Higher Testosterone Concentrations Research Articles

Androgens Are Differentially Associated with Ovarian Cancer Subtypes in the Ovarian Cancer Cohort Consortium.

Invasive epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. The etiology of EOC remains elusive; however, experimental and epidemiologic data suggest a role for hormone-related exposures in ovarian carcinogenesis and risk factor differences by histologic phenotypes and developmental pathways. Research on prediagnosis androgen concentrations and EOC risk has yielded inconclusive results, and analyses incorporating EOC subtypes are sparse. We conducted a pooled analysis of 7 nested case-control studies in the Ovarian Cancer Cohort Consortium to investigate the association between pre-diagnosis circulating androgens [testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS)], sex hormone binding globulin (SHBG), and EOC risk by tumor characteristics (i.e., histology, grade, and stage). The final study population included 1,331 EOC cases and 3,017 matched controls. Multivariable conditional logistic regression was used to assess risk associations in pooled individual data. Testosterone was positively associated with EOC risk (all subtypes combined, ORlog2 = 1.12; 95% confidence interval 1.02-1.24); other endogenous androgens and SHBG were not associated with overall risk. Higher concentrations of testosterone and androstenedione associated with an increased risk in endometrioid and mucinous tumors [e.g., testosterone, endometrioid tumors, ORlog2 = 1.40 (1.03-1.91)], but not serous or clear cell. An inverse association was observed between androstenedione and high grade serous tumors [ORlog2 = 0.76 (0.60-0.96)]. Our analyses provide further evidence for a role of hormone-related pathways in EOC risk, with differences in associations between androgens and histologic subtypes of EOC. Cancer Res; 77(14); 3951-60. ©2017 AACR.

Is foetal hyperexposure to androgens a cause of PCOS?

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting reproductive-aged women. The pathophysiology of this syndrome is still not completely understood but recent evidence suggests that the intra-uterine environment may be a key factor in the pathogenesis of PCOS, in particular, hyperexposure of the foetus to androgens. High concentrations of maternal serum testosterone during pregnancy have been shown to influence behaviour during childhood, the prevalence of autism disorders and anti-Mullerian hormone (AMH) concentrations in adolescence. They are also thought to re-programme the female reproductive axis to induce the features of PCOS in later life: oligo/anovulation, polycystic ovaries, hyperandrogenism and insulin resistance (IR). Support for this developmental theory for the aetiology of PCOS is gathering momentum, following results from first animal studies and now human data, which lend credence to many aspects of this hypothesis. In this review the recent available evidence is presented to support the hypothesis that hyperandrogenic changes in the intra-uterine environment could play a major part in the aetiological basis of PCOS. An extensive PubMED and MEDline database search was conducted. Relevant studies were identified using a combination of search terms: 'polycystic ovary syndrome', 'PCOS', 'aetiology', 'anti-Mullerian hormone', 'AMH', 'pathogenesis', 'kisspeptin', 'hyperandrogenism', 'insulin resistance', 'metabolic factors', 'placenta', 'developmental hypothesis', 'genetic and epigenetic origins'. A total of 82 studies were finally included in this review. There is robust evidence that a hyperandrogenic intra-uterine environment 'programmes' the genes concerned with ovarian steroidogenesis, insulin metabolism, gonadotrophin secretion and ovarian follicle development resulting in the development of PCOS in adult life. Once the evidence supporting this hypothesis has been expanded by additional studies, the door would be open to find innovative treatments and preventative measures for this very prevalent condition. Such measures could considerably ease the human and economic burden that PCOS creates.

The role of fructose‑1,6‑bisphosphatase 1 in abnormal development of ovarian follicles caused by high testosterone concentration.

