. Conclusão: Apesar de outros estudos serem necessários para provar a hipótese de que os contraceptivos orais têm impacto negativo na função sexual feminina, é clara a importância de os profissionais de saúde já estarem cientes dessa possibilidade e saberem como abordá-la.

Objective: To investigate the impact of hormonal oral contraceptives on women's sexual function. Methods: Cross-sectional study carried out using the translated and validated questionnaire "Index of Female Sexual Function", capable of estimating the risk of female sexual dysfunction. Sociodemographic, gynecological, medication and other data were evaluated and statistically correlated to this score, estimating possible causes of sexual dysfunction, with emphasis on the use of oral contraceptives. The study was based on a convenience sample, including women > 18 years of reproductive age, from 01/04/2021 to 01/04/2022, following inclusion and exclusion criteria. Results: The study included 105 women with a mean and standard deviation of (23.4 ± 3.8) years old, predominantly heterosexual (84.0%) and bisexual (13.2%). Most of them (93.4%) use contraceptive methods, these being (45.3%) oral contraceptives, (19.8%) hormonal IUDs and (17.0%) condoms. The most used hormonal composition was levonorgestrel (26.4%) and ethinylestradiol (25.5%). Eighty percent of the women are sexually active, 69.3% of them have a steady partner, 42.5% almost always had sex and 33.0% said that sex was always satisfactory. There was good sample adequacy (0.865) and statistical significance (p < 0.0001). Using or not using a contraceptive method showed a difference in the desire, satisfaction and pain domains. However, sexual history questions were the ones that showed the most statistical relevance in relation to the domains. Conclusion: Although further studies are needed to prove the hypothesis that oral contraceptives have a negative impact on female sexual function, it is clear that health professionals are already aware of this possibility and know how to approach it.

Glutamine restores testicular glutathione-dependent antioxidant defense and upregulates NO/cGMP signaling in sleep deprivation-induced reproductive dysfunction in rats.

Oxidative stress has been linked with sleep deprivation (SD)-induced pathological conditions and reproductive dysfunction. On the other hand, glutamine has been established to have antioxidant property. However, the impact of SD, with or without glutamine, on male reproductive function is yet to be elucidated. Thus, this study was designed to investigate the role of SD, with or without glutamine, on male reproductive function and possible associated mechanisms. Ten-week old male Wistar rats weighing 175.6 g± 0.42 were randomly assigned into vehicle that received per os (p.o.) distilled water, glutamine (1 g/kg; po), SD, and SD + glutamine that received treatments as glutamine and SD. Treatment/exposure lasted for 72 h. The results showed that SD led to reduced body weight, seminiferous luminal and epididymal sperm density, low sperm quality, increased testicular and epididymal malondialdehyde, uric acid, DNA fragmentation, and testicular injury markers. In addition, SD caused a reduction in reduced glutathione level and activities of superoxide dismutase, catalase, glucose-6-phosphate dehydrogenase, glutathione peroxidase, and glutathione-S-transferase. Also, SD increased tumor necrotic factor-α, interleukin-1ß, and nuclear factor-kappa B levels. Furthermore SD led to impaired libido and erectile dysfunction, and suppression of circulatory nitric oxide, gonadotropins and testosterone, and penile cGMP. However, glutamine attenuated the effects induced by SD. Taken together, the findings of this study demonstrate that SD induces reproductive dysfunction via glutathione-dependent defense depletion and down-regulation of NO/cGMP signaling, which was abolished by glutamine supplementation.

Men Converting from Clomiphene Citrate to Natesto with a Desire to Maintain Spermatogenesis Should Be Followed Closely.

