Fertility outcomes in male adults with congenital hypogonadotropic hypogonadism treated during puberty with human chorionic gonadotropin and recombinant follicle stimulating hormone.

AIM: Hormone replacement therapy with testosterone for pubertal induction in boys with congenital hypogonadotropic hypogonadism (CHH) achieves virilization but not spermatogenesis. By contrast, human chorionic gonadotropin (hCG) and recombinant follicle stimulating hormone (rFSH) provides both virilization and spermatogenesis. Fertility outcomes of boys treated with recombinant therapy during adolescence have been infrequently described. We report fertility induction and pregnancy outcomes in CHH patients treated with recombinant gonadotropins during puberty. METHODS: Data of six subjects with CHH (n = 3 Kallmann syndrome & n = 3 Isolated hypogonadotropic hypogonadism) treated with hCG and FSH for pubertal induction were reviewed. Of these, five underwent subsequent fertility induction while one desired fertility at the end of pubertal induction. RESULTS: Partners of all subjects achieved pregnancies using hCG and rFSH, all with full term live births. All infants were clinically normal. CONCLUSION: This study provides early evidence of proof of concept of use of gonadotropin induction of puberty being beneficial in subsequent fertility outcome.

Outcomes of one-stage feminizing genitoplasty in children with congenital adrenal hyperplasia and severe virilization.

PURPOSE: To present our surgical experience and outcomes in congenital adrenal hyperplasia (CAH) patients with severe virilization using a combined technique of total urogenital mobilization (TUM) and a modified pull-through vaginoplasty to perform a safe and effective one-stage feminizing genital reconstruction for these children. METHODS: Fourteen CAH patients with severe virilization, defined by a Prader IV and V rating of the external genitalia, underwent TUM followed by a limited vaginal pull-through procedure from June 2016 to December 2020. Postoperative anatomical and cosmetic outcomes, and urinary continence, were evaluated. RESULTS: Out of the 14 cases in this study, 8 were classified as prader IV and 6 as Prader V. The median age at surgery was 11 months (range 6-36 months), and the mean urethral length was 1.4 cm (range 1.2-1.8 cm). The median follow-up period was 4 years. Our cosmetic outcomes were good in 11 (78.5%), satisfactory in 2, and poor in one case. All patients achieved age-appropriate toilet training without urinary incontinence. CONCLUSION: Adopting our surgical approach of TUM with modified pull-through vaginoplasty has simplified feminizing surgical reconstruction in CAH cases with severe genital atypia and a very high vaginal confluence with short urethral length, yielding adequate introitus with good anatomical and cosmetic appearance and adequate urinary continence outcomes.

Development and prenatal exposure to androgens alter potassium currents in gonadotropin-releasing hormone neurons from female mice.

Pulsatile gonadotropin-releasing hormone (GnRH) release is critical for reproduction. Disruptions to GnRH secretion patterns may contribute to polycystic ovary syndrome (PCOS). Prenatally androgenized (PNA) female mice recapitulate many neuroendocrine abnormalities observed in PCOS patients. PNA and development induce changes in spontaneous GnRH neuron firing rate, response to synaptic input, and the afterhyperpolarization potential of the action potential. We hypothesized potassium currents are altered by PNA treatment and/or development. Whole-cell patch-clamp recordings were made of transient and residual potassium currents of GnRH neurons in brain slices from 3-week-old and adult control and PNA females. At 3 weeks of age, PNA treatment increased transient current density versus controls. Development and PNA altered voltage-dependent activation and inactivation of the transient current. In controls, transient current activation and inactivation were depolarized at 3 weeks of age versus in adulthood. In GnRH neurons from 3-week-old mice, transient current activation and inactivation were more depolarized in control than PNA mice. Development and PNA treatment interacted to shift the time-dependence of inactivation and recovery from inactivation. Notably, in cells from adult PNA females, recovery was prolonged compared to all other groups. Activation of the residual current occurred at more depolarized membrane potentials in 3-week-old than adult controls. PNA depolarized activation of the residual current in adults. These findings demonstrate the properties of GnRH neuron potassium currents change during typical development, potentially contributing to puberty, and further suggest PNA treatment may both alter some typical developmental changes and induce additional modifications, which together may underlie aspects of the PNA phenotype. There was not any clinical trial involved in this work.

