Long-term sexual functioning in germ-cell tumor survivors.

BACKGROUND: Survivors of germ-cell tumors (GCT) may suffer from long-term adverse consequences. Our study was conducted to assess a long-term sexual functioning in GCT survivors. METHODS: GCT survivors (N = 170) from the National Cancer Institute in Slovakia completed a Sexual Function Questionnaire that was modified from PROMIS Sexual Function and Satisfaction Questionnaire 9-year median follow up (range 5-32) as a primary exploratory aim. Study groups consisted of 17 survivors (10%) who had active surveillance (AS, controls), and 153 (90%) survivors who received treatment beyond orchiectomy (Tx), including cisplatin-based chemotherapy (CT, N = 132; 78%), radiotherapy to the retroperitoneal lymph nodes (RT, N = 12; 7%) or both (CTRT, N = 9; 5%). RESULTS: In univariate analysis, treatment of any type resulted in difficulty to maintain erection during sexual intercourse compared to patients treated with AS (P = 0.04). Survivors who received CTRT had lower ability to achieve orgasm during sexual activities (P = 0.04) and they reported disappointment with their overall quality of sex life (P = 0.002). The number of attempts to initiate sexual intercourse did not differ. Sexual relationships caused none or mild anxiety and the desire to be sexually active was higher after CTRT (P = 0.05). Multivariable analysis confirmed that orgasmic dysfunction after ≥400 mg/m2 of cisplatin and issues in maintaining erection after Tx were independent of retroperitoneal lymph-node dissection (P = 0.03 and P = 0.04, respectively). Survivors were disappointed with the quality of sex life and had stronger desire to be sexually active independent of age, (P = 0.01 and P = 0.05, respectively). CONCLUSIONS: This study identified an impairment in sexual function may represent an issue for long-term GCT survivors. Treatment with chemotherapy plus radiotherapy were associated with disappointment and stronger sexual desire, while a higher cumulative dose of cisplatin may be responsible for orgasmic dysfunction.

Topical Alpha-1 Adrenergic Receptor Agonist Applied to the Nipple/Areola Complex Improves Female Orgasmic Function.

Background: The impact of nipple sensation and its relationship to sexual function have often been neglected in medical literature. However, several recent studies report the importance of the nipple/areola complex (NAC) in sexual arousal and overall function. The nipple is composed of smooth muscle that can be erected via adrenergic nerves. In two complementary studies, we demonstrate that stimulation of the alpha-1 adrenergic receptor in the NAC with topical adrenergic agents can initiate erection of the nipple, increase NAC sensitivity, and improve sexual function. Materials and Methods: Thirteen breast surgery patients with nipple sensitivity loss were recruited to an unblinded study of topical phenylephrine hydrochloride. Sensitivity to pressure was measured before and after the application of the intervention to the NAC. In a second pilot study, 35 women completed a double-blinded placebo-controlled trial of a novel formulation, RJ101, containing a norepinephrine releasing agent. The intervention or placebo was applied to the NAC 30 minutes before sexual activity over the 4-week trial period. The arousal, lubrication, and orgasm domains of the female sexual function index (FSFI) were used to measure sexual function. Results: The application of phenylephrine hydrochloride was shown to increase nipple sensitivity to pressure by an average of 20% in our cohort of 13 breast augmentation patients. In addition, it was shown that intermittent application of the alpha-1 agonist for 8 weeks increased basal NAC sensitivity. In the follow-up pilot study, we demonstrate that stimulation of the NAC with RJ101 produced statistically significant increases versus placebo in the lubrication and orgasm domains of the FSFI, p = 0.0226 and p = 0.0269, respectively. Conclusion: For the first time, we demonstrate that the application of a topical alpha-1 adrenergic receptor agonist or a norepinephrine-releasing agent increases the sensitivity of the NAC and subsequently significantly improves sexual function.

Oestrogen versus androgen in hormone-replacement therapy for complete androgen insensitivity syndrome: a multicentre, randomised, double-dummy, double-blind crossover trial.