OBJECTIVE: To report a case of a testosterone deficient man desiring maintenance of spermatogenesis converting from clomiphene citrate (CC) to Natesto, who had a decrease in gonadotropins and semen parameter values after making this medication change. The data on men maintaining gonadotropins and semen parameter values after converting from CC to Natesto is also reported. METHODS: A retrospective chart review was performed. Baseline hormones prior to treatment, and again on CC and Natesto, as well as semen parameters on CC and on Natesto were assessed. RESULTS: A 32-year-old testosterone deficient man desiring to maintain future fertility potential who had a poor symptomatic response to CC despite an adequate serum testosterone response was converted to Natesto 11 mg twice daily. His gonadotropins diminished as did his semen parameter values but with dose titration of Natesto to 11 mg in the morning and 5.5 mg in the evening he had normalization of gonadotropins and a rise in semen parameter values back towards his values on CC with a continued satisfactory symptomatic response. The remainder of the 49 men to date converting from CC to Natesto revealed stability in gonadotropins and semen parameter values. CONCLUSION: Testosterone deficient men interested in maintaining spermatogenesis who convert from CC to Natesto seeking a more robust symptomatic response should be followed closely with repeat serum gonadotropins and semen parameters to confirm that spermatogenesis is not being suppressed. Dose titration of Natesto may be effective at optimizing gonadotropins, semen parameter values, testosterone levels, and symptomatic response to treatment.

Benzodiazepines related sexual dysfunctions: A critical review on pharmacology and mechanism of action / Disfunciones sexuales relacionadas con las benzodiazepinas: una revisión crítica sobre farmacología y mecanismo de acción

INTRODUCTION: Normal sexual functioning of both men and women, being a very complex process, is affected by numerous issues besides aging. Many factors affect the sexual function and lifestyle of the young population. In this article, we tried to review the literature to update the knowledge on benzodiazepine-related (BZD) sexual dysfunction (SD) and involved mechanisms of actions based on animal and human studies. METHODS: Different standard websites such as PubMed were used to review the literature and keywords including benzodiazepines, sexual dysfunction, gammaaminobutyric acid A (GABAA) receptor and erectile dysfunction were used. RESULTS: SD is one of the most common disorders in males and females which has recently been demonstrated to be associated with psychotropic medications such as antihypertensive agents, tranquilizers, antihistamines, appetite suppressants, antidepressants and anxiolytics. BZDs are among the most common psychotropic agents worldwide. SD including decreased libido, erectile dysfunction (ED) and other undesired sexual urges were observed in the patients receiving BZDs. DISCUSSION: The mechanisms of action of BZDs to induce SD mainly relate to enhanced GABAA receptor function which reduces penile erection

INTRODUCCIÓN: El funcionamiento sexual normal de los varones y las mujeres, al ser un proceso muy complejo, se ve afectado por numerosos problemas, además del envejecimiento. Muchos factores afectan a la función sexual y al estilo de vida de la población joven. En este artículo intentamos revisar la literatura para actualizar el conocimiento sobre las disfunciones sexuales (SD, por sus siglas en inglés) relacionadas con benzodiacepinas (BZD) y los mecanismos de acción involucrados en estudios con animales y humanos. MÉTODOS: Se utilizaron diferentes sitios web estándar, como PubMed, para revisar la literatura y las palabras clave que incluyen BZD, disfunciones sexuales, ácido gamma-aminobutírico A y disfunción eréctil. RESULTADOS: Las SD son uno de los trastornos más comunes en los varones y las mujeres, ya que recientemente se ha demostrado que están asociados a medicamentos psicotrópicos como agentes antihipertensivos, tranquilizantes, antihistamínicos, supresores del apetito, antidepresivos y ansiolíticos. Las BZD son uno de los agentes psicotrópicos más comunes en todo el mundo. Las SD que incluían disminución de la libido, la disfunción eréctil (DE) y otros impulsos sexuales no deseados, se observaron en los pacientes que recibieron BZD. DISCUSIÓN: Los mecanismos de acción de las BZD para inducir SD se relacionan principalmente con la función mejorada del receptor de ácido gamma-aminobutírico A (GABAA) que reduce la erección del pene

Tribulus terrestris and female reproductive system health: A comprehensive review.