Fifteen-Year History of Virilization in a 17th-Century Woman.

The Spanish artist, Jusepe de Ribera, painted a portrait of a virilized woman in 1631. He provided a brief clinical history on stone tablets, which indicates that the woman most likely harbored a benign, androgen-secreting ovarian tumor for 15 years.

Androgen receptor actions on AgRP neurons are not a major cause of reproductive and metabolic impairments in peripubertally androgenized mice.

Excess levels of circulating androgens during prenatal or peripubertal development are an important cause of polycystic ovary syndrome (PCOS), with the brain being a key target. Approximately half of the women diagnosed with PCOS also experience metabolic syndrome; common features including obesity, insulin resistance and hyperinsulinemia. Although a large amount of clinical and preclinical evidence has confirmed this relationship between androgens and the reproductive and metabolic features of PCOS, the mechanisms by which androgens cause this dysregulation are unknown. Neuron-specific androgen receptor knockout alleviates some PCOS-like features in a peripubertal dihydrotestosterone (DHT) mouse model, but the specific neuronal populations mediating these effects are undefined. A candidate population is the agouti-related peptide (AgRP)-expressing neurons, which are important for both reproductive and metabolic function. We used a well-characterised peripubertal androgenized mouse model and Cre-loxP transgenics to investigate whether deleting androgen receptors specifically from AgRP neurons can alleviate the induced reproductive and metabolic dysregulation. Androgen receptors were co-expressed in 66% of AgRP neurons in control mice, but only in <2% of AgRP neurons in knockout mice. The number of AgRP neurons was not altered by the treatments. Only 20% of androgen receptor knockout mice showed rescue of DHT-induced androgen-induced anovulation and acyclicity. Furthermore, androgen receptor knockout did not rescue metabolic dysfunction (body weight, adiposity or glucose and insulin tolerance). While we cannot rule out developmental compensation in our model, these results suggest peripubertal androgen excess does not markedly influence Agrp expression and does not dysregulate reproductive and metabolic function through direct actions of androgens onto AgRP neurons.

Ovarian Leydig Cell Tumor Associated with Recurrent Torsion and Virilization in an Adolescent Patient.

Ovarian tumors are rare in children; however, their incidence increases with age. Of these ovarian tumors, Leydig cell tumors are some of the rarest, accounting for less than 0.1% of all ovarian tumors across all ages. Leydig cell tumors predominantly occur in postmenopausal women and are characterized by nodular proliferation of Leydig cells in the ovarian hilum with intracytoplasmic Reinke crystals. These tumors secrete androgens, which can disrupt ovarian function, clinically presenting with abnormal uterine bleeding and virilization. Although they are generally benign, current recommendations are for treatment with a unilateral salpingo-oophorectomy. In adolescents, hyperandrogenism is most commonly caused by polycystic ovarian syndrome (PCOS); however, the differential for hyperandrogenism is broad. We present a case of a 15-year-old girl with a history of primary amenorrhea who presented with a Leydig cell tumor associated with recurrent ovarian torsion and virilization. This case reviews the challenges with diagnosis, management, and future implications of a rare androgen-secreting tumor in young patients.

Adrenocortical carcinoma - 12-year observation period in a single centre. Case report with literature review.

BACKGROUND: Adrenocortical carcinoma (ACC) accounts for 0.2% of childhood malignancies. The most common symptom in children is rapidly progressive androgenization. Herein, we report a case of a patient with symptoms of hypercortisolaemia and androgenization, who was diagnosed with ACC. CASE PRESENTATION: In a 10-year-old patient with ACC the course of the disease was complicated by 3 recurrences. She was treated with surgery, chemo-, and radiotherapy. Currently, 8 years after the end of treatment, there have been no signs of recurrence. CONCLUSIONS: A patient after ACC treatment requires regular check-ups and long-term observation. Constant supervision enables early diagnosis of disease recurrence, and the use of treatment improves the prognosis.