BACKGROUND: Women with complete androgen insensitivity syndrome (CAIS) after gonadectomy have complained about reduced psychological wellbeing and sexual satisfaction. The aim of this study was to compare the effectiveness of hormone-replacement therapy with either androgen or oestrogen in women with 46,XY karyotype and CAIS after gonadectomy. METHODS: This national, multicentre, double-blind, randomised crossover trial was performed at three university medical centres and three specialised treatment institutions in Germany. Eligible participants were women aged 18-54 years with 46,XY karyotype, genetically diagnosed CAIS, and removed gonads. Participants were randomly assigned (14:12) by a central computer-based minimisation method to either oestradiol 1·5 mg/day for 6 months followed by crossover to testosterone 50 mg/day for 6 months (sequence A) or to testosterone 50 mg/day for 6 months followed by crossover to oestradiol 1·5 mg/day for 6 months (sequence B). Participants also received oestradiol or testosterone dummy to avoid identification of the active substance. All participants received oestradiol 1·5 mg/day during a 2 months' run-in phase. The primary outcome was mental health-related quality of life, as measured with the standardised German version of the SF-36 questionnaire. Secondary outcomes were psychological wellbeing, as measured with the Brief Symptom Inventory (BSI), sexual function, as measured with the Female Sexual Function Index (FSFI), and somatic effects, such as signs of virilisation and effects on metabolic blood values. The primary analysis included all patients who were available at least until visit 5, even if protocol violations occurred. The safety analysis included all patients who received at least oestradiol during the run-in phase. This trial is registered with the German Clinical Trials Register, number DRKS00003136, and with the European Clinical Trials Database, number 2010-021790-37. FINDINGS: We enrolled 26 patients into the study, with the first patient enrolled on Nov 7, 2011, and the last patient leaving the study on Jan 23, 2016. 14 patients were assigned to sequence A and 12 were assigned to sequence B. Ten participants were withdrawn from the study, two of whom attended at least five visits and so could be included in the primary analysis. Mental health-related quality of life did not differ between treatment groups (linear mixed model, p=0·794), nor did BSI scores for psychological wellbeing (global severity index, p=0·638; positive symptom distress index, p=0·378; positive symptom total, p=0·570). For the FSFI, testosterone was superior to oestradiol only in improving sexual desire (linear mixed model, p=0·018). No virilisation was observed, and gonadotrophin concentrations remained stable in both treatment groups. Oestradiol and testosterone concentrations changed substantially during the study in both treatment groups. 28 adverse events were reported for patients receiving oestradiol (23 grade 1 and five grade 2), and 38 adverse events were reported for patients receiving testosterone (34 grade 1, three grade 2, and one grade 3). One serious adverse event (fibrous mastopathy) and 20 adverse events (16 grade 1 and four grade 2) were reported during the run-in phase, and 12 adverse events during follow-up (nine grade 1 and three grade 2). INTERPRETATION: Testosterone was well tolerated and as safe as oestrogen for hormone-replacement therapy. Testosterone can be an alternative hormone substitution in CAIS, especially for woment with reduced sexual functioning. FUNDING: German Federal Ministry of Education and Research.

Testosterone therapy for sexual dysfunction in men with Type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials.

AIM: To evaluate the effectiveness of testosterone therapy on a range of sexual function domains in men with Type 2 diabetes. METHOD: Electronic databases were searched for studies investigating the effect of testosterone therapy on sexual function in men with Type 2 diabetes. All randomized controlled trials were considered for inclusion if they compared the efficacy of testosterone therapy with that of placebo and reported sexual function outcomes. Statistical analysis was performed using a random-effects model, and heterogeneity was expressed using the I2 statistic. RESULTS: A total of 611 articles were screened. Six randomized control trials, in a total of 587 men with Type 2 diabetes, were eligible for inclusion. The pooled data suggested that testosterone therapy improves sexual desire (random-effects pooled effect size 0.314; 95% CI 0.082-0.546) and erectile function (random-effects pooled effect size 0.203; 95% CI 0.007-0.399) when compared with control groups. Testosterone therapy had no significant effect on constitutional symptoms or other sexual domains compared with control groups. No studies have investigated the incidence of prostate cancer, fertility and cardiovascular disease after testosterone therapy in men with Type 2 diabetes. CONCLUSION: Testosterone therapy may moderately improve sexual desire and erectile function in men with Type 2 diabetes; however, available data are limited, and the long-term risks of testosterone therapy are not known in this specific patient group. We conclude that testosterone therapy is a potential treatment for men with Type 2 diabetes non-responsive to phosphodiesterase-5 inhibitors. Testosterone therapy could be considered for men with Type 2 diabetes when potential risks and benefits of therapy are carefully considered and other therapeutic options are unsuitable.

External Beam Radiation Therapy or Brachytherapy With or Without Short-course Neoadjuvant Androgen Deprivation Therapy: Results of a Multicenter, Prospective Study of Quality of Life.

