Search

The natural lifespan of the ovary is occasionally interrupted by pathological processes; some are known, but many are unknown. Premature ovarian insufficiency (POI) can be a devastating diagnosis for an adolescent or for someone who has yet to start a family. Common causes of POI include genetic and chromosomal defects, autoimmune damage, and cancer treatments. Knowledge of the pathogenesis of this condition and an awareness of contemporary hormone replacement and fertility options are required to design a multidisciplinary therapeutic approach comprising reproductive medicine, endocrinology, clinical psychology, and assisted fertility expertise.

Objective To study the effects of increasingly prosperous diet content on clinical features of polycystic ovary syndrome (PCOS). Design A cross-sectional cohort study of 711 women with PCOS from a heterogeneous population spanning a wide spectrum of socioeconomic strata. Setting Independent hospital. Patient(s) A total of 711 women with PCOS in whom the diagnosis was based on Rotterdam criteria. Results were compared with a locally recruited reference group. Intervention(s) Clinical assessment of women with PCOS. Main Outcome Measure(s) Clinical characteristics were assessed with particular reference to diet composition. Four diet groups were identified: simple rice with vegetables, vegetarian with mixed carbohydrates, nonvegetarian with mixed carbohydrates, and an urban diet of processed foods. Result(s) Women with PCOS showed the characteristic features of raised LH and androstenedione concentrations and increased ovarian volume and antral follicle count. There was a notable association between an increasingly affluent diet, the presence of hirsutism, raised body mass index, insulin resistance, and higher serum antimullerian hormone concentrations. The positive association between antimullerian hormone and body mass index is an unusual feature possibly explained by the wide spectrum of lifestyles in this cohort. Conclusion(s) Urbanization of women in India is associated with increasingly severe phenotype of PCOS, which is likely to have implications on fertility outcomes.

Study Objective To summarize the self-reported sexual experiences of women with vaginal agenesis before treatment and discuss the clinical implications. Design A retrospective review of pretreatment baseline sexuality data and medical records of women with vaginal agenesis seeking vaginal construction. Setting A specialist multidisciplinary center for women with genital differences associated with diverse sex development. Participants One hundred thirty-seven women with untreated vaginal agenesis associated with Mayer-Rokitansky-Kuster-Hauser Syndrome and complete androgen insensitivity syndrome aged 15 to 41 years (mean age, 20 years). Interventions Gynecological examination and completion of questionnaires. Main Outcome Measures (1) Sexual Experiences Questionnaire; (2) Multidimensional Sexuality Questionnaire; (3) Vaginal Self-Perceptions; and (4) vaginal length. Results A sizable proportion of women reported having had sexually intimate experiences before any medical intervention on the vagina. Vaginal length, which ranged from dimple to 7 cm and averaged 2.7 cm for the cohort, was unrelated to the range of sexual experiences. Most women perceived their vagina as being too small, but less than half believed that a sexual partner would notice this. Two-thirds of the cohort subsequently completed the dilation program, which was not predicted by pretreatment vaginal length or sexual experience. Conclusion Contrary to the assumption that a vagina of certain dimensions is a prerequisite for women to “have sex,” many women with Mayer-Rokitansky-Kuster-Hauser syndrome and complete androgen insensitivity syndrome reported having experienced genital and nongenital sexual activities with no medical interventions. It is recommended that treatment providers affirm women's capacity for sexual intimacy, relationships, and enjoyment before they introduce the topic of vaginal construction as a non-urgent choice.

Adrenal insufficiency is managed by hormone replacement therapy, which is far from optimal; the ability to generate functional steroidogenic cells would offer a unique opportunity for a curative approach restoring the complex feedback regulation of the hypothalamic-pituitary-adrenal axis. Here we generated human induced steroidogenic cells (hiSCs) from fibroblasts, blood- and urine-derived cells through forced expression of Steroidogenic Factor-1 and activation of PKA and LHRH pathways. hiSCs had ultrastructural features resembling steroid-secreting cells, expressed steroidogenic enzymes and secreted steroid hormones in response to stimuli. hiSCs successfully engrafted into the mouse kidney capsule and underwent intra-adrenal differentiation. Importantly, the hypocortisolism of hiSCs derived from patients with adrenal insufficiency due to congenital adrenal hyperplasia was rescued by expressing the wild-type version of the defective disease-causing enzymes. Our study provides an effective tool with many potential applications to study adrenal pathobiology in a personalized manner and opens venues for the development of precision therapies.