Androgen Excess and Deficiency: Analytical and Diagnostic Approaches.

BACKGROUND: Androgens are synthesized from cholesterol through sequential conversions by enzymes in the adrenal glands and gonads. Serum levels of androgens change during the different phases of life and regulate important developmental and maturational processes. Androgen excess or deficiency can therefore present at various ages in various ways. CONTENT: The diagnostic approach for atypical genitalia, premature pubarche, delayed pubertal onset or progression, and hirsutism or virilization, including measurement of androgens (testosterone, androstenedione, 17-OHprogesterone, dehydroepiandrosterone, and dihydrotestosterone) is discussed in the current review. Androgens can be measured in serum, saliva, urine, or dried blood spots. Techniques to measure androgens, including immunoassays and LC-MS, have their own advantages and pitfalls. In addition, pre- and postanalytical issues are important when measuring androgens. SUMMARY: During clinical interpretation of androgen measurements, it is important to take preanalytical circumstances, such as time of blood withdrawal, into account. As immunoassays have major drawbacks, especially in samples from women and neonates, concentrations measured using these assays should be interpreted with care. Reference intervals can only be used in relation to the measurement technique and the standardization of the assay. In the near future, new androgens will probably be added to the current repertoire to further improve the diagnosis and follow-up of androgen excess or deficiency.

Hypoxia-associated genetic signature in ovarian steroid cell tumor NOS.

Steroid cell tumors, not otherwise specified (SCT-NOS), are uncommon ovarian neoplasms accompanied by virilization symptoms due to hyperandrogenism, which are malignant in approximately one-third of the cases. Given the rarity of SCT-NOS, their molecular underpinnings have not yet been studied in depth. In this case series, we performed the first comprehensive analysis of the genetic landscape of this rare ovarian tumor. A detailed clinicopathological description of an index case is also provided. Over a 20-year period, a total of eight patients were seen at our institution. Total nucleic acids (RNA and DNA) were extracted from evaluable formalin-fixed, paraffin-embedded tumor specimens (n = 7) and subjected to TruSight Oncology 500 testing and/or exome sequencing. The results identified pathogenic variants in several hypoxia-related genes - including HIF1A, VHL, SDHB, SRC, IDH2, and FOXO4. As the first comprehensive genetic analysis of SCT-NOS, this study shows that dysregulation in the hypoxia signaling pathway is a key molecular feature of this rare tumor. Clinically, long-term follow-up with periodic measurements of androgen levels should be pursued in all cases since recurrences may occur several years after the initial diagnosis.

Defining potential targets of prenatal androgen excess: Expression analysis of androgen receptor on hypothalamic neurons in the fetal female mouse brain.

Polycystic ovary syndrome (PCOS) is a female endocrine disorder that is associated with prenatal exposure to excess androgens. In prenatally androgenized (PNA) mice that model PCOS, GABAergic neural transmission to and innervation of GnRH neurons is increased. Evidence suggests that elevated GABAergic innervation originates in the arcuate nucleus (ARC). We hypothesized that GABA-GnRH circuit abnormalities are a direct consequence of PNA, resulting from DHT binding to androgen receptor (AR) in the prenatal brain. However, whether prenatal ARC neurons express AR at the time of PNA treatment is presently unknown. We used RNAScope in situ hybridization to localize AR mRNA (Ar)-expressing cells in healthy gestational day (GD) 17.5 female mouse brains and to assess coexpression levels in specific neuronal phenotypes. Our study revealed that less than 10% of ARC GABA cells expressed Ar. In contrast, we found that ARC kisspeptin neurons, critical regulators of GnRH neurons, were highly colocalized with Ar. Approximately 75% of ARC Kiss1-expressing cells also expressed Ar at GD17.5, suggesting that ARC kisspeptin neurons are potential targets of PNA. Investigating other neuronal populations in the ARC we found that ~50% of pro-opiomelanocortin (Pomc) cells, 22% of tyrosine hydroxylase (Th) cells, 8% of agouti-related protein (Agrp) cells and 8% of somatostatin (Sst) cells express Ar. Lastly, RNAscope in coronal sections showed Ar expression in the medial preoptic area (mPOA), and the ventral part of the lateral septum (vLS). These Ar-expressing regions were highly GABAergic, and 22% of GABA cells in the mPOA and 25% of GABA cells in the vLS also expressed Ar. Our findings identify specific neuronal phenotypes in the ARC, mPOA, and vLS that are androgen sensitive in late gestation. PNA-induced functional changes in these neurons may be related to the development of impaired central mechanisms associated with PCOS-like features.

