Testosterone Exposure Research Articles

Prenatal and pubertal testosterone exposure imprint permanent modifications in the prostate that predispose to the development of lesions in old Mongolian gerbils.

The prostate is an accessory sex gland that develops under precise androgenic control. It is known that hormonal imbalance may disrupt its development predisposing this gland to develop diseases during aging. Although the hypothesis regarding earlier origins of prostate diseases was proposed many years ago, the mechanisms underlying this complex phenomenon are poorly understood. Therefore, the aim of this study was to evaluate the prostates of old male gerbils exposed to testosterone during intrauterine and postnatal life using morphological, biometrical, stereological, Kariometric, immunohistochemical, and immunofluorescence analyses. Our findings demonstrate that prenatal and pubertal exposure to testosterone increases the susceptibility to the development of prostate diseases during aging. The presence of a more proliferative gland associated with foci of adenomatous hyperplasia in animals exposed to testosterone during the prenatal and pubertal phase show that the utero life and the pubertal period are important phases for prostatic morphophysiology establishment, which is a determinant for the health of the gland during aging. Therefore, these findings reinforce the idea that prostate disease may result from hormonal disruptions in early events during prostate development, which imprint permanently on the gland predisposing it to develop lesions in later stages of life.

Effect of co-twin gender on neurodevelopmental symptoms: a twin register study.

BackgroundAutism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are neurodevelopmental disorders thought to have both genetic and environmental causes. It has been hypothesized that exposure to elevated levels of prenatal testosterone is associated with elevated traits of ASD and ADHD. Assuming that testosterone levels from a dizygotic male twin fetus may lead to enhanced testosterone exposure of its co-twins, we aimed to test the prenatal testosterone hypothesis by comparing same-sex with opposite-sex dizygotic twins with respect to neurodevelopmental symptoms.MethodsNeuropsychiatric traits were assessed in a population-based twin cohort from the Child and Adolescent Twin Study in Sweden (CATSS). Parental interviews were conducted for 16,312 dizygotic twins, 9 and 12 years old, with the Autism—Tics, ADHD, and other Comorbidities inventory (A-TAC).ResultsGirls with a female co-twin had an increased risk of reaching the cut-off score for ADHD compared with girls with a male co-twin. Both boys and girls with a female co-twin displayed a larger number of traits related to attention deficit and repetitive and stereotyped behaviors than those with a male twin. In girls, this also extended to social interaction and the combined measures for ASD and ADHD, however, with small effect sizes.ConclusionsOur results are reverse to what would have been expected from the prenatal testosterone hypothesis but consistent with a previous study of ASD and ADHD traits in dizygotic twins. The seemingly protective effect for girls of having a twin brother may be an effect of parent report bias, but may also be an unexpected effect of sharing the intrauterine environment with a male co-twin.

Perinatal testosterone exposure is critical for the development of the male-specific sexually dimorphic gastrin-releasing peptide system in the lumbosacral spinal cord that mediates erection and ejaculation.

BackgroundIn rats, a sexually dimorphic spinal gastrin-releasing peptide (GRP) system in the lumbosacral spinal cord projects to spinal centers that control erection and ejaculation. This system controls the sexual function of adult males in an androgen-dependent manner. In the present study, we assessed the influence of androgen exposure on the spinal GRP system during a critical period of the development of sexual dimorphism.MethodsImmunohistochemistry was used to determine if the development of the spinal GRP system is regulated by the perinatal androgen surge. We first analyzed the responses of neonates administered with anti-androgen flutamide. To remove endogenous androgens, rats were castrated at birth. Further, neonatal females were administered androgens during a critical period to evaluate the development of the male-specific spinal GRP system.ResultsTreatment of neonates with flutamide on postnatal days 0 and 1 attenuated the spinal GRP system during adulthood. Castrating male rats at birth resulted in a decrease in the number of GRP neurons and the intensity of neuronal GRP in the spinal cord during adulthood despite testosterone supplementation during puberty. This effect was prevented if the rats were treated with testosterone propionate immediately after castration. Moreover, treating female rats with androgens on the day of birth and the next day, masculinized the spinal GRP system during adulthood, which resembled the masculinized phenotype of adult males and induced a hypermasculine appearance.ConclusionsThe perinatal androgen surge plays a key role in masculinization of the spinal GRP system that controls male sexual behavior. Further, the present study provides potentially new approaches to treat sexual disorders of males.