Highlights ► Lin28 proteins regulate micro RNAs and are implicated in germ cell development. ► We assessed LIN28A and LIN28B in the early human ovary and testis. ► Expression of LIN28A increases in the developing ovary between 6 and 9 weeks conception. ► Expression of LIN28B was lower and did not change. ► Alterations in LIN28A were not found in women with primary ovarian insufficiency., Lin28 proteins are emerging as important regulators of microRNAs in endocrine systems. Lin28a regulates primordial germ cell development and puberty timing in mice, whereas the related protein LIN28B is associated with age at menarche in genome-wide association studies in humans. Here, we studied expression of LIN28A and LIN28B in early human gonad development. LIN28A increased in the developing ovary between 6 and 9 weeks post conception, but not in the developing testis. Immunohistochemistry demonstrated LIN28A in peripheral germ cells. LIN28B was expressed at lower levels in both tissues and did not increase with time. As disruption of Lin28a affects germ cell development in mice, LIN28A was considered a candidate gene for primary ovarian insufficiency (POI) in humans. However, no significant changes were found in 50 women studied. These findings show LIN28A is strongly expressed in germ cells during early human ovary development, but disruption of LIN28A is not a common cause of POI.

Objective To collect information on clinical concerns relating to adolescent girls with disorders of sex development (DSD) during the process of transition from paediatric-to-adult clinical services. Subjects and methods This was a prospective audit of the clinical indications for referral and on-going clinical needs for all girls aged 12–20 years seen in a specialist DSD clinic over a 6-month period. Clinical needs were classified according to level of urgency using a simple ‘traffic light’ classification: green for low, amber for moderate, and red for high. Results Fifty girls were seen during the study period and all were referred from paediatric services. Patients may have had one or more indication(s) for referral to the adult clinic and these were: urology/gynaecology (70%), endocrinology (42%) and psychology (14%). The most common indication for on-going clinical input was psychology, with 46% of patients requiring monitoring and intervention. Of the 14 patients (28%) classified red suggesting they had an urgent clinical need, psychology was a major factor in all but one patient. Conclusion Clinicians working with adolescents with DSD need to develop a co-ordinated programme for transitional care that recognises the importance of psychological input within the multi-disciplinary team.

46XY women is a label that gathers together a number of different conditions for which the natural history in to adult life is still only partially known. A common feature is the difficulty that many women encounter when approaching clinicians. In this review we assemble medical, surgical and psychological literature pertaining adult 46XY women together with our experience gained from an adult DSD clinic. There is increasing awareness for the need for multidisciplinary team involving endocrinologist, gynaecology, nurse specialist and particularly clinical psychologists. Management of adult women with a 46XY karyotype includes several aspects: revising the diagnosis in those with previously incomplete workup; exploring issues of disclosure of details of the diagnosis. Surgery needs to be discussed when the gonads are still in situ and when partial virilisation of genitalia have occurred. To maintain secondary sexual characteristics, for general well being and for bone health, most women require sex steroid replacement continuously until the approximately age of 50 and it is important that the treatment is tailored on individual basis. Women should have access to advice about fertility options involving egg donation and surrogacy.

Turner syndrome (TS) is a model for X chromosome influences on neurodevelopment because it is most commonly caused by absence of one X chromosome and associated with altered brain structure and function. However, all prior in vivo magnetic resonance imaging studies of the brain in TS have either used manual approaches or voxel-based morphometry (VBM) to measure cortical volume (CV). These methods, unlike surface-based morphometry (SBM), cannot measure the two neurobiologically distinct determinants of CV- cortical thickness (CT) and surface area (SA) - which have differing genetic determinants and may be independently altered. Therefore, in 24 adults with X monosomy and 19 healthy female controls, we used SBM to compare (i) lobar CV, CT and SA; (ii) an index of hemispheric gyrification; (iii) CT throughout the cortical sheet; and (iv) CT correlation between cortical regions. Compared to controls, females with TS had (i) significantly increased CT and decreased SA in parietal and occipital lobes (resulting in no significant difference in lobar CV); (ii) reduced hemispheric gyrification bilaterally; (iii) foci of significantly increased CT involving inferior temporal, lateral occipital, intraparietal sulcus (IPS), cingulate and orbitofrontal cortices; and (iv) significantly reduced CT correlation between the left IPS and cortical regions including supramarginal and lateral occipital gyri. Our findings suggest that females with TS have complex, sometimes "opposing", abnormalities in SA/gyrification (decreased) and CT (increased), which can result in no overall detectable differences in CV. Thus, haploinsufficiency of X chromosome genes, may differentially impact the distinct mechanisms shaping SA (e.g. cortical folding) and CT (e.g. dendritic arborization/pruning). CT disruptions are maximal within and between cortical regions previously implicated in the TS cognitive phenotype.