BACKGROUND: Tribulus terrestris L. (T. terrestris) positive performance on the male sexual system has been confirmed, but little is known about its effects on the female reproductive system. PURPOSE: This review discussed in detail the beneficial impact of T. terrestris and its secondary metabolites on the female reproductive system. STUDY DESIGN AND METHODS: In this review, the scientific Databases of Science direct, Pubmed, Web of Science, Google, Google Scholar, Researchgate, EMBASE, Scientific Information (SID), and Elsevier were searched profoundly. Studies about the pharmacological activities of T. terrestris on the female reproductive system in each aspect of investigations: human, in vivo, and in vitro studies, in the period from 1998 to 2020 were admitted. Our study was not limited by the language of publications. RESULTS: 23 articles about the effects of T. terrestris on the female reproductive system were found. These studies approved the T. terrestris efficacy on improvements in histological features of the ovary and uterus of polycystic ovary syndrome patients as well as the well-working of normal ovaries, enhancements in the sexual desire of postmenopausal syndrome, improve ovarian and breast cancers. CONCLUSION: These studies showed that the positive effect of T. terrestris on the female reproductive system was due to the presence of a secondary metabolite called protodioscin; a steroidal saponin compound, as the dominant active component of this plant.

Do high-dose progestins impair sexual function in women treated for endometriosis? A prospective observational longitudinal study.

INTRODUCTION: High-dose progestins are used as an effective therapy for painful symptoms of endometriosis but their impact on sexual function has been poorly studied. The study aims to assess the impact of high-dose progestin on sexual function among women treated for endometriosis. MATERIAL AND METHODS: In this bicenter prospective observational study, women with endometriosis who received medical or surgical treatment for endometriosis and who were sexually active were included. They completed the Sexual Activity Questionnaire (SAQ, a validated tool) before (T0) and 12 months after (T1) endometriosis treatment. We classified patients into two groups according to whether they were using high-dose progestins at T1: a high-dose progestin group and a control group. The main outcome was sexual function measured by the SAQ score (from 0 to 30) at T1. The secondary outcomes were each individual SAQ item, the dyspareunia 100-mm visual analog scale (VAS) and the quality of life assessed with EuroQoL Group 5D Index (EQ-5D) at T1. We also assessed the change in dyspareunia VAS and quality of life between T0 and T1. The Ethics Committee of Ile-de-France (Act 2004-806, 9 August 2004) approved the study. RESULTS: Among 214 women included, 25 (12%) were exposed to high-dose progestins at T1. The SAQ score of women exposed to high-dose progestins was significantly lower compared with the control group, with or without adjustment for covariates (15.5 ± 6.3 vs 18.3 ± 6.2, P = .03, adjusted effect size -0.44 [95% CI -0.86 to -0.02], P = .04). High-dose progestin intake at T1 was associated with a lower subscore on two SAQ items: pleasure (1.8 ± 0.8 vs 2.2 ± 0.9, P = .02), and satisfaction with frequency of intercourse (1.2 ± 1.2 vs 1.8 ± 1.1, P = .02). In the overall population, dyspareunia VAS and quality of life assessed by EQ-5D improved between T0 and T1 (45 ± 29 at T0 vs 28 ± 29 at T1, P < .001; 0.78 ± 0.14 at T0 vs 0.86 ± 0.14 at T1, P < .001, respectively). At T1, the groups did not differ significantly for dyspareunia VAS (effect size 0.36 [95% CI -0.06 to 0.78], P = .10) and quality of life (EQ-5D, effect size 0.02 [95% CI -0.40 to 0.44], P = .91). CONCLUSION: In this observational study, high-dose progestins impair the sexual function of women treated for endometriosis even though they improved dyspareunia.

Positive and negative side effects of androgen abuse. The HAARLEM study: A one-year prospective cohort study in 100 men.