The present study aimed to identify the molecular mechanisms underlying the effects of the fructose-1,6-bisphosphatase 1 (FBP1) signaling pathway within normal follicle development and in hyperandrogenism-induced abnormal follicle growth. To achieve this, murine primary follicles, granulosa cells (GCs) and theca-interstitial cells (TICs) were isolated, cultured in vitro and treated with a high concentration of androgens. A concentration of 1×10−5 mol/l testosterone was considerable to induce hyperandrogenism by MTT assay. All cells were divided into four groups, as follows: Control group, testosterone group, androgen receptor antagonist-flutamide group and flutamide + testosterone group. Flutamide was used in the present study as it blocks the effects of the androgen receptor. The mRNA expression levels of FBP1 were detected using reverse transcription-quantitative polymerase chain reaction. The expression levels and localization of FBP1 were analyzed by western blot analysis and immunofluorescence staining. The experimental results demonstrated that androgen presence stimulated follicle development, whereas excessive testosterone inhibited development. FBP1 was identified as being mainly expressed in follicles; FBP1 protein was significantly expressed in GCs of the 14-day-cultured follicle, as well as in the cytoplasm and nuclei of GCs and TICs in vitro. Testosterone increased FBP1 expression during a specific range of testosterone concentrations. Testosterone increased the expression of FBP1 within GCs. Furthermore, FBP1 and phosphoenolpyruvate carboxykinase 1 (PCK1) mRNA expression was increased in GCs treated with testosterone, whereas forkhead box protein O1 (FOXO1) and peroxisome proliferator-activated receptor γ coactivator-1α mRNA expression was significantly decreased in the testosterone group. In TICs, testosterone and flutamide inhibited the mRNA expression levels of FOXO1 and glucose-6-phosphatase enzyme, and promoted the expression of PCK1. These results suggested that the FBP1 signaling pathway may serve an important role in normal follicle growth and hyperandrogenism-induced abnormal development, which may be associated with abnormal glucose metabolism induced by high concentrations of testosterone.

Testosterone, territorial response, and song in seasonally breeding tropical and temperate stonechats

BackgroundTestosterone facilitates physiological, morphological, and behavioral changes required for breeding in male vertebrates. However, testosterone concentrations and the link between its seasonal changes and those in reproductive behaviors vary greatly among species. To better understand the impact of tropical and temperate environments and life history factors on this variation, we have compared testosterone, territorial behavior and song performance across sequential stages of the breeding season in males of 16 closely related taxa of East African tropical and West European temperate stonechats (Saxicola spp), which all breed during a short breeding season, but differ in migratory behavior, seasonal territory-acquisition and pace of life.ResultsWe found that generally, the profiles of testosterone and territorial behavior were similar across latitudes. African stonechats with a slow pace of life had equally high peak testosterone concentrations and responded as aggressively to an intruder as European stonechats with a fast pace of life. However, song performance at the beginning of the breeding season was lower in African than in European stonechats. The differences in song performance were not associated with variation in testosterone levels between tropical and temperate stonechats.ConclusionsThe results suggest a very similar role for testosterone as a mediator of high intensity territorial aggression during the fertile period of females in tropical and temperate stonechats, which all are highly seasonal, locally synchronous breeders. A potential explanation may be high risk of extra-pair copulations which has been associated with synchronous breeding. Interestingly, an association was not consistent for song performance. Our data suggest that song performance can be disassociated from peak testosterone levels depending on its role in breeding behavior. Despite similar testosterone levels, European males, which early in the breeding season acquire territories and mates, showed greater song performance than African stonechats, which maintain year-round territories and pair-bonds. Taken together, our study comparing related taxa of old world songbirds suggests that short breeding seasons may be a major selective force for high peak testosterone levels during breeding regardless of latitude and pace of life, but that particular behaviors, in our case song, can be uncoupled from peak testosterone levels.

