The digit ratio (2D:4D) and economic preferences: no robust associations in a sample of 330 women.

Many studies report on the association between 2D:4D, a putative marker for prenatal testosterone exposure, and economic preferences. However, most of these studies have limited sample sizes and test multiple hypotheses (without preregistration). In this study we mainly replicate the common specifications found in the literature for the association between the 2D:4D ratio and risk taking, the willingness to compete, and dictator game giving separately. In a sample of 330 women we find no robust associations between any of these economic preferences and 2D:4D. We find no evidence of a statistically significant relation for 16 of the 18 total regressions we run. The two regression specifications which are statistically significant have not previously been reported and the associations are not in the expected direction, and therefore they are unlikely to represent a real effect.

A first-choice combined oral contraceptive influences general well-being in healthy women: a double-blind, randomized, placebo-controlled trial.

OBJECTIVE: To determine whether there is a causal effect of oral contraceptive (OC) treatment on general well-being and depressed mood in healthy women. DESIGN: Double-blind, randomized, and placebo-controlled trial. SETTING: University hospital. PATIENT(S): Three hundred and forty healthy women aged 18-35 years randomized to treatment, of whom 332 completed the data collection at follow-up evaluation. INTERVENTION(S): A combined OC (150 µg levonorgestrel and 30 µg ethinylestradiol) or placebo for 3 months of treatment. MAIN OUTCOME MEASURE(S): Primary outcome measures: global score of Psychological General Well-Being Index (PGWBI) and the Beck Depression Inventory (BDI); secondary outcome measures: six separate dimensions of the PGWBI. RESULT(S): The OC treatment statistically significantly decreased general well-being compared with placebo -4.12 (95% CI, -7.18 to -1.06). Furthermore, OC decreased the following PGWBI dimensions compared with placebo: positive well-being -3.90 (95% CI, -7.78 to -0.01), self-control -6.63 (95% CI, -11.20 to -2.06), and vitality -6.84 (95% CI, -10.80 to -2.88). The effect of OC on depressive symptoms and on the PGWBI dimension depressed mood were not statistically significant. CONCLUSION(S): This study demonstrates a statistically significant reduction in general well-being by a first-choice OC in comparison with placebo in healthy women. We found no statistically significant effects on depressive symptoms. A reduction in general well-being should be of clinical importance.

Combined Oral Contraceptives and Sexual Function in Women-a Double-Blind, Randomized, Placebo-Controlled Trial.

CONTEXT: There is a lack of knowledge about how oral contraceptives may affect sexual function. OBJECTIVE: To determine whether there is a causal effect of oral contraceptives on sexuality. We hypothesized that a widely used pill impairs sexuality. DESIGN: A double-blind, randomized, placebo-controlled trial. Enrollment began in February 2012 and was completed in August 2015. SETTING: Karolinska University Hospital, Stockholm, Sweden. PARTICIPANTS: A total of 340 healthy women, aged 18-35 years, were randomized to treatment, and 332 completed the study. INTERVENTIONS: A combined oral contraceptive (150 µg levonorgestrel and 30 µg ethinylestradiol) or placebo for 3 months of treatment. MAIN OUTCOME MEASURES: The primary outcome was the aggregate score on the Profile of Female Sexual Function (PFSF). Secondary outcomes were the seven domains of the PFSF, the Sexual Activity Log, and the Personal Distress Scale. RESULTS: Overall sexual function was similar in women in the oral contraceptive and placebo groups. The PFSF domains desire (-4.4; 95% confidence interval [CI], -8.49 to -0.38; P = .032), arousal (-5.1; 95% CI, -9.63 to -0.48; P = .030), and pleasure (-5.1; 95% CI, -9.97 to -0.32; P = .036) were significantly reduced in comparison to placebo, whereas orgasm, concern, responsiveness, and self-image were similar between groups. The mean frequency of satisfying sexual episodes and personal distress were also similar between groups. CONCLUSIONS: This study shows no negative impact of a levonorgestrel-containing oral contraceptive on overall sexual function, although three of seven sexual function domains were adversely affected.

Sex hormone levels as determinants of bone mineral density and osteoporosis in Vietnamese women and men.