Side-specific effect of yolk testosterone elevation on second-to-fourth digit ratio in a wild passerine.

Second-to-fourth digit ratio is a widely investigated sexually dimorphic morphological trait in human studies and could reliably indicate the prenatal steroid environment. Conducting manipulative experiments to test this hypothesis comes up against ethical limits in humans. However, oviparous tetrapods may be excellent models to experimentally investigate the effects of prenatal steroids on offspring second-to-fourth digit ratio. In this field study, we injected collared flycatcher (Ficedula albicollis) eggs with physiological doses of testosterone. Fledglings from eggs with elevated yolk testosterone, regardless of their sex, had longer second digits on their left feet than controls, while the fourth digit did not differ between groups. Therefore, second-to-fourth digit ratio was higher in the testosterone-injected group, but only on the left foot. This is the first study which shows experimentally that early testosterone exposure can affect second-to-fourth digit ratio in a wild population of a passerine bird.

Prenatal Testosterone and the Earnings of Men and Women

Testosterone, which induces sexual differentiation of the male fetus, is believed to transfer from males to their littermates in placental mammals. Among humans, individuals with a male twin have been found to exhibit greater masculinization of sexually dimorphic attributes relative to those with a female twin. We therefore regard twinning as a plausible natural experiment to test the link between prenatal exposure to testosterone and labor market earnings. For men, the results suggest positive returns to testosterone exposure. For women, however, the results indicate that prenatal testosterone does not generate higher earnings and may even be associated with modest declines.

Is digit ratio (2D:4D) a reliable pointer to speech laterality?

The relative length of the second and fourth digits (2D:4D ratio) is sexually dimorphic and a retrospective biomarker of prenatal hormonal exposure. Low ratios indicate higher prenatal testosterone (pT) and lower estrogen exposure, whereas the reverse pattern is associated with high ratios. Elevated levels of pT exposure have long been thought to modulate hemispheric specialisation; subsequently many studies use the 2D:4D ratio as a proxy index for pT to examine the effects of prenatal hormonal exposure on lateralised cognitive abilities. Here we used Transcranial Doppler ultrasonography and digit ratio to investigate whether pT has an influence on speech laterality. We tested 34 right and 14 left handed adults. Our results indicate that speech representation is unrelated to digit characteristics and therefore purportedly pT. We discuss these findings in relation to androgen theories of lateralisation.