PURPOSE: The long-term effects of neoadjuvant androgen deprivation therapy (NADT) with radiation therapy on participant-reported health-related quality of life (HRQOL) have not been characterized in prospective multicenter studies. We evaluated HRQOL for 2 years among participants undergoing radiation therapy (RT) with or without NADT for newly diagnosed, early-stage prostate cancer. METHODS AND MATERIALS: We analyzed longitudinal cohort data from the Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment Consortium to ascertain the HRQOL trajectory of men receiving NADT with external beam RT (EBRT) or brachytherapy. HRQOL was measured using the expanded prostate cancer index composite 26-item questionnaire at 2, 6, 12, and 24 months after the initiation of NADT. We used the χ2 or Fisher exact test to compare the shift in percentages between groups that did or did not receive NADT. Analyses were conducted at the 2-sided 5% significance level. RESULTS: For subjects receiving EBRT, questions regarding the ability to have an erection, ability to reach an orgasm, quality of erections, frequency of erections, ability to function sexually, and lack of energy were in a significantly worse dichotomized category for the patients receiving NADT. Comparing the baseline versus 24-month outcomes, 24%, 23%, and 30% of participants receiving EBRT plus NADT shifted to the worse dichotomized category for the ability to reach an orgasm, quality of erections, and ability to function sexually compared with 14%, 13%, and 16% in the EBRT group, respectively. CONCLUSIONS: Compared with baseline, at 2 years, participants receiving NADT plus EBRT compared with EBRT alone had worse HRQOL, as measured by the ability to reach orgasm, quality of erections, and ability to function sexually. However, no difference was found in the ability to have an erection, frequency of erections, overall sexual function, hot flashes, breast tenderness/enlargement, depression, lack of energy, or change in body weight. The improved survival in intermediate- and high-risk patients receiving NADT and EBRT necessitates pretreatment counseling of the HRQOL effect of NADT and EBRT.

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.

Efficacy and safety of transdermal testosterone in postmenopausal women with hypoactive sexual desire disorder: a systematic review and meta-analysis.

OBJECTIVE: To systematically review and summarize the existing evidence related to the efficacy and safety of transdermal T in postmenopausal women for the treatment of hypoactive sexual desire disorder (HSDD). DESIGN: Systematic reviews and meta-analysis. SETTING: Not applicable. PATIENT(S): Seven randomized controlled trials enrolled 3,035 participants; 1,350 women were randomized to treatment with T patch, and 1,379 women were randomized to placebo. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Primary outcome: satisfying sexual episodes. SECONDARY OUTCOMES: sexual activity, orgasm, Profile of Female Sexual Function domains (desire), personal distress score, adverse events, acne, increased hair growth, facial hair, alopecia, voice deepening, urinary symptoms, breast pain, headache, site reaction, total adverse events, serious adverse events, withdrawal from study, and follow-up rate. RESULT(S): The T group had significantly more satisfying sexual episodes, sexual activity, orgasms, desire, significant change in Personal Distress Scale score, androgenic adverse events, acne, and hair growth compared with the placebo group. There was no significant difference between the two groups in increase in facial hair, alopecia, voice deepening, urinary symptoms, breast pain, headache, site reaction to the patch, total adverse events, serious adverse events, reasons for withdrawal from the study, and the number of women who completed the study. CONCLUSION(S): The short-term efficacy in terms of improvement of sexual function and safety of transdermal T in naturally and surgically menopausal women affected by HSDD either on or not on estrogen progestin hormone therapy is evident from this systematic review. The use of transdermal T is associated with increase in androgenic adverse events such as acne but is not associated with any serious adverse events.

Influence of Dyslipidemia on the Quality of Sexual Life in Women in the Menacme using a Combined Oral Contraceptive / Influência da dislipidemia na qualidade de vida sexual de mulheres na menacme usando contraceptivos orais combinados