This study sought to investigate the prevalence of osteoporosis and the role of sex hormone levels in the determination of bone mineral density (BMD) and osteoporosis in a Vietnamese population of women and men. The cross-sectional study involved 269 women and 222 men aged 13-83 years, who were randomly selected from urban and rural areas in northern Vietnam. Serum concentrations of estradiol and testosterone were analyzed, and BMD was measured by dual X-ray absorptiometry. We found that the prevalence of osteoporosis in postmenopausal women was 18, 17, and 37 % for the femoral neck, total hip, and lumbar spine, respectively. For men aged 50 years or older, the corresponding values were 8, 7, and 12 %. In men, the most important predictors of BMD for the femoral neck and total hip were age, body mass index, and serum levels of estradiol. For the BMD of the lumbar spine, testosterone also had a significant influence. Determinants of osteoporosis in men for the total hip and lumbar spine were age, weight, and serum concentrations of estradiol and testosterone. In postmenopausal women, age, weight, and residence (urban vs rural) were the most important predictors of BMD and osteoporosis. For all women (including those of reproductive age), serum levels of estradiol were also significant. These data suggest that the prevalence of osteoporosis in the Vietnamese population is high also in men, and that estradiol levels are essential for bone mass in both men and women. The results should have clinical implications and increase awareness of an important health issue within Vietnamese society.

ISGE statement on oral emergency contraception.

Unintended pregnancy is an important public health problem worldwide. Unwanted pregnancies may end in induced abortion (legal or illegal, safe or unsafe) or in childbirth. In many parts of the world both can be life threatening. Even where both are safe, abortion is distressing for all concerned while unwanted births often lead to poor health and social outcomes for both the mother and her child.

Cognitive function in association with sex hormones in postmenopausal women.

Several studies have suggested gender differences in cognitive function, but data on the association between sex hormones and cognitive function are contradictory. The aim of our randomized double-blind study was to explore the possible relations between cognitive function and serum levels of sex hormones, oxytocin and insulin-like growth factor-I (IGF-I) in postmenopausal women. Two-hundred healthy postmenopausal women were randomly assigned to receive estrogen, testosterone or placebo treatment for 1 month. The associations of spatial ability, verbal fluency and verbal memory with serum levels of estradiol, testosterone, estradiol/testosterone ratio, androstanediol, oxytocin and IGF-I were analyzed. Spatial ability showed a negative correlation with serum estradiol, estradiol/testosterone ratio, oxytocin levels and a positive association with androstanediol levels. Verbal fluency displayed a negative relationship with serum levels of testosterone, IGF-I and a positive with estradiol/testosterone ratio. Verbal memory displayed a positive correlation to androstanediol. Data suggest that not only absolute levels of sex hormones but also the balance between estrogen and testosterone and their metabolites may be important for cognitive function in women.

Effect of estrogen and testosterone replacement therapy on cognitive fatigue.

Both estrogen and testosterone insufficiency has been associated with reduced psychological well-being including fatigue. However, hormonal replacement studies on fatigue are rare. Therefore, we wanted to study the effect of testosterone and estrogen replacement therapy on cognitive fatigue and the relation between sex hormone levels and cognitive fatigue in oophorectomized women. Fifty women with surgically induced menopause (mean age: 54.0 ± 2.9 years) were randomly assigned to treatment with estradiol valerate in combination with testosterone undecanoate or placebo for 24 weeks in a double-blind cross-over study. Neuropsychological tests and questionnaires were used to assess cognitive fatigue and psychological well-being. Cognitive fatigue was significantly associated to poor self-rated health and higher body mass index but not to general psychological well-being or sex hormone levels. Treatment with testosterone + estrogen had no significant effect on cognitive fatigue but the results indicated a curvilinear relation for hormonal levels. The estrogen/testosterone ratio was more related to functions rather than high or low hormone levels per se. We found that cognitive fatigue is frequent in oophorectomized women and negatively associated to self-perceived health and positively associated to BMI. A well-balanced ratio between estrogen and testosterone levels may be important for cognitive fatigue.

Vitamin D deficiency in northern Vietnam: prevalence, risk factors and associations with bone mineral density.

