Androgens and the breast

Abstract There is increasing interest in the role of androgens in the treatment of women but little is known about their long-term safety. There are also very few studies on testosterone therapy and breast cancer risk. However, some observations support the concept that androgens may counteract the stimulatory effects of estrogen and progestogen in the mammary gland. Mammographic breast density and breast cell proliferation could be regarded as surrogate markers for the risk of breast cancer. Recently the addition of testosterone to a common estrogen/progestogen regimen was found to inhibit the stimulatory effects of hormones on breast cell proliferation. The effects of testosterone alone on the postmenopausal breast remain to be investigated. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Androgens; Breast; Cancer Numerous women all over the world are treated with different combinations of estrogen and progestogen for hormonal contraception and the alleviation of menopausal symptoms. Currently, there is much confusion and an intense discussion about the longterm safety of such hormone therapy. In particular, the effects on the breast have been focused. Clinical and observational studies have reported an increased risk for breast cancer during postmenopausal combined estrogen/progestogen treatment (HT) The fact that sex steroid hormones and their receptors act in concert has stimulated interest in the role of androgens and testosterone in the treatment of women. The androgen receptor (AR) is a third member of the nuclear receptor super family and is a ligand-activated nuclear transcription factor which mediates androgen E-mail address: [email protected]. action The most obvious indication for androgen replacement therapy is symptomatic androgen insufficiency caused by pituitary, adrenal or ovarian failure. In many countries, testosterone treatment has gradually become a more accepted component of HT, especially in oophorectomized women. The testosterone therapy can also be considered in young women with premature ovarian failure, e.g., the Turner syndrome, after chemo or radiotherapy or in hypothalamic/pituitary disorders

Different effects of tibolone and continuous combined estrogen plus progestogen hormone therapy on sex hormone binding globulin and free testosterone levels -an association with mammographic density

Abstract Objective To compare the effects of tibolone and continuous combined hormone therapy on circulating sex steroids and their binding proteins and their relationship to mammographic density. Study design A prospective, double-blind placebo-controlled study. A total of 166 postmenopausal women were equally randomized to receive tibolone 2.5 mg, estradiol 2 mg/norethisterone acetate 1 mg (E2/NETA) or placebo. Serum analyses of sex steroids, insulin-like growth factor (IGF-I) and binding proteins and assessment of mammographic breast density were performed at baseline and after 6 months of treatment. Results Estrogens were markedly increased and androgens decreased by E2/NETA. In contrast, tibolone had only a minor influence on circulating estrogens. Sex hormone binding globulin (SHBG) levels were reduced by 50%, while levels of androgens increased. Baseline values of estrone sulfate (E1S), around 1.0-1.1 nmol/l, were increased to 44.7 nmol/l by E2/ NETA and to only 1.7 nmol/l by tibolone (p 5 0.001). Mammographic breast density displayed a negative correlation with age and body mass index and a positive association with SHBG. After 6 months there was also a negative correlation with levels of free testosterone. Conclusion We found that tibolone and E2/NETA caused distinct differences in estrogen/androgen status and blood levels of possible breast mitogens. The negative association between free testosterone and mammographic density could be a possible explanation for tibolone having less influence on the breast

Studies on PZ, the pregnancy zone protein

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Metabolism of estrone sulfate by normal breast tissue : Influence of menopausal status and oral contraceptives

The metabolism of [ 3 H]estrone sulfate ([ 3 H]E 1 S) was studied in normal breast tissue from 10 premenopausal women without oral contraceptives (OC), in 12 OC users and in 9 untreated postmenopausal women. [ 3 H]E 1 S was converted into estrone ([ 3 H]E 1 ) and estradiol-17β ([ 3 H]E 2 ) by tissue samples from all three groups of women, with only minor formation of other unconjugated compounds. The rate of [ 3 H]E 2 formation was significantly higher in premenopausal women without OC than in postmenopausal women. Among premenopausal women, OC users had a significantly lower rate of total hydrolysis and of [ 3 H]E 1 formation than non-users. The rate of total hydrolysis of [ 3 H]E 1 S in normal breast tissue from all three groups of women was similar to that in muscle, but the rate of [ 3 H]E 2 formation was ten times higher. Both total hydrolysis rate and rate of [ 3 H]E 2 formation were significantly lower in normal breast tissue than in breast carcinoma and in normal and neoplastic endometrium. The specific ability of normal breast tissue to convert E 1 S into the terminal biologically active estrogen E 2 may be important for estrogenic stimulation of the breast in subjects with low circulating E 2 levels. The lower rate of E 1 formation in OC users may reflect an inhibitory effect of the progestagen compound in such preparations

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 an effect for sixteen of the eighteen total regressions we run. The two regression specifications which are 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.JEL codes: C91,D0

Effects of oral contraceptives on body composition and physical performance in female athletes.

Menstrual disturbances are common among female athletes, and oral contraceptives (OCs) are often recommended as estrogen substitution. However, there is little information about the effects of OC use in athletes, and there is great concern that OCs might impair physical performance. The aim of this study was to investigate the effects of OC use on body composition and physical performance in female athletes. Twenty-six endurance athletes (13 with oligo-/amenorrhea and 13 regularly menstruating athletes) and 12 sedentary controls were examined before and after 10 months of treatment with a low dose, monophasic, combined OC. Significant changes in body composition were recorded in the athletes, but not in the controls. There was an increase in weight and fat mass only in athletes with oligo-/amenorrhea. These changes were associated with a decrease in ovarian androgens. OC treatment also increased bone mineral density, with the largest increase in athletes with a low bone mineral density at baseline. Despite significant changes in body composition, little impact on physical performance was recorded. We have demonstrated that OC treatment in female athletes has predominantly beneficial effects on body composition without adverse effects on physical performance and could be used for the prevention of osteoporosis in athletic amenorrhea. However, it cannot be excluded that a marked increase in fat mass might have unfavorable effects for athletic performance in individual women

Hormonal contraceptives do not impact economic preferences: Evidence from a randomized trial

A growing body of correlational studies suggests that sex hormones such as those contained in, or affected by, oral contraceptives (OCs) may impact economic behavior. However, despite widespread use of OCs among women in Western countries, little is known about their potential behavioral effects. The present study investigates whether OCs causally influence economic preferences. We randomly allocate 340 women aged 18–35 to three months of a widely used OC or placebo treatment. At the end of treatment, we conduct an economic experiment measuring altruism, financial risk taking, and willingness to compete. The statistical power is 80% to detect an effect size equal to a Cohen’s d of 0.30 at the 5% level. We find no significant effects of OCs on any of the measured preferences, indicating that this widely used OC treatment, commonly used throughout the world, does not significantly affect the measured economic preferences. Further, we find no relation between menstrual cycle phase and economic preferences in the placebo group.ISSN:0025-1909ISSN:1526-550