ABSTRACT Purpose: Female sexual dysfunction is a complex and common condition that affects women, and the relationship between sexual function and dyslipidemia is poorly studied. This study aims to assess this relationship in the reproductive life women in the menacme who use combined oral contraceptives (COCs) . Methods: A total of 49 healthy women who were sexually active received COC pills that contained ethinylestradiol 30 mcg (EE30) plus levonorgestrel 150 mcg (LNG150). The women were divided into two groups according to their lipid profiles. Dyslipidemia was defined as a high-density lipoprotein (HDL) level < 50 mg/dL or a low-density lipoprotein (LDL) level > 130 mg/dL. Sexual function was assessed using the Female Sexual Function Index (FSFI) Questionnaire. Lipid and lipoprotein parameters were obtained at baseline and after the sixth cycle. Results: After six cycles of the COCs, the total cholesterol and LDL cholesterol levels in the women with a LDL level > 130 mg/dL decreased by 14.7% and 22.1% respectively. In the women with a HDL level < 50 mg/dL at baseline, the HDL level increased by 15.5% at the end of the study. The arousal and orgasm domains and the FSFI total scores significantly increased in women with and without dyslipidemia. The desire and satisfaction domains increased only in the group without dyslipidemia at the end of the treatment period. Conclusions: The EE30/LNG150 formulation increased the sexual function and it was only positively correlated with the HDL cholesterol level. These data indicated a low correlation between sexual function and the changes in the lipid and lipoprotein metabolism.

RESUMO Objetivo: Disfunção sexual feminina é uma condição complexa acomete as mulheres, e a relação entre a função sexual e a dislipidemia é muito pouco estudada. Este estudo objetivou avaliar esta relação em mulheres na menacme que fazem uso de contraceptivos orais combinados (COCs). Métodos: Um total de 49 mulheres saudáveis com vida sexual ativa receberam pílulas anticoncepcionais contendo etinilestradiol 30 mcg (EE30) associado a levonorgestrel 150 mcg (LNG150). As mulheres foram divididas em dois grupos, de acordo com o perfil lipídico. Dislipidemia foi definida como nível de lipoproteína de alta densidade (HDL) < 50 mg/dL, ou nível de lipoproteína de baixa densidade (LDL) > 130 mg/dL. A função sexual feminina foi avaliada utilizando o questionário de Índice de Função Sexual Feminina (IFSF). O IFSF e os parâmetros lipídicos e lipoproteicos foram obtidos no início e após o sexto ciclo do estudo. Resultados: Após seis ciclos de uso dos COCs, as mulheres com LDL > 130 mg/dL, tiveram redução dos níveis de colesterol total e colesterol LDL de 14,7% e 22,1% respectivamente. Nas mulheres com níveis HDL < 50 mg/dL no momento basal, o nível de HDL aumentou 15,5% ao final do estudo. Os domínios de excitação, orgasmo e os escores totais do IFSF aumentaram significativamente nas mulheres com e sem dislipidemia. Os domínios de desejo e satisfação aumentaram no final do período de tratamento exclusivamente no grupo sem dislipidemia. Conclusões: A formulação EE30/LNG150 aumentou a função sexual das mulheres, sendo positivamente correlata somente com os níveis de colesterol HDL. Estes achados demonstram baixa correlação entre a função sexual e as alterações no metabolismo lipídico e lipoproteico.

TX-004HR Improves Sexual Function as Measured by the Female Sexual Function Index in Postmenopausal Women With Vulvar and Vaginal Atrophy: The REJOICE Trial.

INTRODUCTION: TX-004HR is an investigational, applicator-free, vaginal soft gel capsule containing low-dose solubilized 17ß-estradiol. The phase 3, randomized, double-blinded, placebo-controlled, multicenter REJOICE trial has shown TX-004HR to be safe and effective for the treatment of moderate to severe dyspareunia in postmenopausal women with vulvar and vaginal atrophy (VVA). AIM: To evaluate the effect of TX-004HR on female sexual dysfunction in postmenopausal women with VVA. METHODS: The REJOICE study compared the effects of 12-week treatment with TX-004HR (4, 10, or 25 µg) with placebo in postmenopausal women (40-75 years old) with VVA and a most bothersome symptom of moderate to severe dyspareunia. Changes in the percentage of superficial and parabasal cells, vaginal pH, and dyspareunia were measured as co-primary end points. Female sexual dysfunction was evaluated as a secondary end point using the Female Sexual Function Index (FSFI) patient self-report inventory. MAIN OUTCOME MEASURES: Changes from baseline to week 12 in total and individual domain FSFI scores for each TX-004HR dose were compared with those for placebo. RESULTS: All three TX-004HR doses increased the baseline total FSFI score after 12 weeks, with 10 µg (P < .05) and 25 µg (P = .0019) having a significantly greater effect than placebo. A similar trend was observed for the individual FSFI domains, with 10 and 25 µg significantly improving baselines scores for pain and lubrication at 12 weeks (P ≤ .015 for all vs placebo). Changes from baseline to week 12 in arousal (P = .0085) and satisfaction (P = .0073) were significantly greater for TX-004HR 25 µg vs placebo. All three TX-004HR doses were comparable to placebo in their effect on desire and orgasm. CONCLUSION: TX-004HR improved FSFI scores in a dose-dependent manner. The observed improvements in sexual function suggest that TX-004HR is a promising treatment option for postmenopausal VVA with a potential added beneficial effect on female sexual dysfunction.