Abstract C68: SLCO1B3 influences taxane-response in prostate cancer

Abstract Introduction: Castration resistant prostate cancer (CRPC) patients are treated with docetaxel as first-line chemotherapy. Unfortunately, response to docetaxel is highly variable among patients and intrinsic or acquired resistance is common. Understanding mechanisms of resistance may help to define biomarkers to select patients for the best therapy options and prevent treatments to which they may respond poorly. We established docetaxel-resistant xenografts from chemotherapy-naïve patient-derived xenografts (PDXs) in vivo. Next generation sequencing analysis of these chemotherapy-naïve and docetaxel-resistant PDXs revealed that SLCO1B3 expression was significantly downregulated in a subset of docetaxel-resistant tumors. As SLCO1B3 is also a known transporter of testosterone, the aim of the study was to further investigated its expression in relation with hormonal status of CRPC cells. Methods: Androgen responsive SLCO1B3 expressing PC346C cells were used to perform uptake assays with [14C]-labeled docetaxel and cabazitaxel after silencing of SLCO1B3 with siRNA. The androgen resistant PC346C-DCC-G clone, created by long-term culturing of PC346C cells in androgen deprived medium, did not express SLCO1B3. PC346C-DCC-G cells were stably transfected with SLCO1B3 or with a control construct containing green fluorescent protein (GFP). MTT cell proliferation assays were performed after 10 days of exposure to docetaxel or cabazitaxel in a dose range of 0-10nM. Prostate specific antigen (PSA) production was measured with an ELISA assay after exposure of 0.1nM testosterone for 30 minutes. Results: Silencing of SLCO1B3 in parental PC346C decreased uptake of docetaxel and cabazitaxel 2.0-fold (p = 0.01) and 2.1-fold (p = 0.0003), respectively. In line with this observation, SLCO1B3-transfected, overexpressing PC346C-DCC-G cells were more sensitive to docetaxel and cabazitaxel, resulting in reduced IC50-values of 1.9-fold for docetaxel and 3.5-fold for cabazitaxel compared to control transfected cells. Moreover, PSA production in SLCO1B3-overexpressing PC346C-DCC-G cells increased 2-fold as compared to control (p = 0.05) after testosterone exposure. Conclusion: Prostate cancer cells that overexpress SLCO1B3 are more sensitive to docetaxel and cabazitaxel treatment, which could be linked to increased uptake of both taxanes. Further studies are needed to clarify the role of SLCO1B3 in the uptake of cabazitaxel into the cell. Moreover, SLCO1B3 expression affects hormonal status of prostate cancer cells as reflected by PSA production. Research is ongoing to further elucidate the role of SLCO1B3 in prostate cancer and its impact on taxane efficacy and response. Citation Format: Ellen S. de Morree, Rene Bottcher, Robert J. van Soest, Ashraf Aghai, Corrina M. de Ridder, Alice A. Gibson, Ron HJ Mathijssen, Herman Burger, Erik AC Wiemer, Alex Sparreboom, Wytske M. van Weerden, Ronald de Wit. SLCO1B3 influences taxane-response in prostate cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C68.

Social communication and emotion difficulties and second to fourth digit ratio in a large community-based sample.

BackgroundRecent research investigating the extreme male brain theory of autism spectrum disorders (ASD) has drawn attention to the possibility that autistic type social difficulties may be associated with high prenatal testosterone exposure. This study aims to investigate the association between social communication and emotion recognition difficulties and second to fourth digit ratio (2D:4D) and circulating maternal testosterone during pregnancy in a large community-based cohort: the Avon Longitudinal Study of Parents and Children (ALSPAC). A secondary aim is to investigate possible gender differences in the associations.MethodsData on social communication (Social and Communication Disorders Checklist, N = 7165), emotion recognition (emotional triangles, N = 5844 and diagnostics analysis of non-verbal accuracy, N = 7488) and 2D:4D (second to fourth digit ratio, N = 7159) were collected in childhood and early adolescence from questionnaires and face-to-face assessments. Complete data was available on 3515 children. Maternal circulating testosterone during pregnancy was available in a subsample of 89 children.ResultsMales had lower 2D:4D ratios than females [t (3513) = −9.775, p < 0.001]. An association was found between measures of social communication and emotion recognition, and the lowest 10 % of 2D:4D ratios. A significant association was found between maternal circulating testosterone and left hand 2D:4D [OR = 1.65, 95 % CI 1.1–2.4, p < 0.01].ConclusionsPrevious findings on the association between 2D:4D and social communication difficulties were not confirmed. A novel association between an extreme measure of 2D:4D in males suggests threshold effects and warrants replication.Electronic supplementary materialThe online version of this article (doi:10.1186/s13229-015-0063-7) contains supplementary material, which is available to authorized users.

Testosterone & gift-giving: Mating confidence moderates the association between digit ratios (2D:4D and rel2) and erotic gift-giving

While prenatal testosterone and estrogen have been associated with various masculinized traits such as risk-taking, aggression, athletic ability, and sex drive, little is known regarding the impact of prenatal hormones on male romantic gift-giving. In a sample of 130 Caucasian men, we investigate the association between digit ratios (2D:4D and rel2), a proxy of exposure to prenatal testosterone-to-estrogen ratio, and the likelihood of offering erotic gifts to romantic partners. We hypothesize that men with highly masculinized (low) digit ratios and high mating confidence (i.e., the self-perceived ease with which one gains sexual access to others) will engage in greater erotic gift-giving. We find that masculinized digit ratios are associated with greater erotic gift-giving, but only among men with high mating confidence. Our findings suggest that high prenatal testosterone exposure and high prenatal estrogen exposure are likely to promote a greater desire to offer erotic gifts to a romantic partner, but that only men with high mating confidence have the courage to act on these desires.