This study investigated early androgen influence on the development of human motor and visuomotor characteristics. Participants, ages 12 to 45 years, were individuals with congenital adrenal hyperplasia (CAH), a disorder causing increased adrenal androgen production before birth (40 females, 29 males) and their unaffected relatives (29 females, 30 males). We investigated grip strength and visuomotor targeting tasks on which males generally outperform females, and fine motor pegboard tasks on which females generally outperform males. Physical characteristics (height and weight) were measured to explore whether body parameters could explain differences in motor skills. Females with CAH were stronger and showed better targeting than unaffected females and showed reduced fine visuomotor skill on one pegboard measure, with no difference on the other. Males with CAH were weaker than unaffected males in grip strength but did not differ on the targeting or pegboard measures. Correction for body size could not explain the findings for females, but suggests that the reduced strength of males with CAH may relate to their smaller stature. Further, the targeting advantage in females with CAH persisted following adjustment for their greater strength. Results in females support the hypothesis that androgen may masculinize, or promote, certain motor characteristics at which males excel, and contribute to defeminization of certain fine motor characteristics at which females excel. Thus, these data suggest that organizational effects of androgens on behavior during prenatal life may extend to motor characteristics and may contribute to general sex differences in motor-related behaviors; however, alternative explanations based on activational influences of androgen or altered experiential factors cannot be excluded without further study. KEYWORDS: congenital adrenal hyperplasia (CAH), androgen, sex, motor, strength, targeting

Most women with Turner syndrome (TS) require life-long replacement therapy with oestrogen and progesterone, and we therefore have to consider the optimal strategy for this treatment for 35 years of continuous use. The forms of oestrogen replacement therapy use in young women with TS are usually borrowed from estrogen replacement therapy (ERT) preparations designed for use in postmenopausal women. There have been few attempts at finding an age-appropriate dose of oestrogen for use in young women. There are many end organ responses for exogenous oestrogen that might be used to guide treatment strategies in young women including those in bone, uterus, arterial walls and liver. In this era of caution with ERT brought about by the women's health initiative (WHI) trials in older women, many young women with TS have been advised to reduce the dose of oestrogen replacement or to terminate oestrogen early. This advice may run counter to the concern over quality of life which is already reduced in this group of women. This paper we will consider a selection of target organs for oestrogen for which data are available in women with TS with particular reference to the starting age of oestrogen and possible effects of dose reduction in adult life. Lastly, ovarian androgen secretion is also lost in women with gonadal dysgenesis and some consideration will need to be given to testosterone replacement in the future.

Dissection or rupture of the aorta accounts for death in 2–8% of women with Turner Syndrome (TS). Dilatation of the root of the aorta, hypertension and bicuspid aortic valve have been reported as predisposing factors for aortic dissection but the underlying pathogenesis of vascular dilation in TS is unknown. Recent papers have revealed that dilatation of the arterial tree in TS extends beyond the aorta to conduit vessels including the carotid and brachial arteries. The distal extent of this dilation is unknown. This finding of widespread arterial dilation appears to represent an unusual ‘vasculopathy’ in Turner's syndrome. In trying to understand the pathogenesis of this vasculopathy, several aspects of arterial wall integrity lend themselves to scrutiny. There may be a defect of composition or remodelling of connective tissue, an inflammatory process or abnormal smooth muscle contractility thinking particularly of the nitric oxide pathway. Such processes can be exacerbated other features of TS including oestrogen deficiency, hypertension and accelerated atherosclerosis.

Testosterone promotes male-typical neural and behavioral development in non-human mammals. There is growing evidence that testosterone exerts similar influences on human development, although the range of behaviors affected is not completely known. This study examined the hypothesis that autistic traits are increased following prenatal exposure to abnormally high levels of testosterone caused by congenital adrenal hyperplasia (CAH). Sixty individuals with CAH (34 female, 26 male) and 49 unaffected relatives (24 female, 25 male) completed the Autism Spectrum Quotient (AQ). Females with CAH scored significantly higher than unaffected females on total AQ score, largely due to enhanced scores on subscales measuring social skills and imagination. These results suggest that prenatal exposure to high levels of testosterone influences some autistic traits and that hormonal factors may be involved in vulnerability to autism.