Elevated serum interferon γ-inducible protein-10 in women with polycystic ovary syndrome

Background: Interferon γ-induced protein 10 kDa (IP10/CXCL10) is a chemokine related to endocrine disorders; however, the serum concentrations of IP10 in women with polycystic ovary syndrome (PCOS) have not yet been reported. Therefore, we investigated whether IP10 is increased in PCOS patients and its potential clinical value in PCOS patients.Methods: For this research, the serum IP10, glucose, insulin, high sensitivity C-reactive protein (hs-CRP), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and total testosterone (TT) concentrations were measured in 60 women with PCOS and healthy controls.Results: The median IP10 concentration was 45.60 pg/mL [interquartile range (IQR):29.75, 79.69], which was significantly higher than that of the body mass index (BMI)-matched controls (median: 36.46 pg/mL; IQR:28.98, 45.80). In the multivariate linear regression analysis, hs-CRP and the homeostasis model assessment of insulin resistance index (HOMA2-IR) were independent predictors of the IP10 values, while FSH was inversely associated with the IP10.No significant association was observed between the IP10 and BMI, glucose, LH and TT.Conclusions: The serum IP10 concentrations increase in women with PCOS, moreover, IP10 appears to be correlated with the inflammatory and IR statuses of PCOS. IP10 may be a potential biomarker to estimate the disease activity of PCOS.

Gonadotoropin actions on spermatogenesis and hormonal therapies for spermatogenic disorders [Review

Microdissection testicular sperm extraction and intracytoplasmic sperm injection have made it possible for men with non-obstructive azoospermia (NOA) to conceive a child. A majority of men cannot produce sperm because spermatogenesis per se is believed to be "irreversibly" disturbed. For these men, it has been thought that any hormonal therapy will be ineffective. Further understandings of endocrinological regulation of spermatogenesis are needed and LH or FSH receptor knock out (KO) mice have revealed the roles of gonadotropin separately. Spermatogenesis has been shown to shift during evolution from FSH to LH dominance because LH receptor KO causes infertility while FSH receptor KO does not. High concentrations of intratesticular testosterone secreted from Leydig cells, ranging from 100- to 1,000-fold higher than in the systemic circulation, has pivotal roles during spermatogenesis. This is especially important during spermiogenesis, a post-meiotic step for progression from round to elongating spermatids. Sertoli cells are the target of FSH and have numerous androgen receptors, indicating that Sertoli cells are regulated by FSH and the paracrine functions of testosterone. In combination with Leydig cell-derived growth factors, particularly epidermal growth factor-like growth factors, Sertoli cells support spermatogenesis, especially at proximal levels of spermatogenesis (e.g., spermatogonial proliferation). Taken together, the current knowledge from human studies indicating that testosterone optimization by clomiphene, hCG and/or aromatase inhibitors and high dose hCG/FSH treatment can, at least in part, improve spermatogenesis in NOA. Accordingly hormonal therapy may open a therapeutic window for sperm production in selected patients.

Impact of feeding cottonseed coproducts on reproductive system of male sheep during peripubertal period

Cottonseed coproducts contain gossypol which can have specific effects upon the male reproductive system. We evaluated the reproductive development of male lambs close to puberty fed on three cotton coproducts. Twenty-four 5-month old male lambs received four diets: 20 % of dry matter intake of whole cottonseed (WCS), high oil cottonseed meal (CSC), cottonseed meal (CSM), and a control group (CTL) without any cottonseed coproducts. Free gossypol intake was 16.32, 6.98, 5.47 and 0 mg kg−1 BW−1 d−1 for WCS, CSC, CSM and CTL, respectively. Every 15 days, the animals were weighted and serum and semen samples were collected. After 95 days, testis samples were collected for analysis under light and transmission electron microscopes. The CTL group had higher testosterone concentrations than CSC at the end of the trial and lower total sperm defects, higher mass movement and higher scores for seminiferous epithelium than other treatments. The WCS and CSC groups showed higher levels of segmental aplasia lesion in sperm than other diets, which showed that high levels of gossypol led to higher occurrence of this lesion. Cottonseed coproducts had a negative impact on the reproductive system of pubertal lambs regardless of gossypol concentration. Therefore, the use of cottonseed coproducts to feed lambs earmarked for reproduction is not safe.