An estimated 4-6% of fitness center visitors uses anabolic-androgenic steroids (AAS). Reliable data about adverse reactions of AAS are scarce. The HAARLEM study aimed to provide insight into the positive and negative effects of AAS use. One hundred men (≥18 years) who intended to start an AAS cycle on short notice were included for follow-up. Clinic visits took place before (T0 ), at the end (T1 ), and three months after the end of the AAS cycle (T2 ), and one year after the start of the cycle (T3 ), and comprised a medical history, physical examination, laboratory analysis, and psychological questionnaires. During the follow-up period, four subjects reported a serious adverse event, that is, congestive heart failure, acute pancreatitis, suicidal ideation, and exacerbation of ulcerative colitis. All subjects reported positive side effects during AAS use, mainly increased strength (100%), and every subject reported at least one negative health effect. Most common were fluid retention (56%) and agitation (36%) during the cycle, and decreased libido (58%) after the cycle. Acne and gynecomastia were observed in 28% and 19%. Mean alanine transaminase (ALT) and creatinine increased 18.7 U/l and 4.7 µmol/L, respectively. AAS dose and cycle duration were not associated with the type and severity of side effects. After one-year follow-up (T3 ), the prevalence of observed effects had returned to baseline. There was no significant change in total scores of questionnaires investigating wellbeing, quality of life, and depression. In conclusion, all subjects experienced positive effects during AAS use. Four subjects experienced a serious adverse event. Other side effects were mostly anticipated, mild, and transient.

Lifestyle modifications alone or combined with hormonal contraceptives improve sexual dysfunction in women with polycystic ovary syndrome.

OBJECTIVE: To describe the prevalence of female sexual dysfunction in a well-defined polycystic ovary syndrome (PCOS) population, and to assess the impact of common PCOS treatments on sexual function. DESIGN: Secondary analysis of a randomized controlled trial, oral contraceptive pills and weight loss in PCOS. SETTING: Two academic medical centers. PATIENTS: Women with PCOS (N = 114) defined by the Rotterdam criteria. INTERVENTIONS: Continuous oral contraceptive pill (OCP) or intensive lifestyle modification (Lifestyle) or the combination (Combined) for 16 weeks. MAIN OUTCOME MEASURES: Change in Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised (FSDS-R) scores after 16 weeks. RESULTS: There was no change in total FSFI or FSDS-R score in any treatment group; however, an increase in the FSFI desire domain subscore was observed in the Lifestyle and Combined treatments, indicating improved sexual desire over the 16-week period. Overall, 33 participants (28.9%) met criteria for sexual dysfunction by FSFI criteria (baseline score ≤26.55). Among this group, FSFI score improved after 16 weeks of Lifestyle and Combined treatments. There was no change in prevalence of sexual dysfunction in treatment groups at 16 weeks. Use of OCPs did not alter FSFI scores. CONCLUSION(S): Female sexual dysfunction is highly prevalent among women with PCOS. Our findings suggest that common treatments for PCOS, including intensive lifestyle modification and the combination of intensive lifestyle modification and OCPs, have the potential to improve sexual function in these women; the mechanism for these improvements is likely multifactorial. CLINICAL TRIAL REGISTRATION NUMBER: NCT00704912.

Pharmacological treatment of lower urinary tract symptoms in benign prostatic hyperplasia: consequences on sexual function and possible endocrine effects.