Effects of 8-Year Treatment of Long-Acting Testosterone Undecanoate on Metabolic Parameters, Urinary Symptoms, Bone Mineral Density, and Sexual Function in Men With Late-Onset Hypogonadism.

INTRODUCTION: The long-term effects of long-acting testosterone undecanoate (TU) and androgen receptor CAG repeat lengths in Thai men with late-onset hypogonadism (LOH) have not been reported. AIM: To analyze the 8-year follow-up effects of intramuscular TU therapy on metabolic parameters, urinary symptoms, bone mineral density, and sexual function and investigate CAG repeat lengths in men with LOH. METHODS: We reviewed the medical records of 428 men with LOH who had been treated with TU and 5 patients were diagnosed with prostate cancer during TU therapy. There were 120 patients (mean age = 65.6 ± 8.9 years) who had 5 to 8 years of continuous TU supplementation and sufficiently completed records for analysis. Genomic DNA was extracted from peripheral blood and the CAG repeat region was amplified by polymerase chain reaction. Fragment analysis, sequencing, electropherography, and chromatography were performed. MAIN OUTCOME MEASURES: The main outcome measure was dynamic parameter changes during testosterone supplementation. RESULTS: TU did not improve all obesity parameters. A statistically significant decrease was found in waist circumference, percentage of body fat, glycated hemoglobin, cholesterol, low-density lipoprotein, and International Prostate Symptom Score (P < .05). TU did not produce differences in body mass index, high-density lipoprotein, triglyceride, or the Aging Male Symptoms score from baseline. However, a statistically significant increase was found in the level of testosterone, prostate-specific antigen, hematocrit, International Index of Erectile Function score, and vertebral and femoral bone mineral density (P < .05). No major adverse cardiovascular events or prostate cancer occurred during this study. The CAG repeat length was 14 to 28 and the median CAG length was 22. There was no association between CAG repeat length and any of the anthropometric measurements. CONCLUSION: Long-term TU treatment in men with LOH for up to 8 years appears to be safe, tolerable, and effective in correcting obesity parameters.

Impact of Testosterone Solution 2% on Ejaculatory Dysfunction in Hypogonadal Men.

INTRODUCTION: Hypogonadism is defined as decreased testosterone levels in men. Hypogonadism can be accompanied by erectile, orgasmic, and ejaculatory dysfunction. AIMS: To evaluate whether treatment with testosterone solution 2% (testosterone) could improve ejaculatory function in a cohort of hypogonadal men. METHODS: Sexually active, hypogonadal men at least 18 years old (total testosterone < 300 ng/dL) were randomized to receive testosterone or placebo for 12 weeks. MAIN OUTCOME MEASURES: Effects of testosterone on primary outcomes were evaluated using the International Index of Erectile Function (IIEF) and the Men's Sexual Health Questionnaire, Ejaculatory Dysfunction, Short Form (MSHQ-EjD-SF) questionnaires. Treatment differences were calculated using analysis of covariance. RESULTS: In total, 715 men (mean age = 55 years) were randomized to placebo (n = 357) or testosterone (n = 358). Most sexually active men who reported IIEF scores had some degree of erectile dysfunction (IIEF erectile function score < 26). Although ejaculatory function score (MSHQ-EjD-SF) improved in the testosterone group compared with placebo (P < .001), improvement on the "bother" item did not reach statistical significance. Treatment-related adverse events in the testosterone group affecting at least 1% of patients were increased hematocrit, upper respiratory tract infection, arthralgia, burning sensation, fatigue, increased prostate-specific antigen, erythema, and cough. Few patients in either treatment group developed at least one adverse event leading to discontinuation (testosterone = 1.98% vs placebo = 3.09%; P = .475). CONCLUSION: Hypogonadal men receiving testosterone solution 2% therapy experience significantly greater improvement in ejaculatory function, compared with placebo, as assessed by the MSHQ-EjD-SF. However, improvement in "bother" was not statistically different between the two groups. Testosterone therapy was generally well tolerated.

Sexual healing in patients with prostate cancer on hormone therapy.