PURPOSE: Vitamin D deficiency has been linked to osteoporosis and also to the risk of cancer, autoimmune disorders and cardiovascular diseases. This study sought to determine the prevalence of, and risk factors for, vitamin D deficiency and its relationship with bone mineral density (BMD) in a Vietnamese population. METHODS: This cross-sectional study involved 269 women and 222 men aged 13-83 years, who were randomly selected from urban and rural areas in northern Vietnam. Serum concentrations of 25-hydroxy-vitamin D [25(OH)D] and parathyroid hormone (PTH) were measured by electrochemiluminescence immunoassay. Vitamin D deficiency was defined as serum 25(OH)D levels below 20 ng/mL. BMD was measured by dual X-ray absorptiometry. RESULTS: The prevalence of vitamin D deficiency in women was 30%, almost two-fold higher than in men (16%). Significant predictors of vitamin D deficiency in women were urban residency (p<0.01) and age less than 30 years (p<0.01), whereas use of contraceptive pills was protective (p<0.01). In men, winter season was the only significant predictor of vitamin D deficiency (p<0.01). In multiple linear regression analysis, serum levels of 25(OH)D were positively associated with BMD in both women (p<0.001) and men (p<0.001). CONCLUSIONS: These data suggest that the prevalence of vitamin D deficiency is high in the Vietnamese population, and that part of this prevalence could be explained by low exposure to sunlight (urban residency and winter season). The high prevalence of vitamin D deficiency should raise the awareness of potentially important health issues such as osteoporosis within the Vietnamese society.

Low aglycone content in commercial soy drink products.

The effectiveness of soy isoflavones to prevent bone loss in postmenopausal women is controversial. While consumption of soy in Vietnam is very high, we recently reported a prevalence of osteoporosis comparable to that of many Western populations. In the present study, we analyzed the isoflavone content of soy drink products commercially available in Vietnam and Sweden, and we also compared these products to "home-made" soy drink from beans of different origin. The amounts of the bioactive aglycones (daidzein, glycitein and genistein) and their glycoside isomers were quantified by high-pressure liquid chromatography. We found that the total isoflavone content was low in all preparations, around 70-100 mg/L and of this only 10% were bioactive aglycones. Of these, the Vietnamese products contained significantly lower levels of glycitein than the products from Sweden and "home-made" soy drink preparations. The results show that consumption of several liters of soy drink per day would be needed to achieve threshold levels for a protective effect on bone. There was no significant association between total protein and isoflavone content in different products. Accurate labeling of soy drink and other products eg of aglycone and glycoside content would allow health professionals and researchers to better explore the possible benefits of soy in dietary intervention studies.

Distribution of cyclooxygenases 1 and 2 in the uterus and breast of cynomolgus monkeys-effects of hormone treatment.

OBJECTIVE: The aim of this study was to compare the distribution and immunoreactivity of cyclooxygenase (COX) 1 and COX-2 in normal uterus and breast after long-term hormone therapy in postmenopausal monkeys. METHODS: Female adult cynomolgus macaques were bilaterally ovariectomized 3 months before the initiation of hormone treatment. The animals were either treated (experiment 1) with conjugated equine estrogens (CEE), medroxyprogesterone acetate (MPA), CEE + MPA, or tamoxifen or designated as controls (C). In experiment 2, the animals were either treated with CEE, CEE + MPA, or tibolone or designated as C. Breast tissue and uteri were collected, fixed, and paraffin embedded. Immunohistochemistry assays for COX-1 and COX-2 were performed. RESULTS: COX-1 immunostaining was decreased by tamoxifen and CEE treatment in the endometrial stroma and by CEE + MPA in the myometrium. COX-1 immunostaining of the breast epithelia was down-regulated by CEE + MPA, whereas other cell types in the breast seem to be less affected by hormone treatment.COX-2 immunoreactivity in the endometrial stroma was increased by CEE + MPA. In the glandular epithelium, CEE + MPA and tibolone treatment increased COX-2 immunostaining compared with CEE treatment only and no treatment at all (C). No effect from hormone treatment on COX-2 immunostaining was found in the myometrium. COX-2 immunostaining in the glandular epithelium of the breast was, in experiment 2, increased after CEE treatment compared with no treatment (C). No other effects by hormone therapy on COX-2 expression were found in the breast. CONCLUSIONS: Our results show that COX-1 and COX-2 are differently distributed and regulated by hormones in the normal uterus and breast of ovariectomized macaques. COX-1 is prevailing in the uterus, whereas COX-2 is dominant in the mammary gland.

A randomized trial of the effect of testosterone and estrogen on verbal fluency, verbal memory, and spatial ability in healthy postmenopausal women.