Application of testosterone to epitestosterone ratio to horse urine – a complementary approach to detect the administrations of testosterone and its pro‐drugs in Thoroughbred geldings

Detection of testosterone and/or its pro-drugs in the gelding is currently regulated by the application of an international threshold for urinary testosterone of 20 ng/mL. The use of steroid ratios may provide a useful supplementary approach to aid in differentiating between the administration of these steroids and unusual physiological conditions that may result in atypically high testosterone concentrations. In the current study, an ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was developed to quantify testosterone (T) and epitestosterone (E). The method was used to analyze 200 post-race urine samples from geldings in order to generate the ratios for the reference population. Following statistical analysis of the data, an upper limit of 5 for T:E ratio in geldings is proposed. Samples collected from 15 geldings with atypical urinary testosterone concentrations (>15 ng/mL) but otherwise normal steroid profile, had T:E ratios within those observed for the reference population. The applicability of an upper T:E ratio to detect an administration was demonstrated by the analysis of a selection of incurred samples from testosterone propionate, dehydroepiandrosterone (DHEA), and a mixture of DHEA and pregnenolone (Equi-Bolic®) administrations. These produced testosterone concentrations above the threshold of 20 ng/mL, but also T:E ratios above the proposed limit of 5. In conclusion, consideration of the T:E ratio appears to be a valuable complementary aid to evaluate whether an atypical testosterone concentration could be caused by a natural biological outlier as opposed to the administration of these steroids. Copyright © 2016 John Wiley & Sons, Ltd.

Age related changes in basal concentrations of FSH, LH and testosterone in indigenous and crossbred bovine males

Collectively, the findings of the present study revealed that the concentrations of both FSH and LH were highest at 18 months of age in crossbred males, while in indigenous males, the FSH and LH concentrations were highest at 18 and 24 month of age, respectively. Higher concentrations of testosterone were observed at 18 months of age in crossbred males and at 24 months of age in indigenous males. These findings may explain the endocrinological support for comparatively late sexual maturity in indigenous males.

Postmenopausal cognitive changes and androgen levels in the context of apolipoprotein E polymorphism.

IntroductionThe focus of this study was to assess cognitive functions in relation to androgens and specifically testosterone and dehydroepiandrosterone in postmenopausal women as well as the correlation between cognitive functions and these two androgens according to polymorphism of the apolipoprotein E gene (APOE).Material and methodsA group of 402 women was recruited to the study (minimum 2 years after the last menstruation, follicle-stimulating hormone (FSH) more than 30 U/ml and no dementia signs on Montreal Cognitive Assessment). The computerized battery of the Central Nervous System Vital Signs test was used to diagnose cognitive functions. APOE genotyping was performed by multiplex polymerase chain reaction (PCR). Testosterone (TTE) and dehydroepiandrosterone (DHEA) in the blood serum were assessed for further statistical correlations analysis.ResultsIn the group of postmenopausal women, higher testosterone concentration was associated with lower scores for Neurocognition Index (NCI) (p = 0.028), memory (p = 0.008) and psychomotor speed (p < 0.001). Presence of at least one APOE ε4 allele potentiated testosterone’s negative influence on cognitive functions (p < 0.05). Woman with a high normal level of DHEA scored significantly better in verbal (p = 0.027) and visual memory (p < 0.001) than other participants. APOE polymorphism did not modify the relationship between DHEA concentration and scores for cognitive functions.ConclusionsHormonal balance variations after menopause may influence brain processes concerned with cognition, especially memory and psychomotor speed. The observed effects may be related to androgens’ influence on higher cortical functions in the changed hormonal dynamics of the postmenopausal period.

Relationships between physiological and behavioral responses of goat bucks in mating season

The objective of this study was to determine the sexual parameters in young bucks with different sexual activity and the effect of experience (age) on sexual parameters in bucks. Fifteen young, sexually inexperienced (SI) and five adult, sexually experienced (SE) Saanen × Hair goat crossbred bucks were used in this study. Bucks were individually exposed to three estrus does for 15-min periods during four sexual performance tests, which were carried out every other day to determine some sexual behavior traits such as flehmen response, reaction time, and ejaculation efficiency. Sexually inexperienced young bucks were evaluated based on their sexual activity (active (AC) vs inactive (IA)) and presence of horn. It was found that AC bucks had significantly higher serum testosterone concentrations (31.5 vs 21.5 ng/mL) and weight loss (114.2 vs 51.2 g/day) than IA bucks. In addition, weight loss was significantly correlated with ejaculation efficiency in young bucks. On the other hand, horned bucks tended to have higher ejaculation efficiency with significantly longer reaction time than polled bucks. For experience (age) classes, SE bucks had higher testosterone concentration (76.0 vs 31.5 ng/mL) and weight loss (16.7 vs 8.6%) than SI active young bucks. However, the effect of experience on other sexual performance traits was found to be limited. Overall, these results indicate that testosterone concentration may affect sexual performance of young bucks in the mating season. Age-related sexual experience is not a determining factor for sexual performance in bucks. However, sexual performance data alone may not reflect reproductive outcomes without semen data.