INTRODUCTION: Benign prostate hyperplasia (BPH) is one of the most prevalent diseases in aging men. It may adversely affect quality-of-life due to the presence of low urinary tract symptoms (LUTS) and its effects on sexuality. AREAS COVERED: The impact of α1-blockers, 5α-reductase inhibitors (5-ARI), and phosphodiesterase 5 inhibitors (PDE-5i) on erectile and ejaculatory functions in men with BPH are covered. Endocrinological aspects have also been addressed, including the management of hypogonadism, which affects many patients with BPH, and the impact of the use of 5-ARI use on bone health. EXPERT OPINION: The adverse-event profile of α1-blockers depends on their affinity for the α1-adrenoceptors rather than selectivity. The probability of ejaculatory dysfunction is highest with silodosin than other nonselective drugs (tamsulosin, alfuzosin, doxazosin, and terazosin). Concerning the impact of finasteride and dutasteride on sexual desire, erectile function, and ejaculation, the vast majority of the studies have shown a low prevalence of treatment-related adverse events. Due to the benefits of erection, PDE5i represents the perfect class of drugs for the treatment of LUTS-BPH in patients with erectile dysfunction. Testosterone replacement therapy could be considered in some hypogonadal patients with BPH. Finally, current evidence support the safety of 5-ARI on bone tissue.

Acute caffeine reverses the disruptive effects of chronic fluoxetine on the sexual behavior of female and male rats.

RATIONALE: Sexual side effects of chronic treatment with selective serotonin reuptake inhibitors (SSRIs) in humans include anorgasmia and loss of sexual desire and/or arousal which interferes with treatment compliance. There are few options at present to reduce these effects. Because orgasm and desire are mediated in part by activation of sympathetic arousal, we asked whether the sympathomimetic effects of acute caffeine treatment could reverse these effects. OBJECTIVE: The present study examined whether acute treatment with caffeine (CAF; 10 or 20 mg/kg, ip) versus vehicle could ameliorate the disruption of appetitive and consummatory measures of copulatory behavior produced by chronic fluoxetine (10 mg/kg, sc) in adult, sexually active female or male rats. METHODS: Sexually experienced female or male rats received daily injections of FLU over a 24-day period and were tested for sexual behaviors five times at 4-day intervals during this period in bilevel pacing chambers. Females had been ovariectomized and given hormone replacement with estradiol benzoate and progesterone prior to each test. Males were left gonadally intact. Four days after the final FLU test, rats were randomly assigned to one of the three doses of CAF and received ip injections of CAF or the saline vehicle 60 min before testing. RESULTS: Chronic FLU reduced solicitations and lordosis over time in females and reduced the number of ejaculations in males. Both doses of CAF restored solicitations and lordosis in females and ejaculations in males. On their own, both doses of CAF increased females' pacing behavior and the number of mounts and intromissions in the males. CONCLUSIONS: Stimulation of sympathetic outflow by CAF may constitute a readily accessible on-demand treatment for the sexual side-effects of SSRIs.

Converting Men From Clomiphene Citrate to Natesto for Hypogonadism Improves Libido, Maintains Semen Parameters, and Reduces Estradiol.

OBJECTIVE: To evaluate outcomes including libido, semen parameters, testosterone, estradiol (E2), follicle stimulating hormone (FSH), and luteinizing hormone when converting men with low libido on Clomiphene Citrate (CC) to Natesto. METHODS: A retrospective chart review was performed. Baseline hormones prior to treatment, and again on CC and Natesto, as well as semen parameters on CC and on Natesto were assessed. RESULTS: In 41 men, there was no difference in serum testosterone levels on CC vs Natesto, however; there was a significantly higher E2 on CC than on Natesto. Although FSH levels were significantly lower on Natesto than at baseline, the mean FSH level on Natesto remained in the normal reference range. There was no difference in luteinizing hormone levels at baseline vs on Natesto. There was not a significant difference in semen parameter values when men were on CC vs when they were on Natesto for 3 months. At 3 months after changing to Natesto, 38 of 41 (92.7%) men reported significantly improved libido on Natesto when compared to CC. CONCLUSION: Men on CC and Natesto reach eugonadal testosterone levels, however; on CC the E2 level nearly doubled from baseline, and converting men from CC to Natesto returned E2 to nearly baseline levels. There was not a detrimental effect on semen parameters, and there was subjective reporting of improved libido after converting from CC to Natesto in this cohort, but further long-term studies are needed prior to Natesto being established as a definitive treatment for hypogonadism for men desiring to maintain fertility.