We systematically characterized the oxidative metabolites of 17beta-estradiol and estrone formed by 15 human cytochrome P450 (CYP) isoforms. CYP1A1 had high activity for 17beta-estradiol 2-hydroxylation, followed by 15alpha-, 6alpha-, 4-, and 7alpha-hydroxylation. However, when estrone was the substrate, CYP1A1 formed more 4-hydroxyestrone than 15alpha- or 6alpha-hydroxyestrone, with 2-hydroxyestrone as the major metabolite. CYP1A2 had the highest activity for the 2-hydroxylation of both 17beta-estradiol and estrone, although it also had considerable activity for their 4-hydroxylation (9-13% of 2-hydroxylation). CYP1B1 mainly catalyzed the formation of catechol estrogens, with 4-hydroxyestrogens predominant. CYP2A6, 2B6, 2C8, 2C9, 2C19, and 2D6 each showed a varying degree of low catalytic activity for estrogen 2-hydroxylation, whereas CYP2C18 and CYP2E1 did not show any detectable estrogen-hydroxylating activity. CYP3A4 had strong activity for the formation of 2-hydroxyestradiol, followed by 4-hydroxyestradiol and an unknown polar metabolite, and small amounts of 16alpha- and 16beta-hydroxyestrogens were also formed. The ratio of 4- to 2-hydroxylation of 17beta-estradiol or estrone with CYP3A4 was 0.22 or 0.51, respectively. CYP3A5 had similar catalytic activity for the formation of 2- and 4- hydroxyestrogens. Notably, CYP3A5 had an unusually high ratio of 4- to 2-hydroxylation of 17beta-estradiol or estrone (0.53 or 1.26, respectively). CYP3A4 and 3A5 also catalyzed the formation of nonpolar estrogen metabolite peaks (chromatographically less polar than estrone). CYP3A7 had a distinct catalytic activity for the 16alpha-hydroxylation of estrone, but not 17beta-estradiol. CYP4A11 had little catalytic activity for the metabolism of 17beta-estradiol and estrone. In conclusion, many human CYP isoforms are involved in the oxidative metabolism of 17beta-estradiol and estrone, with a varying degree of catalytic activity and distinct regioselectivity.

Objectives To estimate neuropathic sign/symptom rates with initiation of combination antiretroviral therapy (cART) in HIV-infected ART-naive patients, and to investigate risk factors for: peripheral neuropathy and symptomatic peripheral neuropathy (SPN), recovery from peripheral neuropathy/SPN after neurotoxic ART (nART) discontinuation, and the absence of peripheral neuropathy/SPN while on nART. Design AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trial participants who initiated cART in randomized trials for ART-naive patients were annually screened for symptoms/signs of peripheral neuropathy. ART use and disease characteristics were collected longitudinally. Methods Peripheral neuropathy was defined as at least mild loss of vibration sensation in both great toes or absent/hypoactive ankle reflexes bilaterally. SPN was defined as peripheral neuropathy and bilateral symptoms. Generalized estimating equation logistic regression was used to estimate associations. Results Two thousand, one hundred and forty-one participants were followed from January 2000 to June 2007. Rates of peripheral neuropathy/SPN at 3 years were 32.1/8.6% despite 87.1% with HIV-1RNA 400 copies/ml or less and 70.3% with CD4 greater than 350 cells/µl. Associations with higher odds of peripheral neuropathy included older patient age and current nART use. Associations with higher odds of SPN included older patient age, nART use, and history of diabetes mellitus. Associations with lower odds of recovery after nART discontinuation included older patient age. Associations with higher odds of peripheral neuropathy while on nART included older patient age and current protease inhibitor use. Associations with higher odds of SPN while on nART included older patient age, history of diabetes, taller height, and protease inhibitor use. Conclusion Signs of peripheral neuropathy remain despite virologic/immunologic control but frequently occurs without symptoms. Aging is a risk factor for peripheral neuropathy/SPN.

Although widely cited as strong evidence that sexual selection has shaped human facial-attractiveness judgments, findings suggesting that women’s preferences for masculine characteristics in men’s faces are related to women’s hormonal status are equivocal and controversial. Consequently, we conducted the largest-ever longitudinal study of the hormonal correlates of women’s preferences for facial masculinity (N = 584). Analyses showed no compelling evidence that preferences for facial masculinity were related to changes in women’s salivary steroid hormone levels. Furthermore, both within-subjects and between-subjects comparisons showed no evidence that oral contraceptive use decreased masculinity preferences. However, women generally preferred masculinized over feminized versions of men’s faces, particularly when assessing men’s attractiveness for short-term, rather than long-term, relationships. Our results do not support the hypothesized link between women’s preferences for facial masculinity and their hormonal status.

The strength of sexual selection on secondary sexual traits varies depending on prevailing economic and ecological conditions. In humans, cross-cultural evidence suggests women’s preferences for men’s testosterone dependent masculine facial traits are stronger under conditions where health is compromised, male mortality rates are higher and economic development is higher. Here we use a sample of 4483 exclusively heterosexual women from 34 countries and employ mixed effects modelling to test how social, ecological and economic variables predict women’s facial masculinity preferences. We report women’s preferences for more masculine looking men are stronger in countries with higher sociosexuality and where national health indices and human development indices are higher, while no associations were found between preferences and indices of intra-sexual competition. Our results show that women’s preferences for masculine faces are stronger under conditions where offspring survival is higher and economic conditions are more favorable.

When choosing a mate, women are thought to face a trade-off between genetic and parental quality. Recent research suggests that this trade-off is influenced by environmental factors such as pathogen prevalence and resource scarcity, which affect the relative value of genetic and parental quality to offspring fitness. To further investigate these findings, the current study primed 60 women with pathogen prevalence, resource scarcity or an irrelevant threat, before administering a forced trade-off task that assessed mate preferences for traits thought to be indicative of genetic or parental quality. Women primed with pathogen prevalence revealed greater preferences for traits indicative of genetic quality at the expense of traits indicative of parental quality. The reverse was found for women primed with resource scarcity. These findings suggest that environmental factors may directly influence women's mate preferences owing to evolved plasticity, such that mate preferences are flexible in response to environmental factors.