Background Women with Turner syndrome (TS; 45,X) lack a normal second X chromosome, and many are prescribed exogenous sex and growth hormones (GH). Hence, they allow us an opportunity to investigate genetic and endocrine influences on brain development. Methods We examined brain anatomy and metabolism in 27 adult monosomic TS women and 21 control subjects with volumetric magnetic resonance imaging and magnetic resonance spectroscopy. Results In TS women, regional gray matter volume was significantly smaller in parieto-occipital cortex and caudate nucleus and larger in cerebellar hemispheres. White matter was reduced in the cerebellar hemispheres, parieto-occipital regions, and splenium of the corpus callosum but was increased in the temporal and orbitofrontal lobes and genui of corpus callosum. Women with TS had a significantly lower parietal lobe concentration of N-acetyl aspartate, and higher hippocampal choline. Also, among women with TS, there were significant differences in regional gray matter volumes and/or neuronal integrity, depending upon parental origin of X chromosome and oxandrolone and GH use. Conclusions X chromosome monosomy, imprinting and neuroendocrine milieu modulate human brain development—perhaps in a regionally specific manner.

Turner's syndrome (TS) is a genetic anomaly that results from complete or partial absence of one X chromosome and is the most commonly occurring chromosomal abnormality in females. While most females with TS present at birth or in early childhood, nearly one quarter present at adult services with primary or secondary amenorrhoea. It is only with the advent of clinics dedicated to adults with TS that we have realised the degree of occult pathology present in this group. Adults with TS are thought to have a reduced life expectancy, mainly due to excess cardiovascular risk, but they may also have multiple comorbidities including hypothyroidism, deafness, osteoporosis and the attendant problems of oestrogen deficiency and infertility. Many of these features may be affected by the timing of treatments in paediatrics - particularly the timing of growth hormone (GH) and oestrogen use. It is the role of adult TS services to audit the outcome of TS and to inform their paediatric colleagues of the long-term effects of childhood treatments. Thus, a multidisciplinary approach to focused adult care is needed, with consideration of how to optimise surveillance strategies in these women.

Objective To investigate sexual function in women with complete androgen insensitivity syndrome (CAIS) and to investigate the prevalence of factors that might contribute to sexual difficulties. Design Cross sectional survey and clinical examination. Setting Tertiary hospital multidisciplinary intersex clinic and an international peer support group for CAIS. Patient(s) Sixty-six adult women with CAIS. Intervention(s) Self-completed survey of sexual function, genital normality perceptions, and compliance and satisfaction with vaginal hypoplasia treatments. Hospital case notes review, and genital examination for prevalence of vaginal and clitoral hypoplasia. Main outcome measure(s) Golombok-Rust Inventory of Sexual Satisfaction (GRISS) scores of study participants were compared against the scores of the test validation population (as control). In physical examination participants, anatomical dimensions were assessed against published normal values for clitoral and vaginal sizes. Result(s) We found that 90% of women with CAIS in this study had sexual difficulties when compared with the general female population, most commonly sexual infrequency and vaginal penetration difficulty; 77% perceived their vagina as small, but on genital examination only 35% had vaginal hypoplasia. Conclusion(s) Androgen deficiency leads to sexual problems. Vaginal hypoplasia and negative psychological adaptation to living with an intersex condition are likely to have contributed to the high rates of sexual problems found in this study. Treatments for vaginal hypoplasia need to be evaluated with outcome studies of long-term sexual function, quality of life, and satisfaction. Clinical services for the management of intersex conditions need to be multidisciplinary and aim to optimize the patient's physical and psychological health.