Cortisol and testosterone accumulation in a low pH recirculating aquaculture system for rainbow trout (Oncorhynchus mykiss )

Steroids accumulate in recirculating aquaculture system (RAS), although explanatory factors for such accumulation are still poorly explored. This study investigated the effect of water exchange rate and pH in six replicated RAS on the concentration of the stress hormone cortisol in rainbow trout blood plasma and in the holding water and of the sex steroids testosterone, 11-ketotestosterone (11-KT) and 17,20β-dihydroxypregn-4-en-3-one (17,20β-P) over a 70-day experimental period. Three combinations of water exchange rate and pH were used each treatment, with two replications: (i) high water exchange rate (±1700 L kg−1 feed) and neutral pH (±7.3), (ii) low water exchange rate (±500 L kg−1 feed) and neutral pH (±7.3) and (iii) low water exchange rate (±500 L kg−1 feed) and low pH (±5.8). Plasma cortisol concentrations at day 70 were higher (24.4 ± 9.5 ng mL−1) for fish kept at low pH when compared to fish kept at neutral pH (12.0 ± 0.1 and 8.7 ± 0.2 ng mL−1). Water cortisol and testosterone concentrations at day 35 were higher at low pH than at neutral pH, whereas water 11-KT and 17,20β-P did not differ among treatments. At day 70, there were no significant differences between low and high pH. These results demonstrate that low pH contributes to increased plasma cortisol concentrations and to its accumulation in water, possibly indicating a stress response to low pH. The higher concentration of testosterone but not of the other sex hormones point to unspecified reproductive effects that need further investigation.

Testosterone levels are positively correlated with cloacal bacterial diversity and the relative abundance of Chlamydiae in breeding male rufous‐collared sparrows

Summary Testosterone mediates several key aspects of male reproduction, but maintaining high testosterone levels can reduce long‐term survival. One of the proposed pathways by which testosterone can influence survival is through increased risk of parasite infection. The hormone has the potential to affect the transmission of sexually transmitted infections by promoting behaviours that increase sexual contact rates and/or by decreasing immune function. We hypothesized that males with high concentrations of testosterone would increase their chances of being infected with sexually transmitted bacteria, which would manifest as increased diversity of cloacal bacteria. To test this hypothesis, we measured circulating testosterone concentrations in breeding male rufous‐collared sparrows (Zonotrichia capensis) and collected cloacal swabs to quantify bacterial diversity using 16S rRNA gene amplicon sequencing. There was a positive correlation between testosterone concentrations and the phylogenetic diversity of cloacal bacteria. In addition, individuals with high and medium testosterone concentrations had cloacal bacterial communities that were more similar to each other than to those of low testosterone individuals. Finally, when considering bacterial taxa that are potential avian pathogens, we found that the relative abundance of Chlamydiae, a class of obligate intracellular parasites, was positively correlated with testosterone concentrations. Two non‐exclusive explanations for these results are that testosterone affects behaviours that lead to increased sexual contacts and thus the exposure and acquisition of additional phylogenetically diverse bacteria, and/or that testosterone is altering the immune system or the cloacal environment, thus making it easier for bacteria to colonize. Either way, these data suggest that increased exposure to sexually transmitted pathogens in the form of cloacal bacteria could be a cost of maintaining high testosterone levels. A Lay Summary is available for this article.