Maternal effects, malaria infections and the badge size of the house sparrow

The evolution of sexual signals is not only determined by immediate sexual selection but also by selection arising from the environment and the interaction with developmental effects. In this study we aimed to investigate how the badge size of male house sparrows (Passer domesticus) is correlated to avian malaria infections as well as to prenatal testosterone exposure, measured as the 2D:4D digit ratio. The rationale behind this study is that the immunosuppressive effect of maternal testosterone deposition combined with the fitness cost imposed by parasites may cause important trade-offs to the development of secondary sexual signals. Assuming that vector abundance is a key variable associated with infection risk by avian malaria, we caught adult male sparrows from eight different populations in the Camargue, France, four of which were located in a vector-controlled area, and the other four in an untreated area. For each bird we measured its badge size, digit ratio and took blood to determine its infections status. We used PCR to identify the malaria parasite species and strain that caused the infection. Contrary to our expectation, prevalence of disease did not differ across the vector-treatment regions, with around 80 % of birds being infected in both areas, and those infections were caused largely by a single strain, Plasmodium relictum SGS1. Although infected birds had a badge size not significantly different from uninfected males, there was a condition-dependent association between badge size, infection status and maternal testosterone deposition. This study illustrates that the complexity of temporal and ecological dimensions makes the relationships between disease, testosterone-related traits and secondary sexual signals that have been previously reported less general than thought.

Prenatal Testosterone Exposure Leads to Gonadal Hormone-Dependent Hyperinsulinemia and Gonadal Hormone-Independent Glucose Intolerance in Adult Male Rat Offspring.

Elevated testosterone levels during prenatal life lead to hyperandrogenism and insulin resistance in adult females. This study evaluated whether prenatal testosterone exposure leads to the development of insulin resistance in adult male rats in order to assess the influence of gonadal hormones on glucose homeostasis in these animals. Male offspring of pregnant rats treated with testosterone propionate or its vehicle (control) were examined. A subset of male offspring was orchiectomized at 7 wk of age and reared to adulthood. At 24 wk of age, fat weights, plasma testosterone, glucose homeostasis, pancreas morphology, and gastrocnemius insulin receptor (IR) beta levels were examined. The pups born to testosterone-treated mothers were smaller at birth and remained smaller through adult life, with levels of fat deposition relatively similar to those in controls. Testosterone exposure during prenatal life induced hyperinsulinemia paralleled by an increased HOMA-IR index in a fasting state and glucose intolerance and exaggerated insulin responses following a glucose tolerance test. Prenatal androgen-exposed males had more circulating testosterone during adult life. Gonadectomy prevented hyperandrogenism, reversed hyperinsulinemia, and attenuated glucose-induced insulin responses but did not alter glucose intolerance in these rats. Prenatal androgen-exposed males had decreased pancreatic islet numbers, size, and beta-cell area along with decreased expression of IR in gastrocnemius muscles. Gonadectomy restored pancreatic islet numbers, size, and beta-cell area but did not normalize IRbeta expression. This study shows that prenatal testosterone exposure leads to a defective pancreas and skeletal muscle function in male offspring. Hyperinsulinemia during adult life is gonad-dependent, but glucose intolerance appears to be independent of postnatal testosterone levels.