Objective To test the hypothesis that increased serum levels of vascular endothelial growth factor (VEGF) in women with polycystic ovaries or the polycystic ovary syndrome (PCOS) result from excess release by ovarian granulosa cells. Design Prospective study. Setting Academic research setting. Patient(s) Twenty women undergoing IVF treatment, of whom 10 had normal ovaries and 10 had polycystic ovaries. Intervention(s) Human granulosa lutein cells were isolated from follicular fluid obtained on the day of oocyte retrieval. Release of VEGF was assessed after co-incubation of granulosa lutein cells with gonadotropins and insulin. Serum and follicular fluid concentrations of VEGF were measured. Main outcome measure(s) Release of VEGF from granulosa lutein cells and serum levels of VEGF. Result(s) Incubation with human hCG, and luteinizing hormone increased release of VEGF into the culture medium. Insulin alone did not increase release of VEGF, but addition of insulin increased hCG-stimulated release of VEGF. Serum and follicular fluid VEGF concentrations and the amount VEGF released from granulosa lutein cells obtained from women with polycystic ovaries or PCOS and those who developed the ovarian hyperstimulation syndrome were greater than those from granulosa lutein cells obtained from women with normal ovaries and those who did not develop the ovarian hyperstimulation syndrome. Conclusion(s) The amount of VEGF released by granulosa lutein cells is gonadotropin dependent and is augmented by insulin. The increased circulating concentrations of VEGF in women with PCOS may not only be due to an increased number of actively secreting granulosa lutein cells but also due to increased secretory capacity of each granulosa cell.

Turner's syndrome (TS), caused by an absent or structurally abnormal X chromosome, affects 1 in 2500 live female births. Most medical attention has focused on the attainment of final height in childhood and, when this has been achieved, many women are discharged to primary care. It has become increasingly evident that adults with Turner's syndrome are susceptible to a range of disorders such as osteoporosis, hypothyroidism and diabetes. Because of these, and because of the need for long-term oestrogen replacement, it seems most practical for adult health surveillance in TS to come under the remit of the endocrinologist. It must be accepted, however, that the reduced life expectancy in women with TS is largely accounted for by cardiovascular disease. Also, the commonly observed social isolation in adults with TS can be linked to deafness that is increasingly prevalent in an ageing group. Co-ordination of all these issues requires a dedicated multidisciplinary clinic along the lines of those in place in diabetes.

a Department of Child Psychiatry, Institute of Psychiatry, King's College London, London, UK b Child Psychiatry Branch, National Institutes of Mental Health, Bethesda, USA c Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, UK d Department of Endocrinology, Middlesex Hospital, London, UK e Behavioural Sciences Unit, Institute of Child Health, London, UK f Thomas Jefferson University, Philadelphia, USA g The Mouse Imaging Centre, The Hospital for Sick Children, Toronto Centre for Phenogenomics, Toronto, ON, Canada

Objective: To explore the value of serum vascular endothelial growth factor (VEGF) concentrations during IVF cycles in predicting the risk of ovarian hyperstimulation syndrome (OHSS). Design: Prospective study. Setting: London Women's Clinic. Patient(s): One hundred seven women undergoing IVF. Mild OHSS developed in 10 women, moderate OHSS in 7, and severe OHSS in 3. Intervention(s): Serum VEGF concentrations were measured before treatment, after pituitary desensitization, and on the days of hCG administration, oocyte collection, and ET. Main Outcome Measure(s): Serum VEGF concentrations. Result(s): Serum VEGF concentrations were higher in women in whom OHSS developed. The increase in the VEGF concentration that occurred between the day of hCG administration and the day of oocyte collection (the "VEGF rise") was an important marker of OHSS. The VEGF rise was higher in women in whom OHSS developed. A higher VEGF rise predicted all cases of OHSS and moderate/severe cases of OHSS with a sensitivity of 100% and a specificity of 60%. A likelihood ratio test showed that adding the VEGF rise or the VEGF concentration on the day of oocyte collection to a regression model as a continuous variable to the number of follicles, the E 2 concentration, and the presence of polycystic ovaries significantly contributed to predicting the risk of OHSS. Conclusion(s): The results support the role of VEGF as an important nonsteroidal index of ovarian response. The VEGF rise may have an advantage over the E 2 concentration, the number of follicles, and the number of oocytes, which individually predict only 15%–25% of cases of OHSS.