No relationship between prenatal androgen exposure and autistic traits: convergent evidence from studies of children with congenital adrenal hyperplasia and of amniotic testosterone concentrations in typically developing children.

There is a marked male preponderance in autism spectrum conditions. The extreme male brain theory and the fetal androgen theory of autism suggest that elevated prenatal testosterone exposure is a key contributor to autistic traits. The current paper reports findings from two separate studies that test this hypothesis. A parent-report questionnaire, the Childhood Autism Spectrum Test (CAST), was employed to measure autistic traits in both studies. The first study examined autistic traits in young children with congenital adrenal hyperplasia (CAH), a condition causing unusually high concentrations of testosterone prenatally in girls. Eighty one children with CAH (43 girls) and 72 unaffected relatives (41 girls), aged 4-11years, were assessed. The second study examined autistic traits in relation to amniotic testosterone in 92 typically developing children (48 girls), aged 3-5years. Findings from neither study supported the association between prenatal androgen (testosterone) exposure and autistic traits. Specifically, young girls with and without CAH did not differ significantly in CAST scores and amniotic testosterone concentrations were not significantly associated with CAST scores in boys, girls, or the whole sample. These studies do not support a relationship between prenatal testosterone exposure and autistic traits. These findings augment prior research suggesting no consistent relationship between early androgen exposure and autistic traits.

Role of hormonal factor in development of primary and secondary tumorous process in the brain

Introduction. Causes of the development onset of primary malignant cerebral neoplasms have not yet been determined. Not excluded is a possibility of unfavorable effect of the environment, genetic abnormalities, changes alterations in the hormonal background as well as metabolism, ionizing radiation: possible is also the role of viral infections and injuries. One of the main most severest complications of malignant tumors remain are metastatic lesions of the central nervous system whose proportion increases as with the patients’ longlivity. Cerebral metastases of malignant tumors are encountered more often than primary neoplasms of the central nervous system. The brain is not only a hormone-dependent organ the effect of sex hormones as early the embryonic state conditions normal development of the body as a whole and controls the sex related differentiation. It is known that neurons and glyocites like gonads and adrenal glands are able to produce steroid hormones. The enzymes responsible for the synthesis of neurosteroids were detected in the brain tissue in the embryonic period of the development. The human brain is not only a hormone-dependent organ effect influence of sex hormones as early as in the embrional state conditiones normal development of the body as a whole and controls sexual gender differentiation. It is known that neurons and glyocytes like gonads and adrenal glands are able to produce steroid hormones. Enzymes responsible for synthesis of neurosteroids were revealed in cerebral tissue both in during the embryonic period of the development and in adult condition. Besides there are have been obtained large amount of data on the presence in the cerebral cells of receptors to steroidal hormones. In various periods of life the influence effect exerted by steroids on nervous cells can change the morphofunctional state of the brain and manifests as altering myelinization, neuronal growth, and differentiation of nerve cells. The present study was aimed at comparing the level of certain some hormones in tissue of glioblastomes, metastases of breast cancer into the brain and meningiomas, as well as the respective peritumoral zones. Materials and methods. Examined were samples of tissue obtained from a total of 56 patients admitted for operative treatment to our Department. Of these, 24 glioblastomas, 19 breast cancer metastases to the brain, 13 meningiomes without peritumoral edema. The histological control was carried out in all cases. The patients’ age varied form 35 to 72 years. During operative interventions we carried out removed neoplasms of the brain followed by biochemical study of the samples of tumor tissue and immediately adjoining to the tumorous foci tissue (perifocal zone). In 10 % of cytozolic fractions of tissue prepared on the potassium-phosphate buffer of pH 7.4 containing 0.15 of Tween-20 and 1 % of bovine serum albumin by means of immunoenzymatic assay (IEA) using standard test systems we determined the level of steroid hormones – cortisole, testosterone, progesterone, estradiole, estriole, prolactine (IEA, HEMA, Russia) estrone (IEA, DBC, Canada) as well as sex-steroid-binding globulin (IEA, Alcor-Bio, Russia) and hormones of adrenohypophysis – adrenocorticotropine (ACTH) and somatotropic hormone (STH). Results. The obtained findings showed that the most hormonally saturated were metastases of breast cancer. In them along with elevated levels of cortisole, prolactine ACTH and STH concentrations whose concentrations increased virtually in any proliferative process we determined growth of saturation of tissues with estrone and free testosterone on the background of decrease level of active metabolite of estrogens – estriole. Besides, disorders of the steroid metabolism also touched the perifocal zone. Presence of glioblastoma turned out characteristic of identity of tumorous tissue and the perifocal zone by the level of cortizole, which is not found observed if tumors of other genesis. In case of glioblastoms and their perifocal zones the ratio of cortizole to ACTH excedded the norm 2.1–2.5-fold. Meningiomas revealed high concentration of cortisole, ACTH, prolactine, STH, testosterone and sex-binding globulin, as well as a low level of progesterone. In the present study meningiomas turned out liders of production of prolactine and STH as well as estriolle with sufficiently low activity. However alterations of the hormonal background of meningiomas are local isolated form the rest tissues of the brain. Probably, increase of the level of prolactine and STH in tumor tissue is a marker of proliferation, but not malignant cell transformation