The alternate pathway of androgen metabolism and window of sensitivity.

Since the discovery in 1968 that dihydrotestosterone (DHT) is a major mediator of androgen action, a convincing body of evidence has accumulated to indicate that the major pathway of DHT formation is the 5α-reduction of circulating testosterone in androgen target tissues. However, we now know that DHT can also be formed in peripheral tissues by the oxidation of 5α-androstane-3α,17ß-diol (adiol). This pathway is responsible for the formation of the male phenotype. We discuss the serendipitous discovery in the tammar wallaby of an alternate pathway by which adiol is formed in the testes, secreted into plasma and converted in peripheral tissues to DHT. This alternate pathway is responsible for virilisation of the urogenital system in this species and is present in the testes at the onset of male puberty of all mammals studied so far. This is the first clear-cut function for steroid 5α-reductase 1 in males. Unexpectedly, the discovery of this pathway in this Australian marsupial has had a major impact in understanding the pathophysiology of aberrant virilisation in female newborns. Overactivity of the alternate pathway appears to explain virilisation in congenital adrenal hyperplasia CAH, in X-linked 46,XY disorders of sex development. It also appears to be important in polycystic ovarian syndrome (PCOS) since PCOS ovaries have enhanced the expression of genes and proteins of the alternate pathway. It is now clear that normal male development in marsupials, rodents and humans requires the action of both the classic and the alternate (backdoor) pathways.

Evaluation of aggression level in adolescent girls with classical congenital adrenal hyperplasia.

OBJECTIVE: In patients with classical congenital adrenal hyperplasia (CAH), virilization affects the brain and external genitalia due to antenatal androgen exposure. There are few studies on how the effects of androgens on brain virilization are reflected in behavior. However, there is no study focused on the adolescence period. The aim of this study was to evaluate the level of aggression in adolescent girls with classical CAH (due to 21 hydroxylase and 11ß hydroxylase deficiency) and to investigate the disease-related factors that may affect aggression. DESIGN: Twenty female and 20 male patients aged 13-20 years, diagnosed with classical CAH, with 21 hydroxylase deficiency and 11ß hydroxylase deficiency, and 20 healthy girls and 20 boys from the same age group were included. The Buss-Perry Aggression Scale (BPAS), which consists of four subgroups measuring physical aggression, verbal aggression, hostility, and angry behaviors, was used. RESULTS: The ages of the male and female patients with CAH were 16.30 ± 2.65 and 16.60 ± 2.41 years, respectively. Total aggression scale scores were 73.3 ± 14.6 in adolescent girls with CAH, 74.1 ± 11.2 in healthy girls, 71.5 ± 14.8 in boys with CAH, and 75.3 ± 14.5 in healthy boys (p > .05). There was no difference between the subscale scores of patients and healthy adolescents. Aggression scores in adolescents with CAH increased significantly with age. CONCLUSIONS: In this study, we found no difference between the aggression scores of adolescents with classical CAH compared to their healthy peers. The total aggression score and subscale were similar in unaffected female adolescents.

Virilization of a 46,XX Fetus Following Aromatase Inhibitor Treatment of Breast Cancer.