Since prostate cancer becomes more common with age, at least one-third of men have sexual problems at diagnosis. All localized treatments for prostate cancer greatly increase the prevalence of sexual dysfunction, which include loss of desire, erectile dysfunction, and changes in orgasm. Even men on active surveillance have a higher rate of problems than matched peers without prostate cancer. However, men given androgen deprivation therapy (ADT) have the worst rates of sexual dysfunction. Even after 3 to 4 months of ADT, men's desire for sex is decreased and irreversible damage may occur to the erectile tissue in the penis. Erections do not recover in about one-half of men, even if ADT is discontinued. Although intermittent ADT allows some recovery of sexual function, serum testosterone requires 9 to 12 months off ADT to recover. Again, one-half of men have permanent erectile dysfunction. If ADT causes atrophy of the erectile tissue, blood leaks out of the venous system during erection. This syndrome is difficult to treat except with surgery to implant a penile prosthesis. Despite the high rate of sexual problems in men on ADT, a small group stays sexually active and is able to have reliable erections. To improve men's sexual satisfaction on ADT, it may be important to educate them about getting extra mental and physical sexual stimulation, as well as using penile rehabilitation during hormone therapy. Information on reaching orgasm and coping with problems such as dry orgasm, pain with orgasm, and urinary incontinence during sex also should be provided.

Sexual function in women on estradiol or venlafaxine for hot flushes: a randomized controlled trial.

OBJECTIVE: To evaluate sexual function in midlife women taking low-dose oral estradiol or venlafaxine for hot flushes. METHODS: In an 8-week randomized controlled trial among women aged 40-62 years, sexual function was compared between 0.5 mg oral estradiol per day or 75 mg venlafaxine per day (both compared with a placebo). Measures included composite and six domain scores from the Female Sexual Function Index and sexually related personal distress. RESULTS: Participants were aged 54.6 years (standard deviation [SD] 3.8) years, 59% white, with 8.1 (SD 5.3) daily hot flushes. Median composite baseline Female Sexual Function Index score was 16.3 (SD 11.9, n=256) for all women and 21.7 (SD 9.3, n=198) among sexually active women. Composite mean Female Sexual Function Index change from baseline to week 8 was 1.4 (95% confidence interval [CI] -0.4 to 3.2) for estradiol, 1.1 (95% CI -0.5 to 2.7) for venlafaxine, and -0.3 (95% CI -1.6 to 1.0) for placebo. Composite Female Sexual Function Index and sexually related distress change from baseline did not differ between estradiol and placebo (P=.38, P=.30) or venlafaxine and placebo (P=.79, P=.48). Among sexually active women, Female Sexual Function Index domain score change from baseline differences (active compared with placebo) in desire was 0.3 (95% CI 0.0-0.6) for estradiol, -0.6 (95% CI -1.2 to 0.0) in orgasm for venlafaxine, and 0.9 (95% CI 0.2-1.6) in penetration pain for venlafaxine. No women reported adverse events related to sexual dysfunction. CONCLUSION: Overall sexual function among nondepressed midlife women experiencing hot flushes did not change over 8 weeks with low-dose oral estradiol or venlafaxine (compared with placebo), although a subtle increase in desire (estradiol) and decreases in orgasm and pain (venlafaxine) may exist. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01418209. LEVEL OF EVIDENCE: I.

Lack of influence of dyspareunia on the beneficial effect of intravaginal prasterone (dehydroepiandrosterone, DHEA) on sexual dysfunction in postmenopausal women.

INTRODUCTION: We have previously observed that intravaginal prasterone (dehydroepiandrosterone, DHEA) improved all domains of female sexual dysfunction (FSD). AIM: Investigate the influence of moderate/severe pain at sexual activity (dyspareunia) (MSD) at baseline on FSD following prasterone administration. METHODS: The effect of daily administration of prasterone (0, 3.25 mg, 6.5 mg or 13 mg) for 12 weeks on FSD in 215 postmenopausal women with or without MSD at baseline was evaluated in a prospective, randomized, double-blind, and placebo-controlled phase III clinical trial. MAIN OUTCOME MEASURES: Differences were examined on desire, arousal and orgasm. RESULTS: Comparable benefits were observed in women not having MSD (n = 56) vs. those having MSD (n = 159). The benefits over placebo in prasterone-treated women for desire, avoiding intimacy and vaginal dryness as well as for the total sexual domain of the MENQOL (Menopause Specific Quality of Life) questionnaire, ranged between 18.0% and 38.2% with P values of <0.05 or <0.01 except in one out of 12 subgroups. For the arousal/sensation, arousal/lubrication and summary score of the ASF (Abbreviated Sexual Function) questionnaire, in the MSD+ group, improvements of 64.2% (P = 0.01), 118% (P = 0.001) and 31.1% (P = 0.03) were observed over placebo, respectively, while similar differences (58.0%, 67.6% and 32.1%) did not reach statistical significance in the MSD- group having up to only 44 prasterone-treated women compared with 119 in the MSD+ group. CONCLUSIONS: No MSD at baseline does not apparently affect the effects of intravaginal prasterone on sexual dysfunction. Knowing the absence of significant effects of estrogens on FSD, the present data suggest that vulvovaginal atrophy (VVA) and vulvovaginal sexual dysfunction (VVSD) are two different consequences of sex steroid deficiency at menopause which can respond independently. In addition, the present data seriously question the justification of pain being part of FSD as well as the separation of FSD into separate domains.