Fetal-maternal outcomes and complications in pregnant women with polycystic ovary syndrome.

Earlier studies have shown that polycystic ovary syndrome (PCOS) is associated with cardiovascular disease as well as pregnancy complications. We examined whether women with PCOS have an increased risk of complications in pregnancy compared with healthy women, and if there are any correlations between complications and clinical/demographic variables before and/or in early pregnancy. This retrospective cohort study comprised 37 women with PCOS and 126 healthy women whose birth was recorded at Sundsvall County Hospital, Sweden, from 2009 to 2014. Medical records were searched to identify pregnancy complications, maternal outcomes, and neonatal outcomes. Compared with healthy women, the women with PCOS were more likely to have a history of miscarriage (42.9% vs. 19.8% P=0.005) and undergo caesarean section (41.2% vs. 21.4%, P=0.019). They were also at increased risk of developing a complication (odds ratio 2.38, 95% CI: 1.05-5.38) or having multiple concurrent complications (odds ratio 8.27, 95% CI: 1.45-47.3). The rates of premature birth, birth weight and Apgar score at 5 min were similar between the two groups. The preconception serum testosterone concentration was positively correlated with the complication rate and negatively correlated with gestational age. We found that women with PCOS are at greater risk of complications during pregnancy than healthy women, consistent with the results of earlier studies. High testosterone concentrations could be an aggravating factor in the risk of complications. Therefore, women with PCOS may require more careful monitoring during pregnancy than healthy women.

Valproic Acid Metabolism and its Consequences on Sexual Functions.

Valproic acid (VPA) is a broad spectrum antiepileptic drug (AED) that is generally regarded as a first-choice agent for most forms of idiopathic and symptomatic generalised epilepsies. Available data suggest that menstrual disorders and certain endocrine manifestations of reproductive system disorders may be more common in women treated with VPA than in those treated with other AEDs. A PubMed search for MEDLINE was undertaken to look for studies using the terms "VPA metabolism", "VPA and sexual functions in men", "VPA and sexual functions in women" and "VPA metabolism and endocrine disorders" as key words. The period covered was approximately 20 years. In women, VPA medication is associated with hyperandrogenism, polycystic ovary/polycystic ovarian syndrome, menstrual disorders and ovulatory failure. Men on VPA therapy show abnormalities in androgens blood levels, sperm motility and erectile dysfunctions. VPA negatively affects the release of luteinizing hormone, follicle stimulating hormone and prolactin but also the drug interferes in peripheral endocrine hormones. Its broad inhibitory action on cytochrome and glucuronidation systems can lead to high serum concentration of testosterone, androstenedione and dehydroepiandrosterone sulfate. VPA-dependent obesity and hyperinsulinemia can further contribute to an increase in sexual dysfunctions. VPA interferes with the endocrine system at multiples levels causing several reproductive and sexual dysfunctions in women and men with epilepsy, especially when administered in pubertal age. Since VPA is a first line AED both in children and adult with epilepsy and long-term medication with this drug is sometimes necessary, it is very important for physicians to implement strict monitoring of patients taking VPA in order to identify these kinds of side effects at an early stage.