Virilization of the 46,XX infant may be attributed to maternal or fetoplacental origin. Maternal sources may be endogenous, as with an androgen-producing tumor, or drug-related. Iatrogenic virilization by maternal drug exposure is rarely reported, with individual case reports and case series demonstrating the effects of progesterone and other medications affecting the pituitary-ovarian axis.1-3 The class of medications known as aromatase inhibitors are recognized as effective in treating hormone receptor-positive breast cancer by preventing the conversion of androgens into estrogens by aromatase. In fetal development, placental aromatase plays a critical role in preventing virilization of the XX fetus by maternal and fetal androgens during development. In the setting of placental aromatase deficiency, the XX fetus may be virilized. It is conceivable, therefore, that maternal exposure to aromatase inhibitors early in gestation may lead to in utero virilization, though there have been no known reports of this phenomenon to date. We present a case of virilization of a 46,XX infant attributed to pharmacologic aromatase inhibition. The infant's parents provided informed consent for the reporting of this case.

Case Report of Male Pseudohermaphroditism (Androgen Insensitivity Syndrome): Congenital Disorder of Sexual Differentiation.

INTRODUCTION: A broad spectrum of anomalies of sexual differentiation may exist at birth, which can be unreported until adolescence. A 17-year-old patent with female phenotype came with complaints of primary amenorrhea. On imaging (ultrasound and MRI) uterus and bilateral ovaries were absent. Small blind-ending vaginal pouch was noted along with features suggesting bilateral cryptorchidism. No definite male external genitalia/scrotal sac was seen except for subtle rudimentary bulbo-cavernous muscles. Karyotyping confirmed 46 XY consistent with Male Pseudohermaphroditism. MATERIALS: Male pseudohermaphroditism refers to a condition that affects 46, XY individuals with differentiated testes who exhibit varying degrees of feminization. In these cases there is a spectrum of external genitalia; some individuals are completely phenotypically female. Androgen insensitivity syndrome (AIS), also known as the testicular feminization syndrome, results from end-organ resistance to androgens, particularly testosterone. As the appearance of the external genitalia often is not distinctive enough to make a specific diagnosis, this must be accomplished by clinical findings along with a combination of imaging, cytogenetic and biochemical studies. Ultrasound and MRI studies are extremely useful to diagnose such conditions at the earliest as these patients have an increased incidence of malignancy in the undescended testes. The treatment is influenced by genital tissue responsiveness to androgens and reconstructive surgical procedures. There is a need for counselling regarding pubertal development, sexual performance and fertility. RESULT: A 17year old patent came with complaints of primary amenorrhea. On examination patient has normal external female genitalia, with developed breast. On laboratory correlation, it shows high testosterone level: 881 ng/dL and Normal progesterone level: 0.182 ng/mL. On karyotyping, it shows 46XY karyotype. On USG: Uterus is not well appreciated. There is iso-echogenic oval shaped soft tissue seen in bilateral inguinal regions with vascularity within-likely to be gonads. On MRI: Absence of uterus and bilateral ovaries are confirmed with evidence of symmetrical oval-shaped soft tissue lesions identified within bilateral inguinal canals - consistent with bilateral cryptorchidism. Male pseudohermaphroditism refers to a condition that affects 46, XY individuals with differentiated testes who exhibit varying degrees of feminization. CONCLUSION: In cases of male pseudohermaphroditism, there is a spectrum of external genitalia; some individuals are completely phenotypically female, whereas others appear to be normal males with varying spermatogenesis and/or pubertal virilization. As the appearance of the external genitalia often is not distinctive enough to make a specific diagnosis, this must be accomplished by clinical findings along with a combination of cytogenetic, biochemical, and radiologic studies. Sonographic and radiographic studies are often used initially to evaluate such conditions. Male pseudohermaphrodites all possess testes yet exhibit incomplete virilization of the genital ducts and/or external genitalia. The findings depend on the underlying defect. Complete androgen insensitivity (testicular feminization) is an X-linked recessive disorder in which the absence of cytoplasmic testosterone receptors prevents specific gene activation and subsequent differentiation of the external genitalia. In this disorder, the external genitalia are completely feminized, while in the other forms of male pseudohermaphroditism various degrees of virilization occur. The absence of internal female genital tract structures reflects the synthesis of active Mullerian regression factor by the testes, which may be maldescended. Multiplanar MR images will confirm the absence of a uterus and demonstrate intraabdominal or inguinal testes. Integrated imaging in the form of ultrasound, genitography and MRI is important in demonstrating the anatomy, classification, possible effects or congenital malformations in other organs, warning patients of any risk of neoplasia and guiding the clinician to plan other investigations, hormonal replacement or reconstruction surgery if required. References Tanaka YO, Mesaki N, Kurosaki Y, et al. Testicular feminization: role of MRI in diagnosing this rare male pseudohermaphroditism. J Comput Assist Tomogr 1998;22(6):884-888. Nakhal RS, Hall-Craggs M, Freeman A, et al. Evaluation of retained testes in adolescent girls and women with complete androgen insensitivity syndrome. Radiology 2013;268(1):153-160.