Objective: To relate changes in serum and follicular fluid vascular endothelial growth factor (VEGF) concentrations to Doppler blood flow velocities within ovarian and uterine blood vessels during IVF cycles and to assess their relation to ovarian hyperstimulation syndrome (OHSS) and polycystic ovaries (PCO)/polycystic ovary syndrome (PCOS). Design: Prospective descriptive study. Setting: The London Women’s Clinic. Patient(s): One hundred seven patients receiving a “long” stimulation protocol of IVF. Intervention(s): Doppler blood flows were recorded in ovarian stromal and uterine arteries; serum VEGF was measured in the early follicular phase, after pituitary desensitization, on the day of hCG administration, on the day of oocyte retrieval, and on the day of ET. Main Outcome Measure(s): Serum and follicular fluid VEGF concentrations and Doppler blood flow measurements. Result(s): Serum VEGF concentrations rose after hCG administration. The rise was higher in women in whom OHSS developed. Women with PCO/PCOS had higher serum VEGF concentrations throughout the IVF cycle irrespective of whether OHSS developed. Follicular fluid VEGF concentrations were higher in women in whom OHSS developed and in women with PCO/PCOS. Doppler blood flow velocities in the ovarian blood vessels were higher in women in whom OHSS developed. Within ovarian and uterine blood vessels, blood flow velocities were higher in the early follicular phase and on the day of hCG administration in women with PCO/PCOS. A positive correlation was observed between the serum VEGF and E2 concentrations on the days of hCG administration and oocyte retrieval and between the serum VEGF concentration and Doppler blood flow velocities throughout the IVF cycle. Conclusion(s): Our results support the role of VEGF as a mediator of OHSS and establish a possible link between VEGF, OHSS, and PCO.

Summary The clinical presentation of PCOS is likely to be the end process of many pathogenic mechanisms, the definition of which is only now beginning to be unravelled. While the application of ultrasonography to the diagnosis of PCOS has undoubtedly added greatly to our understanding of the breadth of the disorder and our appreciation of its heterogeneity, careful distinction has to be made between polycystic ovaries and polycystic ovary syndrome in order to define optimal treatments, particularly in women with menstrual disturbance. In the presence of obesity, no treatment regimen can neglect weight reduction as the main thrust of intervention, no matter whether the goal be to improve hirsutism or infertility.

Objective To characterize women with idiopathic premature ovarian failure (POF) by their ovarian ultrasonographic appearances to establish the prevalence of follicular activity and relationship to autoimmunity, estrogen status, and historical background. Design Retrospective analysis of clinical, endocrine, autoimmune, ultrasonographic, and bone densitometry parameters. Setting Reproductive Endocrinology Clinics of The Middlesex Hospital, London, United Kingdom. Patients Data from 135 women with idiopathic POF were analyzed. A reference group of 18 women with normal ovarian function, studied in their follicular phase, was used for comparison of endocrine and ultrasound data. A reference group of 57 women with normal ovarian function was used for comparison of bone densitometry measurements. Main Outcome Measures Serum E 2 concentrations, autoantibody screen, ultrasonographic measures of ovarian volume, uterine cross-sectional area and endometrial thickness and dual roentgenogram bone mineral densitometry of the lumbar spine. Results The detection of ovaries by ultrasound (in 76%) and follicular activity (in 60% of patients) was associated with higher bone mineral density compared with women in whom ovaries could not be identified. Of 13 patients presenting with primary amenorrhea, ultrasonography identified ovaries in 62% and follicles in 38% whereas 38% had positive autoimmunity. Evidence of autoimmunity was found in 31% of patients overall and these were indistinguishable from the nonautoimmune remainder in every respect. Conclusions Ovarian follicular activity, previously considered to be rare, as in the "resistant ovary syndrome," is found in the majority of women with POF using pelvic ultrasonography. Patients presenting with primary amenorrhea have a similar degree of ovarian function, determined by ultrasound, and autoimmunity as those presenting with secondary amenorrhea. The role of autoimmunity in the pathogenesis of POF is not distinguished from nonautoimmune ovarian damage by the measurements made in this study.

Most of the known effects of aldosterone are mediated by the mineralocorticoid receptor, an intracellular receptor belonging to the steroid/thyroid hormone/retinoic acid receptor superfamily. We determined the genomic structure of the human MR (hMR) and identified 10 exons in the gene, including two exons (1 alpha and 1 beta) that encode different 5'-untranslated sequence. Expression of the two different hMR variants is under the control of two different promoters that contain no obvious TATA element, but multiple GC boxes. Our results indicate that hMR expression is regulated by alternative promoters perhaps in a tissue- or developmental-specific manner.

