High LH Levels Research Articles

84 A Rare Association of Transient Neonatal Diabetes and Trisomy X

Background: Neonatal diabetes mellitus (NDM) has an incidence of 1/400,000–500,000 live births and is characterized by hyperglycemia with onset in the first 6 weeks after delivery. It may be transient, resolving spontaneously in the first four months or may persist for more than a year (30% of cases). Case report: Preterm newborn, born SGA at 33 weeks of gestational age by emergency caesarian section for acute fetal distress. Family history: paternal grandmother and uncles of mother with diabetes type II, mother with gestational diabetes. Genetic prenatal diagnosis: trisomy X. Apgar at 1 min= 1, intubated and admitted to NICU, assisted ventilation for RDS. Clinical features: patent ductus arteriosus, craniofacial dysmorphism (small ears, retrognathia, cleft palate), left valgus foot. Hyperglycemia at 2 h of life treated with continuous insulin infusion until 3 months of age, than replaced with subcutaneous therapy. At present, insulin therapy has been suspended and glycemic control is good. Clinical and laboratory investigations: High levels of LH, FSH, PRL, E2, PG, testosterone, DEA-S, 17-OHPG, ACTH and glucagons; low levels of basal cortisol; normal levels of GH, FT3, FT4, TSH were detected. Persistent low levels of C-Peptide, absence of anti-insulin, anti-islet and anti-GAD antibodies were also found. Abdominal ultrasonography was normal. The DNA analysis for polymorphism of chromosome 6 showed paternal uniparental isodisomy. Discussion: Transient NDM is associated with uniparental isodisomy of chromosome 6 of paternal origin. Persistent NDM seems to be associated with an inactivating mutation of IPF1, which is necessary for the development of the pancreas as well as for glucose responsive stimulation of insulin gene transcription. The discrimination between transient and persistent NDM is important for both prognosis and therapy. In our opinion the association we found between trisomy X and transient NDM is likely casual. This report is the second one in the literature concerning a patient with transient NDM, uniparental isodisomy of chromosome 6 of paternal origin and trisomy X.

Lumbar bone mineral density in very long-term renal transplant recipients: Impact of circulating sex hormones

The influence of circulating sex hormones and gender on the bone mineral density (BMD) in long-term renal transplant recipients needs further investigation. We performed a retrospective analysis of lumbar BMD between 6 years and 20 years after renal transplantation. In 67 patients (47+/-12 years, 38 male) with a minimum interval of 72 months after transplantation, lumbar BMD measurements (dual energy X-ray absorptiometry) were performed (=complete cohort). Thirty-one patients (=longitudinal cohort) underwent at least three serial BMD measurements (mean follow-up 39+/-18 months, start at 86+/-22 months). All patients received prednisolone. In the complete cohort, BMD was significantly reduced in comparison to young healthy (mean T-score -1.33+/-1.40) and age-matched controls (mean Z-score -0.91+/-1.45) at 88+/-31 months (p<0.05). Osteopenia or osteoporosis were present in two-thirds of patients. In the longitudinal cohort, a mean annual lumbar BMD loss of -0.6+/-1.9% was detectable equivalent to a -0.03+/-0.15 reduction of Z-scores per year (regression analysis). Impact of hormonal status: In the complete cohort, postmenopausal status was associated with significantly lower BMD levels compared to men (p=0.0441). Women and men within the lowest tertile of sex hormone levels (LH, FSH, DHEAS, testosterone, progesterone, estradiol) did not exhibit significant differences in terms of lumbar BMD compared to those in the highest tertile. The mean annual bone loss was statistically indistinguishable between men and women. There was no significant correlation of sex hormone levels and BMD in men and premenopausal women. In postmenopausal women, however, low estradiol and high LH levels correlated with the extent of annual BMD loss (p<0.05). Our data confirm significantly reduced lumbar T-scores in the very late period after renal transplantation. The lumbar BMD decreased by -0.6+/-1.9% per year. In postmenopausal long-term renal transplant recipients, low estradiol levels were associated with accelerated bone loss.