Maternal testosterone exposure increases anxiety-like behavior and impacts the limbic system in the offspring

During pregnancy, women with polycystic ovary syndrome (PCOS) display high circulating androgen levels that may affect the fetus and increase the risk of mood disorders in offspring. This study investigated whether maternal androgen excess causes anxiety-like behavior in offspring mimicking anxiety disorders in PCOS. The PCOS phenotype was induced in rats following prenatal androgen (PNA) exposure. PNA offspring displayed anxiety-like behavior in the elevated plus maze, which was reversed by flutamide [androgen receptor (AR) blocker] and tamoxifen [selective estrogen receptor (ER) modulator]. Circulating sex steroids did not differ between groups at adult age. The expression of serotonergic and GABAergic genes associated with emotional regulation in the amygdala was consistent with anxiety-like behavior in female, and partly in male PNA offspring. Furthermore, AR expression in amygdala was reduced in female PNA offspring and also in females exposed to testosterone in adult age. To determine whether AR activation in amygdala affects anxiety-like behavior, female rats were given testosterone microinjections into amygdala, which resulted in anxiety-like behavior. Together, these data describe the anxiety-like behavior in PNA offspring and adult females with androgen excess, an impact that seems to occur during fetal life, and is mediated via AR in amygdala, together with changes in ERα, serotonergic, and GABAergic genes in amygdala and hippocampus. The anxiety-like behavior following testosterone microinjections into amygdala demonstrates a key role for AR activation in this brain area. These results suggest that maternal androgen excess may underpin the risk of developing anxiety disorders in daughters and sons of PCOS mothers.

Digit ratio (2D:4D) moderates the relationship between cortisol reactivity and self-reported externalizing behavior in young adolescent males

Although reduced cortisol reactivity to stress and increased circulating testosterone level are hypothesized to be associated with higher levels of externalizing behavior, empirical findings are inconsistent. One factor that may account for the heterogeneity in these relationships is prenatal testosterone exposure. This study examined whether the second-to-fourth digit ratio (2D:4D), a putative marker of prenatal testosterone exposure, moderates the relationships of testosterone and cortisol reactivity with externalizing behavior. Left and right hand 2D:4D and self-reported externalizing behavior were measured in a sample of 353 young adolescents (M age=11.92 years; 178 females; 79.7% African American). Saliva samples were collected before and after a stress task and later assayed for cortisol. Testosterone levels were determined from an AM saliva sample. 2D:4D interacted with cortisol reactivity to predict externalizing behavior in males, but not females. In males, low cortisol reactivity was associated with higher levels of aggression and rule-breaking behavior, but only among subjects with low 2D:4D (i.e., high prenatal testosterone). Findings suggest the importance of a multi-systems approach in which interactions between multiple hormones are taken into account. Furthermore, results demonstrate the importance of considering the organizational influence of prenatal testosterone in order to understand the activational influence of circulating hormones during adolescence.

Prenatal testosterone exposure is related to sexually dimorphic facial morphology in adulthood.

Prenatal testosterone may have a powerful masculinizing effect on postnatal physical characteristics. However, no study has directly tested this hypothesis. Here, we report a 20-year follow-up study that measured testosterone concentrations from the umbilical cord blood of 97 male and 86 female newborns, and procured three-dimensional facial images on these participants in adulthood (range: 21-24 years). Twenty-three Euclidean and geodesic distances were measured from the facial images and an algorithm identified a set of six distances that most effectively distinguished adult males from females. From these distances, a 'gender score' was calculated for each face, indicating the degree of masculinity or femininity. Higher cord testosterone levels were associated with masculinized facial features when males and females were analysed together (n = 183; r = -0.59), as well as when males (n = 86; r = -0.55) and females (n = 97; r = -0.48) were examined separately (p-values < 0.001). The relationships remained significant and substantial after adjusting for potentially confounding variables. Adult circulating testosterone concentrations were available for males but showed no statistically significant relationship with gendered facial morphology (n = 85, r = 0.01, p = 0.93). This study provides the first direct evidence of a link between prenatal testosterone exposure and human facial structure.