Efficacy of vaginally applied estrogen, testosterone, or polyacrylic acid on sexual function in postmenopausal women: a randomized controlled trial.

INTRODUCTION: Female libido is multifactorial and complex. Declining estrogen levels in postmenopausal women affects vaginal function. AIM: The aim of this study was to evaluate female sexual function after using topical estrogen, testosterone, or polyacrylic acid as vaginal lubricants with K-Y jelly as a placebo lubricant. METHODS: This was a randomized controlled clinical trial on 80 postmenopausal women between 40 and 70 years of age with follow-up at the Menopause Clinic of the CAISM Unicamp. The women were randomized to treatment with topical vaginal estrogen, testosterone, polyacrylic acid, or oil lubricant alone, three times a week for a period of 12 weeks from November 2011 to January 2013. MAIN OUTCOME MEASURE: We used the Female Sexual Function Index (FSFI) to assess changes in sexual response at baseline, and after 6 and 12 weeks. RESULTS: After 12 weeks of treatment, polyacrylic acid and topical testosterone produced improvements in the FSFI domains of sexual desire, lubrication, satisfaction, reduced pain during intercourse, and total score compared with lubricant alone. Treatment with topical estrogen in comparison with lubricant alone showed an improvement in the FSFI field of desire. The intragroup analysis over the time of the treatment showed improvements in the fields of desire, lubrication, and reduced pain for polyacrylic acid, testosterone, and estrogen. Furthermore, women who used testosterone showed improvements over time in the fields of arousal, orgasm, and satisfaction. CONCLUSIONS: Treatment of postmenopausal women with symptoms of vaginal atrophy with polyacrylic acid, testosterone, and estrogen for 12 weeks produced improvements in self-reported female sexual function when compared with a placebo lubricant.

Effect of selective alpha-blocker tamsulosin on erectile function in patients with lower urinary tract symptoms due to benign prostatic hyperplasia.

OBJECTIVE: To study the effect selective of α-blocker (tamsulosin HCl) on erectile function in married male patients who are suspected to have benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Our study was a prospective randomized single blinded study in one-to-one fashion conducted upon 60 patients, all of them married, between May 2010 and May 2011, the patients under the study were attending the outpatient clinic of the New Kasr Al-Aini Teaching Hospital and Students Hospital, Cairo University, complaining of lower urinary tract symptoms (LUTS) either obstructive, irritative, or both and erectile dysfunction (ED). History was taken from all patients; all patients were examined by digital rectal examination and abdominal examination. We performed pelvic ultrasound, serum prostatic-specific antigen (PSA) measurements, other routine investigations, and uroflowmetry. Assessment of sexual function changes was by the International Index of Erectile Function (IIEF) and penile Doppler ultrasound. RESULTS: In the tamsulosin group, a significant statistical improvement was detected in the erectile function score and intercourse satisfaction score with significant improvement in total IIEF beside the improvement in the International Prostatic Symptom Score (IPSS). Although orgasmic function score showed significant worsening. CONCLUSION: Tamsulosin HCl capsules showed a significant statistical improvement in the erectile function, sexual desire, and intercourse satisfaction score with significant improvement in total IIEF in patients with lower urinary tract symptoms because of benign prostatic hyperplasia.

The effect of estrogen on the sexual interest of castrated males: Implications to prostate cancer patients on androgen-deprivation therapy.