We report the evaluation of a commercial coated tube kit (Medgenix) to the measurement of testosterone in plasma/serum samples. The accuracy, precision, specificity and recovery of the assay and the affinity of antibody for ligand were established. The range of concentrations of testosterone providing satisfactory analyses was 0.48-48 nmol/l, which is appropriate for general clinical use. Results of analysis of male and female samples obtained from the routine hospital laboratory in endocrinologically-defined groups were also reviewed. In all groups of male subjects and in normal females, the kit provided results in close agreement to those of an extraction method. With samples from women with various reproductive disorders, as well as with some samples obtained from external quality controls, the kit showed a small but significant negative bias relative to the results of the extraction method. There was, however, no evidence of bias with samples from a separate group of volunteer women with the polycystic ovary syndrome. No interference due to SHBG was detected. Clinical sensitivities using the kit were equivalent to those obtained using the extraction RIA. There was no evidence of spuriously high results in samples from females which has been a common problem with direct radioimmunoassay of testosterone.

Objective To investigate the role of 11 β -hydroxylase/11 β -hydroxyandrostenedione (11-OHA) in the ovarian metabolism of androgens in women with polycystic ovaries (PCO) and its associated syndrome (PCOS). Design Prospective observational study examining the plasma and follicular fluid (FF) concentrations of 11-OHA, testosterone (T), androstenedione (A), and cortisol from women with PCOS and normal women in spontaneous and stimulated cycles. Setting The study was carried out in an infertility department and an endocrine research laboratory of a university hospital. Patients Five groups of women were studied. Blood was taken from 53 women with PCOS and 13 normal controls. Follicular fluid and blood was obtained from 51 women with stimulated cycles undergoing in vitro fertilization embryo-transfer (IVF-ET), 27 of whom had PCO and 24 had normal ovaries. Follicular fluid alone was also taken from 13 women with normal ovaries undergoing laparoscopies. Interventions Clear FF was obtained for analysis during oocyte collection. Granulosa cells (GCs) were obtained from seven women with PCO undergoing IVF-ET and were incubated with radiolabeled sustrates. Results Circulating concentrations of T and 11-OHA were higher in women with PCOS compared with women with normal ovaries. In women with PCO receiving exogenous gonadotropin, only 11-OHA concentrations were higher. Concentrations of all steroids measured were higher in FF than plasma, with plasma 11-OHA concentrations 4 to 12 times higher in FF. Significantly lower concentrations of 11-OHA were found in the FF of women with PCO compared with women with normal ovaries. There was no evidence of 11 β -hydroxylation of A by GCs. Conclusions Although the raised plasma concentrations of 11-OHA may reflect hyperandrogenism in PCOS and lower 11-OHA concentrations in FF in women with PCO suggest abnormal androgen metabolism, neither can be regarded as a marker for this syndrome.

To characterize the ovarian response in patients with isolated hypogonadotropic hypogonadism with ultrasound (US) findings of polycystic ovaries (PCO).Twenty-seven treatment cycles in patients with hypogonadotropic hypogonadism and US findings of normal ovaries were compared with 31 cycles in patients with hypogonadotropic hypogonadism and US-diagnosed PCO. Forty-one cycles in the hypogonadotropic hypogonadism and US-diagnosed PCO were compared with 59 cycles of patients with polycystic ovarian syndrome (PCOS) to examine pattern of response after ovulation induction.Specialist Reproductive Endocrine Unit.Twenty hypogonadotropic patients in whom 10 had US findings of PCO and 13 patients with PCOS.Serum estradiol (E2) concentration, number of leading follicles on US, cancellation, and pregnancy rate.Hypogonadotropic patients with US-diagnosed PCO had higher baseline ovarian volume (P less than 0.02) compared with patients with hypogonadotropic hypogonadism with normal ovaries. After ovarian stimulation, a higher mean serum E2 concentration (P less than 0.001), endometrial thickness (P less than 0.001), and increased number of leading follicles (P less than 0.0001) were found in hypogonadotropic patients with US-diagnosed PCO, compared with hypogonadotropic patients with US findings of normal ovaries. Patients with PCOS had a higher serum E2 concentration (P less than 0.008), although they were treated for fewer days (P less than 0.0001) and with fewer ampules of gonadotropin (P less than 0.001) compared with patients with hypogonadotropic hypogonadism with US-diagnosed PCO.We have characterized a group of hypogonadotropic patients with US findings of PCO, in which the ovarian response to ovulation induction was similar to patients with PCOS. The results have practical and theoretical implications for the etiology and treatment of patients with PCO.

