Sexual Motivators and Endorsement of Models Describing Sexual Response of Men Undergoing Androgen Deprivation Therapy for Advanced Prostate Cancer.

BACKGROUND: Androgen deprivation therapy (ADT) administered against metastatic prostate cancer has significant side effects including sexual dysfunction. AIM: To assess sexual interest and motivators for sex during ADT and to find out what model of sexuality best describes the sexual experience for men during this treatment. METHODS: A questionnaire was mailed to patients who had received ADT for ≥6 months. Patients were asked to choose all relevant entities from a list of sexual motivators and between models of sexuality described by Masters and Johnson (excitement and physical experiences), Kaplan (sexual desire), and Basson (intimacy and closeness to partner). Erectile function was assessed by the Erection Hardness Scale, and sexual satisfaction was measured on a scale from 0 to 10. OUTCOMES: Sexual activity, erectile function, sexual satisfaction, and motivators for sexual interest in the study subjects as well as the proportion of participants who endorsed either of the 3 models of sexuality. RESULTS: A total of 173 men were invited, and 76 returned the questionnaires (44%). The median age was 76 (range 69-80) years, and the median duration of ADT was 30 months. A total of 62 men had been sexually active before ADT, and of these, 2 were still active. Another 29 were interested in sexual activity. 3 men endorsed the Masters and Johnson model, whereas the remaining participants did not endorse any of the models. The motivators for sexual interest were feeling an emotional connection to the partner (n = 16), sexual desire (n = 10), satisfaction of the partner (n = 8), fear that the partner would leave (n = 4), achieving orgasm (n = 3), and a desire to feel masculine (n = 1). No one was interested in sexual activity to reduce stress or to maintain confidence. Only 1 patient had erections sufficient for penetrative intercourse, and the median sexual satisfaction for the entire group was 0 (interquartile range: 0-5). CLINICAL IMPLICATIONS: Sexuality and sexual function should be addressed in men undergoing ADT. STRENGTHS & LIMITATIONS: The main strength of our study is that we are the first to explore both motivators for sexual activity and endorsement of sexual models in men undergoing ADT. The study is limited by the relatively low number of participants and the response rate of 44%. CONCLUSION: ADT is detrimental to sexual function. However, many patients maintain an interest in sexual activity, which does not fit our established models. Rather, factors such as keeping an emotional connection with a partner play a role. Fode M, Mosholt KS, Nielsen TK, et al. Sexual Motivators and Endorsement of Models Describing Sexual Response of Men Undergoing Androgen Deprivation Therapy for Advanced Prostate Cancer. J Sex Med 2020;17:1538-1543.

Risk of Adverse Pregnancy Outcome After Paternal Exposure to Methotrexate Within 90 Days Before Pregnancy.

OBJECTIVE: To study the association between paternal exposure to methotrexate within the 90-day period before pregnancy and congenital malformations and stillbirth in the offspring. METHODS: We conducted a nationwide register study. Our cohort consisted of all live births in Denmark between 1997 and 2011 identified from the Medical Birth Registry. Methotrexate-exposed fathers were identified from the National Prescription Registry. From the national Hospital Registry we identified paternity, live births, and stillbirths as well as discharge diagnoses on congenital malformations. RESULTS: We identified 849,676 live births with known paternity. There were 127 live births of methotrexate-exposed fathers. Of these, four (3.2%) had major malformations compared with 28,814 (3.4%) of the unexposed. The odds ratio (OR) for major congenital malformation among exposed fathers compared with unexposed was 0.93 (95% confidence interval [CI] 0.34-2.51) and when adjusted for year of birth, maternal age, educational length, household income, and parity, the adjusted OR was 1.01 (95% CI 0.37-2.74). There were no stillbirths in the methotrexate-exposed group compared with 2,541 (0.3%) in the unexposed group and no increased risk of preterm birth (adjusted OR 1.31, 95% CI 0.66-2.59) among the children from exposed fathers. CONCLUSION: We found no association between paternal exposure to methotrexate within 90 days before pregnancy and congenital malformations, stillbirths, or preterm birth. Available data suggest that prepregnancy paternal methotrexate exposure should not be of major concern. Multinational recommendations should be changed accordingly.