P.6.d.010 The 2D:4D digit ratio as biomarker for substance abuse

Purpose: The second (2D, index finger) to fourth (4D, ring finger) digit ratio is a biomarker for prenatal testosterone and estrogen exposure. It has been hypothesized that the developmental origins of health and behavior are modulated by the presence or absence of prenatal sex hormones. Several studies have shown a significant relationship between prenatal testosterone concentrations in amniotic fluid and adult risk taking behavior [1]. As the 2D:4D digit ratio does not change after the age of 2, it may be useful as screening tool for later life substance abuse [2]. The purpose of the current study was to investigate the 2D:4D digit ratio and its potential relationship with drug use and smoking. Methods: A survey was held among N= 1067 Dutch adults (57.6% men), aged 16-55 years old (mean age 23.8 years old). For both hands, digit lengths of the second (2D, index finger) and fourth (4D, ring finger) finger were measured using digital vernier calipers recording to 0.01 mm. Measurements were made from the mid-point of the finger crease proximal to the palm to the tip of the finger. Demographics, smoking status (yes/no) and daily number of cigarettes smoked were recorded. Past year's drug use was rated as (1) never, (2) seldom (1-2 times), (3) now and then (3-11 times), monthly, weekly, or daily. Non-parametric correlations were computed to examine the relationship of the 2D:4D digit ratio with alcohol, drug use, and smoking. In addition, substance use of subjects with a hawk-type (2D:4D 1) were compared. Results: Overall, the left 2D:4D digit ratio correlated significantly with frequency of drug use (r = -0.095, p = 0.003). The right 2D:4D digit ratio correlated significantly with the number of cigarettes smoked (r = -0.092, p = 0.005) and the frequency of drug use (r = -0.125, p = 0.0001). For men, the left 2D:4D digit ratio correlated significantly with frequency of drug use (r = -0.125, p = 0.003). The right 2D:4D digit ratio in men correlated significantly with the number of cigarettes smoked (r = -0.127, p = 0.003) and the frequency of drug use (r = -0.141, p = 0.001). For women, none of the correlations between substance abuse and digit ratio were significant. Subjects with a right 2D:4D1. They also significantly more often were drug users (p = 0.004, 33.6% of hawks versus 24.3% of doves). Conclusion: Subjects with a 2D:4D1. Although the strength of the associations is modest, subjects with a lower 2D:4D digit ratio tend to smoke more cigarettes and use drugs of abuse more frequently.

Prenatal Polychlorinated Biphenyls Exposure And Reproductive Hormones In Adult Male Offspring: Results From The Child Health And Development Studies

Introduction: Polychlorinated biphenyls (PCBs) are ubiquitous persistent organic pollutants which act as endocrine disruptors. The effect of in utero exposure to PCBs on hormonal concentrations in md-life remains unclear. Except for three studies, previous research investigating the relationship between PCB exposure and male sex hormones has been cross-sectional. Here, we examine whether in utero PCB exposure is associated with concentrations of testosterone and follicular stimulating hormone (FSH) in adult males. Methods: We used data from the Study of the Environment and Reproduction (SER), a follow up of adult male offspring from the Child Health and Development Study. Of those men who participated, 204 (mean age 43.7 years) gave a blood sample for the measurement of total testosterone and FSH. Prenatal PCB exposure to 15 congeners was measured in maternal blood samples in the immediate postpartum period. Multivariable regression was used to determine the association between prenatal PCB exposure and concentrations of testosterone and FSH, controlling for age, race, total lipids and BMI. PCBs were grouped according to their proposed mechanism of action and according to the degree of chlorination; individual congeners were also assessed as separate exposure measures. Hormone and PCB concentrations were positively skewed and transformed using the natural log function. Results: Mean (standard deviation) concentrations of total testosterone and FSH were 386 (183) ng/dL and 5.83 (3.99) mIU/mL, respectively. We did not find any associations between exposure and FSH. In both unadjusted and adjusted analyses, maternal PCB183 was associated with increased total testosterone. For each log unit increase in maternal PCB183, log total testosterone increased by 0.15 ng/dL (95% confidence interval (-0.01, 0.31). Conclusions: These results suggest that prenatal exposure to specific PCB congeners is associated with testosterone levels in adulthood.