Summary The reality of the interaction of GH and its mediator, IGF-I, with gonadotrophins is now established. The results of these studies and others have obvious implications, both physiologically and clinically. Co-treatment with GH augments the gonadal response to gonadotrophins, and it seems to be of particular value in patients who are poor responders to gonadotrophin treatment and who have pituitary hypofunction induced surgically, idiopathically (hypogonadotrophic hypogonadism) or medically (treatment with GnRH analogues). There is conflicting evidence as to whether the observed effect of GH is exerted directly on the ovary or mediated through IGF-I. Treatment with GH causes a distinct increase in serum IGF-I concentrations, which correlate with, but are always higher than, follicular fluid levels, suggesting that GH stimulates hepatic production of IGF-I and that the effect on the ovary is endocrine. Further research will, hopefully, clearly define the precise therapeutic role of GH in the induction of ovulation, the selection of the most appropriate group of patients to be treated, and the minimum dose of GH needed to sensitize the ovary. Further studies are also needed to explore the action of GH and to define the role of IGF-I in the process of follicular development.

Objective To induce spermatogenesis by cotreatment with growth hormone (GH) and gonadotropin therapy in patients with hypogonadotropic hypogonadism who had failed to respond adequately to conventional treatment. Design Cotreatment with GH (4 IU) and human menopausal gonadotropin, 150IU of follicle-stimulating hormone and 150IU of luteinizing hormone (LH), three times a week, and human chorionic gonadotropin, 2,500 IU, two times a week for 24 weeks after unsuccessful treatment for 12 weeks with either pulsatile LH-releasing hormone or gonadotropins. Setting Specialist Reproductive Endocrine Unit. Patients, Participants Seven patients, four of whom had failed to respond adequately to the conventional treatment. Main Outcome Measures Serum testosterone (T), estradiol, and sperm production, testicular and semen volume, and serum insulin-like growth factor-I and inhibin concentrations. Results Of the four patients who received cotreatment with GH, three increased T secretion (>11 nmol/L) within a relatively short period of time, two produced adequate amount of sperm (13 and 12 × 10 6 /mL), and one of them impregnated his wife. One patient did not respond. Conclusion The results offer a new approach to the problem of induction of spermatogenesis in patients who respond poorly to conventional treatment because cotreatment with GH enhanced T secretion and sperm production in a relatively short period of time.

To attempt the monitoring of ovulation induction solely with ultrasound (US).Using serial US measurements to monitor ovulation induction using human menopausal gonadotropin and human chorionic gonadotropin (hCG), in comparison with estradiol (E2) concentrations that became available at the end of each cycle.Specialist Reproductive Endocrine Unit.Twenty hypogonadotropic and 29 ultrasonically diagnosed polycystic ovary patients.Follicular growth, uterine measurements, endometrial thickness, and serum E2 concentrations.Follicular growth, uterine measurements, and endometrial thickness correlated strongly with E2 concentrations (P less than 0.0001). The endometrium on the day of hCG administration was significantly thicker (P less than 0.01) in the conception (n = 27) compared with the nonconception cycles (n = 87), whereas no significant difference were observed in serum E2 concentrations. No pregnancy was observed when hCG had been administered when the endometrial thickness was less than or equal to 7 mm. Midluteal endometrial thickness of greater than or equal to 11 mm was found to be a good prognostic factor for detecting early pregnancy (P less than 0.008).Serial US examinations used alone have proven to be safe and highly efficient. It also has a unique ability to detect pregnancy in the midluteal phase.

Objective The objective of the study was to investigate health, well-being, and sexual function in women with Rokitansky syndrome. Study Design Fifty-eight women with Rokitansky syndrome completed 4 questionnaires assessing health-related quality of life, emotional distress, and sexual function and attended for a vaginal examination. Results Participants reported better overall physical health and poorer overall mental health compared with normative data. Anxiety levels were higher, especially for women who had undergone vaginal treatment. Sexual wellness and function scores were poor. Mean vaginal length was 5.4 cm and was greater in women currently sexually active. Vaginal length had a positive correlation with overall sexual satisfaction but was not related to overall quality of life. Conclusion Rokitansky syndrome has a negative impact on emotional and sexual wellness. Relationships between physical and psychological parameters are complex and require further exploration. There is a need for better treatment studies using prospective methodology to assess the effects of surgical and nonsurgical treatments.