Elevated prostate specific antigen and reduced 10-year survival among a cohort of Danish men consecutively referred from primary care to an urological department during 2005-2006.

It remains unclear whether total prostate specific antigen (tPSA) or complex PSA (cPSA) has the best diagnostic performance. Additionally, the utility of percentage free PSA (%fPSA) is still debated. Our objectives were to compare the diagnostic performances of tPSA, cPSA, and %fPSA among patients referred from GP to an Urological Specialist and to investigate prognostic factors and survival in the cohort. A total of 1261 consecutive male patients without previously known prostate cancer (PCa) were referred to the same Department of Urology during June 2005 to August 2006. Some 299 patients were diagnosed with PCa and 962 patients were found without PCa. Among the PCa patients, the median age, tPSA, cPSA, and %fPSA levels were 70.8 years, 13.4 µg/L, 10.8 µg/L, and 12.6%. For patients without PCa the results were 67.5 years, 2.5 µg/L, 1.9 µg/L, and 24.9%. The sensitivity, specificity, PVpos, PVneg, and efficiency of tPSA and cPSA were overlapping (p > .05). In the tPSA interval >4 µg/L - ≤20 µg/L, %fPSA excluded PCa with a PVneg of 72.4%; 38.5% of PCa patients had a tPSA concentration >20 µg/L at the time of referral and these patients had a reduced 10-year survival as compared to patients with tPSA concentrations ≤20 µg/L. In conclusion, tPSA and cPSA showed similar diagnostic performances. %fPSA provided additional diagnostic information at tPSA concentrations >4 µg - ≤20 µg/L. The high percentage of patients with tPSA concentrations >20 µg/L indicate delayed use of tPSA resulting in advanced disease at presentation and reduced patient survival.

Simvastatin and oxidative stress in humans: A randomized, double-blinded, placebo-controlled clinical trial.

Simvastatin reduces the blood concentration of cholesterol by inhibiting hydroxymethylglutaryl-coenzyme A reductase, the rate-limiting enzyme in cholesterol synthesis, and thereby reduces the risk of cardiovascular disease. In addition, simvastatin treatment leads to a reduction in fluxes in mitochondrial respiratory complexes I and II and might thereby reduce the formation of reactive oxygen species, which have been implicated in the pathogenesis of arteriosclerosis. Therefore, we hypothesized that simvastatin may reduce oxidative stress in humans in vivo. We conducted a randomized, double-blinded, placebo-controlled study in which subjects were treated with either 40mg of simvastatin or placebo for 14 days. The endpoints were six biomarkers for oxidative stress, which represent intracellular oxidative stress to nucleic acids, lipid peroxidation and plasma antioxidants, that were measured in urine and plasma samples. A total of 40 participants were included, of which 39 completed the trial. The observed differences between simvastatin and placebo groups in the primary outcomes, DNA and RNA oxidation, were small and nonsignificant (p=0.68), specifically, 3% in the simvastatin group compared to 7.1% in the placebo group for DNA oxidation and 7.3% in the simvastatin group compared to 3.4% in the placebo group. The differences in biomarkers related to plasma were not statistically significant between the treatments groups, with the exception of total vitamin E levels, which, as expected, were reduced in parallel with the reduction in plasma cholesterol. In healthy young male volunteers, short-term simvastatin treatment, which considerably reduces cholesterol, does not lead to a clinically relevant reduction in a panel of measures of oxidative stress. Whether simvastatin has effects on oxidative stress in diseased populations, such as diabetes or hemochromatosis, where oxidative stress is prominent, is unknown but seems unlikely.