Androgen deprivation therapy (ADT) for prostate cancer (PCa) treatment causes sexual dysfunction. We review here the effects of estrogen on the sexual performance of androgen-deprived males. The major findings are: 1. Estrogen receptors are present in brain centers that are important for sexual behavior; as well as in male reproductive organs, in a pattern suggesting that estrogen may have some role in orgasmic function and genital skin sensitivity. 2. Estrogen restores sexual interest above castrate levels in many vertebrates including reptiles, birds and mammals; but multiple factors contribute to the magnitude of this effect. 3. Data from castrated men, aromatase-deficient men, male-to-female transsexuals, and men on antiandrogens all suggest that estrogen can maintain some libido in androgen-deprived men. We discuss the general benefits of estrogen therapy to quality of life of men on ADT, the potential risks of this treatment, and possible treatment regimes for estrogen therapy in males. Unless contraindicated, we propose that PCa patients on ADT would benefit from supplemental parenteral estrogen.

Tadalafil once daily improves ejaculatory function, erectile function, and sexual satisfaction in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia and erectile dysfunction: results from a randomized, placebo- and tamsulosin-controlled, 12-week double-blind study.

INTRODUCTION: Tadalafil, a long-acting phosphodiesterase type 5 inhibitor, is approved for treating signs and symptoms of benign prostatic hyperplasia (BPH) and erectile dysfunction (ED); tamsulosin, an alpha-blocker, is approved for treating signs and symptoms of BPH. AIM: To determine the effects of tadalafil or tamsulosin on sexual function, including ejaculation and orgasm, satisfaction, and erectile function, in sexually active men with ED and lower urinary tract symptoms suggestive of BPH (LUTS/BPH). METHODS: A randomized, double-blind, placebo-controlled study of tadalafil 5 mg once daily for 12 weeks in men with LUTS/BPH; tamsulosin 0.4 mg once daily was an active control. MAIN OUTCOME MEASURES: The International Index of Erectile Function (IIEF) questionnaire was administered at baseline and 4, 8, and 12 weeks. Analysis of orgasm and ejaculation was post hoc based on the IIEF-Orgasmic Function (OF) domain (IIEF-Q9 [ejaculatory frequency] and Q10 [orgasmic frequency]). Other measures included IIEF-Intercourse Satisfaction (IS), Overall Satisfaction (OS), and Erectile Function (EF) domains. Changes from baseline to 12 weeks (or last observation) vs. placebo were analyzed using analysis of covariance. Higher IIEF scores indicate better functioning. RESULTS: Of 511 study participants, 310 (60.7%) had ED and were sexually active. The IIEF-OF increased significantly through 12 weeks with tadalafil vs. placebo (P = 0.048), as did IIEF-Q9 (P = 0.045) but not IIEF-Q10 (P = 0.100). Compared with placebo, IIEF-OF, Q9, and Q10 decreased significantly with tamsulosin (all P < 0.05). The IIEF-IS and OS increased significantly at end point with tadalafil (both P < 0.001); for tamsulosin, change was not significant for IS, while OS decreased significantly (P = 0.009). The IIEF-EF domain increased significantly vs. placebo with tadalafil (P < 0.001) but not tamsulosin (P = 0.699). CONCLUSIONS: Tadalafil 5 mg once daily significantly improved ejaculation and orgasm, intercourse and overall satisfaction, and erectile function. Men receiving tamsulosin 0.4 mg once daily experienced a decrease in both ejaculatory/orgasmic frequency and overall satisfaction vs. placebo, with no significant effect on erectile function.

Individual and dyadic barriers to a pharmacotherapeutic treatment of hypoactive sexual desire disorders: results and implications from a small-scale study with bupropion.

This article describes the results of an independent small-scale trial with the centrally acting agent bupropion for female hypoactive sexual desire disorder. The main goals were to gain insight into the intrapsychic and interpersonal barriers to improvement associated with the pharmacological treatment of this common disorder. Eligible subjects entered a 2-week run-in period and a 4-week placebo phase, followed by a 20-week treatment phase. In addition to semi-structured clinical interviews and a set of standardized questionnaires, we used 2 self-developed questionnaires, addressing the period between visits and the week preceding each visit. Participants were 16 women who entered the placebo phase and 10 who completed the medication period. Analyses of pre-post scores and of the questionnaire addressing the time between visits yielded no significant changes. The questionnaire focusing on the week preceding each visit indicated improvements in sexual desire, arousability, and orgasmic ease after Week 8. In the clinical interviews, half of the women reported subjective improvements of sexual desire and arousability that could not be transferred to the sexual relationship as a result of individual and dyadic barriers. Overall, a centrally acting agent such as bupropion may be a viable option for female sexual dysfunction, but it seems mandatory to embed it in a psychotherapeutic approach.