Effect of midfollicular luteinizing hormone levels on ovarian response and pregnancy outcome in patients undergoing in vitro fertilization in a short-term protocol

In a retrospective study, levels of LH in the midfollicular phase had a significant impact on ovarian response and pregnancy outcome. High LH levels were associated with reduced implantation and clinical pregnancy rates.

No evidence of mutations in the P450 aromatase gene in patients with polycystic ovary syndrome

Etiology and inheritance pattern in polycystic ovary syndrome (PCOS) remain uncertain. Granulosa cells from follicles of women with PCOS have little, if any, aromatase (encoded by the CYP19 gene) activity; follicles contain low levels of estradiol, P450arom mRNA and aromatase stimulating bioactivity. Mice with targeted disruption of the CYP19 gene present cystic follicles. It has been proposed that chronic exposure to high levels of LH, because of aromatase deficiency, determines the development of ovarian cysts. Herein, we investigated if mutations in the CYP19 gene and/or its ovary promoter are causal in patients with PCOS. Twenty-five patients with PCOS and 50 control women were studied. PCR analysis of genomic DNA and complete sequence of all exons of the aromatase gene and its ovary promoter were performed. No heterozygous or homozygous mutant alleles were present in any of the patients studied. In the population studied, mutations of the P450arom gene or its promoter are not the cause of PCOS. However, these findings do not preclude the possible importance of an aromatase disorder in PCOS etiology. Variations in aromatase complex function could play a role in PCOS etiology, but the determinants of such variations might be located in other genes.

Hipoplasia das células de Leydig

The Leydig cell hypoplasia is a rare and well defined form of male pseudohermaphroditism with autosomal recessive inheritance pattern. An inadequate fetal testicular Leydig cell differentiation and, consequently a low androgenic production during intra uterine and post natal periods, result in absence or incomplete virilization in patients with 46,XY karyotype. These patients exhibit a wide clinical spectrum, ranging from complete female external genitalia to male external genital with micropenis, low serum testosterone levels associated with high LH levels. Inactivating mutations of the LH/hCG receptor gene have been identified in affected families in the last decade. However, the low frequency of inactivating mutations in this gene, and the lack of segregation of intragenic polymorphisms among affected members from families with typical phenotype of Leydig cell hypoplasia, suggest the genetic heterogeneity of this condition.

Clinical and hormonal features of selective follicle-stimulating hormone (FSH) deficiency due to FSH beta-subunit gene mutations in both sexes

To report the clinical, hormonal, and molecular features of a female adolescent with selective FSH deficiency. In addition, a complete review of previous cases is provided, focusing on hormonal aspects. Clinical study. University hospital. A 16-year-old girl with primary amenorrhea and poor breast development due to isolated FSH deficiency. Blood drawing before and after GnRH stimulation and pelvic ultrasound examination. Gonadotropin and E(2) measurements and sequencing of the FSH beta-subunit gene. The patient was referred for primary amenorrhea and partial breast development (Tanner III). Her basal and GnRH-stimulated LH levels were elevated (31 IU/L and 98 IU/L, respectively), whereas her FSH levels were undetectable (<1 IU/L) in both conditions. Estradiol levels were low (<13 pg/mL). Automatic sequencing showed a nucleotide substitution of C for A in exon 3, resulting in a homozygous nonsense mutation in amino acid position 76 (Tyr76X) of the FSH beta-subunit. The Tyr76X mutation of the FSH beta-subunit was associated with a partial phenotype of FSH deficiency. To date, only four loss-of-function mutations of the FSH beta-subunit have been described in eight patients with undetectable serum FSH and high serum LH levels. Therefore, this unusual hormonal profile strongly suggests a defect in the FSH beta-subunit in both sexes.