Seasonal changes in reproductive activity, sperm variables and sperm freezability in Blanca Andaluza bucks

Interest in the preservation of endangered breeds such as the Blanca Andaluza goat, has increased and some steps should be therefore taken to ensure it. The study was designed to determine the seasonal reproductive pattern of Blanca Andaluza bucks, and whether this affects the quality of their semen and its freezability over the year. Seven bucks were used and their body weight, testicular weight, plasma testosterone concentration and fresh sperm quality determined every week. The collected sperm was cryopreserved and stored; it was then thawed and the same sperm quality variables measured every fortnight. High plasma testosterone concentrations were recorded during the summer and autumn, and low concentrations were recorded during winter and spring (p&lt;0.001). No differences were seen between seasons in terms of the percentage of bucks ejaculating, the percentage of active bucks, or ejaculate volume. However, the sperm concentration, the total number of sperm per ejaculate, and the values for most fresh sperm variables were lower during the winter period (at least p&lt;0.05). After freezing-thawing, the quality of winter-collected sperm was better, in some respects, than that of summer-collected sperm (at least p&lt;0.05). These results reveal that Blanca Andaluza bucks show seasonal reproductive activity in terms of their plasma testosterone concentration, but no clear change in their sexual behaviour between seasons was observed. The values of fresh sperm variables also vary over the year, reaching their lowest during winter. However, after freezing-thawing, winter-collected sperm is of overall better quality than sperm collected during the summer.

Changes in Plasma Testosterone and Aggressive Behavior in Male Green Iguanas (Iguana iguana) Following Orchidectomy

Eighteen green iguanas (Iguana iguana) were randomly assigned to three groups: control group (sham orchidectomy); group I (orchidectomy before the breeding season); and group II (orchidectomy during the breeding season). Circulating testosterone concentrations were determined using a radioimmunoassay and correlated with aggressive behavior scores. Monthly mean (± SD) testosterone concentrations and aggression scores varied with group and season. The highest testosterone concentrations were present in the control group (mean ± SD: 11.6 ± 2.8) during the breeding season (November through January). Likewise, the highest aggression scores were present in the control group (11.6 ± 9.6) and group II animals (4.7 ± 2.2) during the breeding season (November through January). Elevations in testosterone concentration preceded initial increases in aggressive behavior by approximately 1 month. Orchidectomy significantly decreased plasma testosterone concentrations between groups, with significant differences seen between the control group and group I animals and between the control group and group II animals. During the breeding season, significant differences in aggressive behavior were found between all three groups. The control group was the most aggressive, and group II animals were more aggressive than group I animals. Linear regression analysis showed a significant positive relationship between plasma testosterone concentrations and aggressive behavior in the control group (P = 0.008).

High levels of testosterone inhibit ovarian follicle development by repressing the FSH signaling pathway.

The effect of high concentrations of testosterone on ovarian follicle development was investigated. Primary follicles and granulosa cells were cultured in vitro in media supplemented with a testosterone concentration gradient. The combined effects of testosterone and follicle-stimulating hormone (FSH) on follicular growth and granulosa cell gonadotropin receptor mRNA expression were also investigated. Follicle growth in the presence of high testosterone concentrations was promoted at early stages (days 1-7), but inhibited at later stage (days 7-14) of in vitro culture. Interestingly, testosterone-induced follicle development arrest was rescued by treatment with high concentrations of FSH (400 mIU/mL). In addition, in cultured granulosa cells, high testosterone concentrations induced cell proliferation, and increased the mRNA expression level of FSH receptor (FSHR), and luteinized hormone/choriogonadotropin receptor. It was concluded that high concentrations of testosterone inhibited follicle development, most likely through regulation of the FSH signaling pathway, although independently from FSHR downregulation. These findings are an important step in further understanding the pathogenesis of polycystic ovary syndrome.