OBJECTIVE: To test the causal relationship between sex hormones and cognitive skills in postmenopausal women. We hypothesized that testosterone would decrease verbal memory and verbal fluency and increase spatial ability compared with a placebo. For estrogen, we conversely hypothesized that the treatment would increase verbal fluency and verbal memory and decrease spatial ability. DESIGN: Randomized, double-blind, placebo-controlled, parallel-group trial. SETTING: Women's health clinical research unit at a university hospital. PATIENT(S): Two-hundred healthy, naturally postmenopausal women aged 50-65 years. INTERVENTION(S): Randomization to 4 weeks' treatment with testosterone (testosterone undecanoate, 40 mg/day), estrogen (oral E2 2 mg/day) or placebo. MAIN OUTCOME MEASURE(S): Comparisons in verbal fluency, verbal memory, and spatial ability between the three treatment groups. RESULT(S): We found no significant effects of testosterone or estrogen on verbal fluency, verbal memory, or spatial ability. CONCLUSION(S): Our results give no support for short-term testosterone or estrogen treatment having any substantial effect on verbal fluency, verbal memory, or spatial ability in healthy postmenopausal women.

The effect of transdermal testosterone on mammographic density in postmenopausal women not receiving systemic estrogen therapy.

CONTEXT: Greater mammographic density is associated with increased breast cancer risk and reduced diagnostic mammographic sensitivity and may be seen with estrogen/progestin therapy (EPT). The effects of testosterone therapy on mammographic density in postmenopausal women not on EPT are not known. OBJECTIVE: Our objective was to compare effects of two doses of the testosterone transdermal patch (TTP) with placebo in postmenopausal women without concomitant EPT on mammographic density over 52 wk. DESIGN: We conducted a randomized, double-blind, placebo-controlled, parallel-group, multinational trial. PATIENTS: Patients included 279 postmenopausal women participating in a testosterone and sexual function study with paired mammograms for baseline and 52 wk/exit. INTERVENTIONS: Patients were randomized to placebo, TTP 150 microg/d, or TTP 300 microg/d, stratified by menopause type (natural or surgical). MAIN OUTCOME MEASURES: Change from baseline to wk 52 in the percentage of dense tissue (PD) on digital mammograms. RESULTS: A total of 250 women with paired mammograms for study baseline and wk 52 were included in the primary analysis. Mean age was 54.6 yr, baseline body mass index was 27.5 kg/m(2), and 78% were naturally menopausal. There were no baseline differences between groups. Mean changes from baseline (+/-SEM) in PD for placebo, TTP 150 microg/d and TTP 300 microg/d were small (0.05 +/- 0.16, 0.06 +/- 0.19, and 0.21 +/- 0.17%) and not significantly different. There were no statistically significant differences from placebo for total dense or nondense area and no significant relationships between hormone levels and PD after adjustment for body mass index. CONCLUSION: TTP therapy over 52 wk appears to have no significant effect on digitally quantified absolute or percent dense mammographic area in postmenopausal women not using EPT.

A randomized trial of the effect of estrogen and testosterone on economic behavior.

Existing correlative evidence suggests that sex hormones may affect economic behavior such as risk taking and reciprocal fairness. To test this hypothesis we conducted a double-blind randomized study. Two-hundred healthy postmenopausal women aged 50-65 years were randomly allocated to 4 weeks of treatment with estrogen, testosterone, or placebo. At the end of the treatment period, the subjects participated in a series of economic experiments that measure altruism, reciprocal fairness, trust, trustworthiness, and risk attitudes. There was no significant effect of estrogen or testosterone on any of the studied behaviors.

Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: a double-blind, randomised, non-inferiority trial.