Ovarian steroids modulate neuroendocrine dysfunction in polycystic ovary syndrome

Neuroendocrine dysfunction in polycystic ovary syndrome (PCOS) was addressed by studying the steroid hormone changes in women with PCOS with either high or normal LH levels leading to inferences regarding the primacy of elevated LH in the pathophysiology of PCOS. A cross-sectional study was designed in an academic clinical facility involving 234 women with PCOS. Patients were divided into two groups based on an LH/FSH ratio < or >1 and hormonal and metabolic studies were performed in both groups. Factors were determined by binomial logistic regression that predicted group membership of these women. Higher follicular phase estradiol (E2) and androstenedione (A4) levels as well as greater insulin sensitivity were the only factors that predicted the presence of neuroendocrine dysfunction with elevated A4 being necessary for neuroendocrine dysfunction. It was concluded that uncoupling of hypothalamic E2 inhibition by elevated ovarian A4 associated with E2 related sensitization of pituitary LH leads to neuroendocrine dysfunction in PCOS.

Seasonal Profiles of Brain and Pituitary Gonadotropin-Releasing Hormone and Plasma Luteinizing Hormone in Relation to Sex Change of Protandrous Black Porgy, Acanthopagrus schlegeli1

Three molecular variants of GnRH in the brain (sbGnRH, sGnRH, and cGnRH-II) and two forms in the pituitary (sbGnRH and sGnRH) were detected in protandrous black porgy, Acanthopagrus schlegeli using chromatographic and immunological methods. In juvenile fish, brain sbGnRH, sGnRH, and cGnRH-II levels increased in May and reached their highest levels in July and August (the nonspawning season) and in January through March (the spawning season). In fish aged 1 yr and older, high levels of brain sbGnRH and sGnRH were detected in September, November, and February-March, but the levels of brain cGnRH-II remained constant. A gradual increase in pituitary sbGnRH was detected in juvenile fish from July to March. In fish aged 1+ yr, pituitary sbGnRH levels were high in September and March-May, but low in January-February. A close correlation between pituitary sbGnRH and plasma LH levels was found in juvenile fish and in those aged 1+ yr. In fish aged 2+ yr, significantly lower levels of plasma LH was detected during the nonspawning period in fish that changed sex compared with the fish that remained as males. Higher plasma LH levels were detected in the sex-changing fish from artificially sex-reversed female to male. FSH receptor and LH receptor transcripts were higher in bisexual testicular tissue than in ovarian tissue in 2+-yr-old fish. Direct effects of hCG on sex change were studied and the results show that exogenous hCG did not stimulate gonadal aromatase activity in 2+-yr-old fish. Therefore, it is suggested that high and basal levels of plasma LH during the nonspawning season correlate with the development of male and female gonad, respectively, in black porgy. This important role of the neuroendocrine system in sex change (for male direction) is proposed in hermaphroditic fish.

Effects of thymulin and GnRH on the release of gonadotropins by in vitro pituitary cells obtained from rats in each day of estrous cycle

The effects of thymulin and GnRH on FSH and LH release were studied in suspension cultures of anterior pituitary cells from female adult rats sacrificed on each day of the estrous cycle. The spontaneous release of gonadotropins by pituitaries, as well as their response to GnRH or thymulin addition, fluctuated during the estrous cycle. Adding thymulin to pituitary cells from rats in diestrus 1 increased the concentration of FSH; while in cells from rats in estrus, FSH level decreased. Thymulin had a stimulatory effect on the basal concentration of LH during most days of the estrous cycle. Adding GnRH increased FSH release in cells from rats in diestrus 1, diestrus 2, or proestrus, and resulted in higher LH levels in cells obtained from rats in all days of the estrous cycle. Compared to the GnRH treatment, the simultaneous addition of thymulin and GnRH to cells from rats in diestrus 1, diestrus 2, or proestrus resulted in lower FSH concentrations. Similar results were observed in the LH release by cells from rats in diestrus 1, while in cells from rats in proestrus or estrus, LH concentrations increased. A directly proportional relation between progesterone serum levels and the effects of thymulin on FSH release was observed. These data suggest that thymulin plays a dual role in the release of gonadotropins, and that its effects depend on the hormonal status of the donor's pituitary.