Pure androgen-secreting adrenal tumor (PASAT): A rare case report of bilateral PASATs and a systematic review.

Background: Adult pure androgen-secreting adrenal tumors (PASATs) are extremely rare, and their characteristics are largely unknown. Methods: A rare case of adult bilateral PASATs was reported, and a systematic literature review of adult PASATs was conducted to summarize the characteristics of PASATs. Results: In total, 48 studies, including 40 case reports and 8 articles, were identified in this review. Analysis based on data of 42 patients (including current case and 41 patients from 40 case reports) showed that average age was 40.48 ± 15.80 years (range of 18-76). The incidence of adult PASAT peaked at 21-30 years old, while that of malignant PASAT peaked at 41-50 years old. Most PASAT patients were female (40/42, 95.23%), and hirsutism was the most common symptom (37/39, 94.87%). Testosterone (T) was the most commonly elevated androgen (36/42, 85.71%), and 26 of 32 tested patients presented increased dehydroepiandrosterone sulfate (DS) levels. In malignancy cases, disease duration was significantly decreased (1.96 vs. 4.51 years, P=0.025), and tumor diameter was significantly increased (8.9 vs. 4.9 cm, p=0.011). Moreover, the androgen levels, namely, T/upper normal range limit (UNRL) (11.94 vs. 4.943, P=0.770) and DS/UNRL (16.5 vs. 5.28, P=0.625), were higher in patients with malignancy. In total, 5 out of 7 patients showed an increase in DS or T in the human chorionic gonadotropin (HCG) stimulation test. Overall, 41 out of 42 patients (including current case) underwent adrenal surgery, and recurrence, metastasis, or death was reported in 5 out of 11 malignant patients even with adjuvant or rescue mitotane chemotherapy. Conclusion: Adult PASAT, which is predominant in women, is characterized by virilism and menstrual dysfunction, especially hirsutism. Elevated T and DS may contribute to the diagnosis of adult PASAT, and HCG stimulation test might also be of help in diagnosis. Patients with malignant PASAT have a shorter disease duration, larger tumor sizes and relatively higher androgen levels. Surgery is recommended for all local PASATs, and Malignancy of PASAT should be fully considered due to the high risk of malignancy, poor prognosis and limited effective approaches.

Case Report: Anastrozole as a monotherapy for pre-pubertal children with non-classic congenital adrenal hyperplasia.

