No observed bidirectional effect between tenofovir diphosphate concentrations and gender-affirming hormone concentrations among transgender persons switching from tenofovir disoproxil fumarate/emtricitabine to tenofovir alafenamide/emtricitabine for HIV pre-exposure prophylaxis.

AIMS: Many transgender and gender diverse (TGD) individuals have expressed concerns about the potential for oral pre-exposure prophylaxis to affect hormonal concentrations achieved from taking gender-affirming hormone therapy (GAHT). The purpose of this study was to understand the bidirectional effects between hormone and intraerythrocytic tenofovir diphosphate concentrations when switching from tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) to tenofovir alafenamide/emtricitabine (TAF/FTC) in TGD users/nonusers of GAHT. METHODS: The study evaluated stored blood samples and dried blood spot cards from TGD adults without HIV who took ≥12 weeks of TDF/FTC and then switched to ≥12 weeks of TAF/FTC for pre-exposure prophylaxis. RESULTS: Thirty-nine individuals met the study inclusion criteria. Regardless of sex assigned at birth and the use of GAHT, there were no significant differences in hormone concentrations when individuals taking GAHT were taking TDF/FTC and then switched to TAF/FTC. Further, there was no significant difference in intraerythrocytic tenofovir diphosphate concentrations between users and nonusers of GAHT. CONCLUSION: There are no bidirectional effects between hormone and intraerythocytic tenofovir diphosphate concentrations when switching from TDF/FTC to TAF/FTC in TGD users/nonusers of GAHT.

Alcohol and breast cancer risk among Asian-American women in Los Angeles County.

INTRODUCTION: The role of alcohol and breast cancer risk in Asians has not been well studied. Recent studies suggest that even moderate alcohol intake may be associated with an increase in breast cancer risk, and this may be particularly relevant as alcohol intake is traditionally low among Asians. METHODS: We investigated the association between lifetime alcohol intake (including frequency, quantity, duration, timing, and beverage type) and breast cancer in a population-based case-control study of 2,229 Asian Americans diagnosed with incident breast cancer and 2,002 matched control women in Los Angeles County. Additionally, we examined the relation between current alcohol intake and serum concentrations of sex-hormones and growth factors in a subset of postmenopausal control women. RESULTS: Regular lifetime alcohol intake was significantly higher in US-born than non-US-born Asian Americans (P < 0.001) and almost twice as common in Japanese- than in Chinese- and Filipino-Americans (P < 0.001). Breast cancer risk increased with increasing alcohol intake among US-born Asian Americans; the odds ratios (ORs) per 5 grams per day and per 10 years of drinking were 1.21 (95% confidence interval (CI) 1.00 to 1.45) and 1.12 (95% CI, 0.98 to 1.28), respectively. Regular alcohol intake was a significant risk factor for Japanese-, but not for Chinese- and Filipino-Americans. Current consumers compared with nondrinkers showed lower concentrations of insulin-like growth factor binding protein 3 (P = 0.03) and nonsignificantly higher concentrations of estrone and androgens. CONCLUSIONS: Regular lifetime alcohol intake is a significant breast cancer risk factor in US-born Asian Americans and Japanese Americans, emphasizing the importance of this modifiable lifestyle factor in traditionally low-risk populations.

Effect of exercise on serum sex hormones in men: a 12-month randomized clinical trial.

PURPOSE: The effect of exercise on androgens in middle-aged to older men is poorly understood, and it could have implications for several aspects of health. This analysis was conducted to examine the effects of long-term aerobic exercise on serum sex hormones in middle-aged to older men. METHODS: One hundred two sedentary men, ages 40-75 yr, were randomly assigned to a 12-month exercise intervention or a control group (no change in activity). The combined facility- and home-based exercise program consisted of moderate/vigorous-intensity aerobic activity for 60 min.d(-1), 6 d.wk(-1). Serum concentrations of testosterone, free testosterone, dihydrotestosterone (DHT), 3alpha-androstanediol glucuronide (3alpha-Diol-G), estradiol, free estradiol, and sex hormone-binding globulin (SHBG) were measured at baseline, 3, and 12 months. RESULTS: Exercisers trained a mean of 370 min.wk(-1) (102% of goal), with only two dropouts. Cardiopulmonary fitness (.VO(2max)) increased 10.8% in exercisers and decreased by 1.8% in controls (P < 0.001). DHT increased 14.5% in exercisers versus 1.7% in controls at 3 months (P = 0.04); at 12 months, it remained 8.6% above baseline in exercisers versus a 3.1% decrease in controls (P = 0.03). SHBG increased 14.3% in exercisers versus 5.7% in controls at 3 months (P = 0.04); at 12 months, it remained 8.9% above baseline in exercisers versus 4.0% in controls (P = 0.13). There were significant trends toward increasing DHT and SHBG, with greater increases in .VO(2max) at 3 and 12 months in exercisers. No statistically significant differences were observed for testosterone, free testosterone, 3alpha-Diol-G, estradiol, or free estradiol in exercisers versus controls. CONCLUSIONS: A year-long, moderate-intensity aerobic exercise program increased DHT and SHBG, but it had no effect on other androgens in middle-aged to older men.

Oral Contraceptives and Multiple Sclerosis/Clinically Isolated Syndrome Susceptibility.

BACKGROUND: The incidence of multiple sclerosis (MS) is rising in women. OBJECTIVE: To determine whether the use of combined oral contraceptives (COCs) are associated with MS risk and whether this varies by progestin content. METHODS: We conducted a nested case-control study of females ages 14-48 years with incident MS or clinically isolated syndrome (CIS) 2008-2011 from the membership of Kaiser Permanente Southern California. Controls were matched on age, race/ethnicity and membership characteristics. COC use up to ten years prior to symptom onset was obtained from the complete electronic health record. RESULTS: We identified 400 women with incident MS/CIS and 3904 matched controls. Forty- percent of cases and 32% of controls had used COCs prior to symptom onset. The use of COCs was associated with a slightly increased risk of MS/CIS (adjusted OR = 1.52, 95%CI = 1.21-1.91; p<0.001). This risk did not vary by duration of COC use. The association varied by progestin content being more pronounced for levenorgestrol (adjusted OR = 1.75, 95%CI = 1.29-2.37; p<0.001) than norethindrone (adjusted OR = 1.57, 95%CI = 1.16-2.12; p = 0.003) and absent for the newest progestin, drospirenone (p = 0.95). CONCLUSIONS: Our findings should be interpreted cautiously. While the use of some combination oral contraceptives may contribute to the rising incidence of MS in women, an unmeasured confounder associated with the modern woman's lifestyle is a more likely explanation for this weak association.