BACKGROUND: Vasomotor symptoms and bone loss are complications frequently induced by adjuvant treatment for breast cancer. Tibolone prevents both side-effects, but its effect on cancer recurrence is unknown. The aim of this study was to show non-inferiority of tibolone to placebo regarding risk of recurrence in breast-cancer patients with climacteric complaints. METHODS: Between July 11, 2002, and Dec 20, 2004, women surgically treated for a histologically confirmed breast cancer (T(1-3)N(0-2)M(0)) with vasomotor symptoms were randomly assigned to either tibolone 2.5 mg daily or placebo at 245 centres in 31 countries. Randomisation was done by use of a centralised interactive voice response system, stratified by centre, with a block size of four. The primary endpoint was breast-cancer recurrence, including contralateral breast cancer, and was analysed in the intention-to-treat (ITT) and per-protocol populations; the margin for non-inferiority was set as a hazard ratio of 1.278. This study is registered with ClinicalTrials.gov, number NCT00408863. FINDINGS: Of the 3148 women randomised, 3098 were included in the ITT analysis (1556 in the tibolone group and 1542 in the placebo group). Mean age at randomisation was 52.7 years (SD 7.3) and mean time since surgery was 2.1 years (SD 1.3). 1792 of 3098 (58%) women were node positive and 2185 of 3098 (71%) were oestrogen-receptor positive. At study entry, 2068 of 3098 (67%) women used tamoxifen and 202 of 3098 (6.5%) women used aromatase inhibitors. The mean daily number of hot flushes was 6.4 (SD 5.1). After a median follow-up of 3.1 years (range 0.01-4.99), 237 of 1556 (15.2%) women on tibolone had a cancer recurrence, compared with 165 of 1542 (10.7%) on placebo (HR 1.40 [95% CI 1.14-1.70]; p=0.001). Results in the per-protocol population were similar (209 of 1254 [16.7%] women in the tibolone group had a recurrence vs 138 of 1213 [11.4%] women in the placebo group; HR 1.44 [95% CI 1.16-1.79]; p=0.0009). Tibolone was not different from placebo with regard to other safety outcomes, such as mortality (72 patients vs 63 patients, respectively), cardiovascular events (14 vs 10, respectively), or gynaecological cancers (10 vs 10, respectively). Vasomotor symptoms and bone-mineral density improved significantly with tibolone, compared with placebo. INTERPRETATION: Tibolone increases the risk of recurrence in breast cancer patients, while relieving vasomotor symptoms and preventing bone loss. FUNDING: Schering-Plough (formerly NV Organon, Oss, Netherlands).

Breast cancer and hormonal therapy.

Valid evidence from randomized-controlled trials indicates that breast cancer risk is increased with combined estrogen/progestogen use and that such treatment implies a risk greater than that of estrogen alone. Overall, risk estimates from observational studies are somewhat higher than in randomized-controlled trials but remain modest as compared with other risk factors even after long-term treatment. For combined estrogen/progestogen therapy, risk increases gradually to reach statistical significance after 4 to 5 years. Apart from its many beneficial health effects, the safety data for use of estrogen alone are quite reassuring. The only justifications for progestogen addition are for bleeding control and endometrial protection. At present, there are several new therapeutic compounds and concepts in development, which hold promise to provide both endometrial protection and breast safety.

Estrogen and tibolone metabolite levels in blood and breast tissue of postmenopausal women recently diagnosed with early-stage breast cancer and treated with tibolone or placebo for 14 days.

Unlike estrogens plus progestagens, tibolone, a selective tissue estrogenic activity regulator, does not increase breast tenderness and mammographic density. To elucidate this, serum and breast levels of tibolone and estrogenic metabolites are measured. Postmenopausal women (n = 102) with early-stage, ER(+ve), primary breast cancer received tibolone or placebo for 14 days in an exploratory, double-blind, randomized trial (STEM carcinoma tissue). Baseline and presurgery sera were collected; tumor tissues were obtained at surgery. E(1) (estrone), E(2) (estradiol), E(1)S (estrone-sulfate), tibolone-its nonsulfated, monosulfated, and disulfated 3-hydroxymetabolites-and Delta(4)-tibolone were measured by validated gas chromatography and mass spectrometry and liquid chromatography with tandem mass spectrometry assays. More than 12 hours after the final dose, serum E(1), E(2), and E(1)S levels were unchanged with placebo, whereas tibolone significantly increased E(1)S and the E(1)S/(E(1) + E(2)) ratio. In tumors, E(1) and E(2) levels were higher than in serum, and E(1)S levels were lower, with placebo and tibolone administration. The percentage of E(1)S was about 90% in serum and 16% in tissue. Tibolone did not affect tissue levels of endogenous estrogens. Serum levels of estrogenic 3alpha- and 3beta-hydroxytibolone, progestagenic/androgenic Delta(4)-tibolone, and monosulfate metabolites were low. Serum 3alphaS,17betaS-tibolone and 3 betaS,17betaS-tibolone levels were 250 and 52 ng/mL, respectively. Tumor levels of 3alpha- and 3beta-hydroxytibolone and Delta(4)-tibolone were higher than in serum, but disulfate levels were lower. The percentage of sulfated tibolone metabolites was 99% in serum and 96% in tumor. Serum metabolite patterns of estradiol and tibolone are different from those in tissues and are compatible with neutral effects of tibolone on breast Ki67 expression.