Most children with non-classic congenital adrenal hyperplasia (NC-CAH) due to 21-hydroxylase deficiency are asymptomatic and do not require cortisol replacement therapy unless they develop symptoms of hyperandrogenemia. The current practice is to treat symptomatic children with hydrocortisone aimed at suppressing excess adrenal androgen production irrespective of the child's level of endogenous cortisol production. Once on hydrocortisone therapy, even children with normal cortisol production require stress dosing. Some children with NC-CAH may present with premature adrenarche, growth acceleration, and advanced bone age, but with no signs of genital virilization and normal endogenous cortisol production. In these cases, an alternative therapy to hydrocortisone treatment that does not impact the hypothalamic-pituitary-adrenal axis, but targets increased estrogen production and its effects on bone maturation, could be considered. Aromatase inhibitors (AIs), which block the aromatization of androgen to estrogen, have been used off-label in men with short stature to delay bone maturation and as an adjunct therapy in children with classic CAH. The use of AI as a monotherapy for children with NC-CAH has never been reported. We present three pre-pubertal female children with a diagnosis of NC-CAH treated with anastrozole monotherapy after presenting with advanced bone age, early adrenarche, no signs of genital virilization, and normal peak cortisol in response to ACTH stimulation testing. Bone age z-scores normalized, and all three reached or exceeded their target heights. Monotherapy with anastrozole can be an effective alternative in slowing down bone maturation and improving height outcomes in children with NC-CAH and normal adrenal cortisol production.

Tendencies Toward Supernormality/Subnormality in Generating Attractive and Unattractive Female and Male Avatars: Gender Differences.

In the present study, we investigated the differences in the experience of attractiveness and unattractiveness of human bodies. A total of 101 participants (55 females) were asked to create the most attractive and the most unattractive female and male figures using a computer animation. They performed this task by adjusting the size of six body parts: shoulders, breasts/chest, waist, hips, buttocks, and legs. Analyses indicated that attractive body parts were distributed normally with the peak shifted to moderately supernormal sizes, while unattractive body parts had mostly U-shaped or skewed distributions with extremes in super-supernormal and/or subnormal sizes. Generally, both male and female attractive bodies had prominent "sporty" look: supernormally wide shoulders and long legs. Gender differences showed that men prefer more supernomal masculine and feminine sizes, while women show an ambivalence toward both groups of traits. Principal components analysis revealed gender differences on the multitrait level: males focus on prominent masculine and feminine traits, while women focus on traits that make both male and female bodies more elongated and slender. Gender differences were in line with specific male and female positions in the partner selection process, while a certain tendency toward masculinization of the female body required the inclusion of social factors, such as the influence of the culture of a sporty and fit look.

Maternal androgen excess significantly impairs sexual behavior in male and female mouse offspring: Perspective for a biological origin of sexual dysfunction in PCOS.

Introduction: Polycystic ovary syndrome (PCOS) is the most common infertility disorder worldwide, typically characterised by high circulating androgen levels, oligo- or anovulation, and polycystic ovarian morphology. Sexual dysfunction, including decreased sexual desire and increased sexual dissatisfaction, is also reported by women with PCOS. The origins of these sexual difficulties remain largely unidentified. To investigate potential biological origins of sexual dysfunction in PCOS patients, we asked whether the well-characterized, prenatally androgenized (PNA) mouse model of PCOS exhibits modified sex behaviours and whether central brain circuits associated with female sex behaviour are differentially regulated. As a male equivalent of PCOS is reported in the brothers of women with PCOS, we also investigated the impact of maternal androgen excess on the sex behaviour of male siblings. Methods: Adult male and female offspring of dams exposed to dihydrotestosterone (PNAM/PNAF) or an oil vehicle (VEH) from gestational days 16 to 18 were tested for a suite of sex-specific behaviours. Results: PNAM showed a reduction in their mounting capabilities, however, most of PNAM where able to reach ejaculation by the end of the test similar to the VEH control males. In contrast, PNAF exhibited a significant impairment in the female-typical sexual behaviour, lordosis. Interestingly, while neuronal activation was largely similar between PNAF and VEH females, impaired lordosis behaviour in PNAF was unexpectedly associated with decreased neuronal activation in the dorsomedial hypothalamic nucleus (DMH). Conclusion: Taken together, these data link prenatal androgen exposure that drives a PCOS-like phenotype with altered sexual behaviours in both sexes.