Digit ratio and autism spectrum disorders in the Avon Longitudinal Study of Parents and Children: a birth cohort study

ObjectivesTo investigate whether second-to-fourth digit ratio (2D:4D), a measure commonly used as a proxy for fetal testosterone exposure, is associated with autism spectrum disorders (ASDs), as predicted by the extreme...

Testosterone at your fingertips: Digit ratios (2D:4D and rel2) as predictors of courtship-related consumption intended to acquire and retain mates

While hormones have been shown to impact a wide range of behaviors, little is known regarding their influence on consumer behavior. The current research examines the association between digit ratios and courtship-related consumption. Digit ratios (2D:4D and rel2) are indicators of prenatal testosterone exposure and are assessed by measuring finger length. In Study 1, masculinized digit ratios (low digit ratios, high prenatal testosterone) in men were associated with greater courtship-related consumption to acquire mates, and this association was stronger for men with high mating confidence. In women, feminized digit ratios (high digit ratios, low prenatal testosterone) were associated with greater courtship-related consumption to acquire mates. In Study 2, men with masculinized digit ratios engaged in greater courtship-related consumption by offering romantic gifts as a means of retaining mates. In women, feminized digit ratios were associated with greater romantic gift giving. Our findings suggest that high prenatal testosterone in men leads to greater courtship-related consumption, whereas low prenatal testosterone leads to greater courtship-related consumption in women.

Neonatal testosterone exposure induces early development of follicular cysts followed by sympathetic ovarian hyperinnervation.

This study analysed the temporal association between ovarian cyst development induced by neonatal androgenisation and sympathetic innervation. Neonatal rats (postnatal Days 1 to 5) were treated with testosterone or dihydrotestosterone and the effects were evaluated at postnatal Days 20, 40, 90 or 180. Ovulation rate, number of cystic follicles and density of sympathetic fibres were analysed. The effects of surgical denervation or gonadotrophin stimulation were also assessed. Rats exposed to testosterone showed no oestrous cycle activity and did not ovulate, maintaining a polycystic ovarian morphology at all ages studied. Also, a significant increase in ovarian density of noradrenergic fibres was detected at postnatal Days 90 and 180. Sympathectomy was unable to re-establish ovarian activity; however, human chorionic gonadotrophin stimulation was enough to induce ovulation. The impact of dihydrotestosterone on ovarian function was less noticeable, showing the coexistence of corpora lutea and cystic structures without changes in sympathetic innervation. Our findings suggest that a remodelling of ovarian sympathetic innervation occurs as a response to modifications in the pattern of follicular growth induced by testosterone. A role of sympathetic innervation in the maintenance of the polycystic condition is suggested.

Challenging the Inevitability of Prostate Enlargement: Low Levels of Benign Prostatic Hyperplasia Among Tsimane Forager-Horticulturalists.

Often considered an inevitable part of male aging, benign prostatic hyperplasia (BPH) is the most common non-life threatening disease to affect men in Western populations. We examine age-related change in prostate size and BPH risk and related serum biomarkers among the Tsimane Amerindians of the Bolivian Amazon who live a traditional lifestyle of hunting and small-scale horticulture. The Tsimane are a critical case study for understanding the etiology of BPH as they have low levels of obesity and metabolic syndrome, as well as lower levels of testosterone than age matched U.S. males, factors associated with BPH in previous research. Ultrasounds were conducted on 348 men aged 28-89 years (median age 56 years). Testosterone, prostate specific antigen, sex hormone binding globulin, and glycosylated hemoglobin were examined in relationship to prostate size and BPH. Tsimane have less than half of the BPH prevalence experienced by U.S. men, and prostate volumes 62.6% smaller. While Tsimane have low levels of testosterone and subclinical levels of metabolic syndrome compared to U.S. men, Tsimane with high testosterone were more likely to experience BPH, as were those with higher glycosylated hemoglobin, suggesting targets for clinical interventions to reduce BPH. These results have clinical significance for the growing number of men taking testosterone supplementation; even at low levels the additional testosterone exposure could be placing these men at higher risk of BPH. Overall, these data suggest that BPH may not have been an inevitable part of male aging throughout human evolutionary history.