The Role of Inhibin and Activin in Adrenal Tumorigenesis

Inhibin and activin are members of the TGFβ family of ligands, which were initially cloned as opposing hormones regulating pituitary FSH secretion. Since their initial characterization, both inhibin and activin have also been shown to play a critical role as paracrine and autocrine factors in regulating growth and differentiation of a variety of tissues including the adrenal cortex. While inhibin is mainly expressed and secreted by the adrenal cortex and gonads, activin expression is more widespread where it exerts its effects by modulating cellular differentiation, survival, proliferation, and apoptosis. Much of our knowledge about the physiological function of inhibin originates from studies on mice with targeted deletion of the inhibin alpha subunit gene (INH-/-). INH-/- mice develop gonadal tumors and – when gonadectomized (GDX) – X-zone-derived adrenal tumors. These findings suggest that inhibin functions as a tumor suppressor in both the gonads and adrenals in vivo. The mechanisms leading to adrenal tumorigenesis after GDX in INH-/- have been proposed to involve the lack of a gonadal factor and/or compensatory increase of gonadotropins. Crossing experiments of INH-/- mice with a transgenic mouse strain that has chronically elevated LH levels (LH-CTP) reveals a growth promoting effect of high levels of LH upon gonadal tumorigenesis. In contrast, ovarian tumor presence in compound INH-/-:LH-CTP is associated with smaller adrenals with a regressed x-zone, suggesting that elevated LH levels are not sufficient to induce adrenal tumor formation. However, following gonadectomy, INH-/-:LH-CTP mice develop large adrenal tumors, indicating a direct growth-promoting effect of LH on the adrenal cortex in the absence of ovarian tumors. Activin, which is secreted in high quantities from ovarian tumors in compound INH-/-:LH-CTP mice, has been reported to induce apoptosis in human fetal adrenal cells. Expression of Smad2, which has a pivotal role within the activin signaling cascade, is restricted to cells of the adrenal x-zone suggesting that the main site of activin action in the adrenal could be the x-zone. Accordingly, activin induces apoptosis specifically in the adrenal x-zone when injected in intact adrenals. Taken together, these findings support the concept that activin prevents adrenal tumor growth by inducing x-zone regression in contrast to LH, which exerts a growth promoting effect on adrenocortical tumors in INH-/- mice. Further clinical studies are needed to evaluate the role of the activin/inhibin/Smad system in patients with benign and malignant adrenal tumors.

Endometrial receptivity following early start and single dose of GnRH antagonists in patients with PCOS

To compare the effects of 2 GnRH antagonist protocols (Fixed and single dose) on endometrial receptivity using immunohistochemical criteria of epithelial integrin expression in PCOS patients. Prospective randomized clinical study. Infertile PCOS women who were randomized to fixed (0.25 started on day 6, n:4), and single dose(3mg started when the leading follicle>15 mm, n:5) regimens of GnRH antagonist(cetrorelix 0.25 and 3). All received rFSH(follitropin alpha) 150 IU starting on menstrual day 2. Endometrial biopsy was obtained 3 days after oocyte retrieval. Immunohistochemical staining intensity and distribution (HSCORE) of αvβ3 subunit integrins and traditional histologic endometrial dating were compared. There were no significant differences among the groups with respect to baseline characteristics. Although both protocols produced similar folliculogenesis, the changes in endometrial receptivity as determined by integrin positivity and HSCORE were better in the fixed protocol (integrin positivity 4 vs 2 respectively). The androgen levels and progesterone on day of HCG and later were greater in the single dose protocol. Eight of the 9 endometrial samples were in phase histologically, distributed similarly through the 2 patient groups(all advanced 1–2 days). Integrin αvβ3 expression was not predicted by in-phase histology, with integrin staining low in all three groups). Just as presence of integrin was not associated with in-phase histology, neither was intensity of integrin staining as measured by the mean HSCORE. Although both protocols were similar in follicular recruitment in PCOS, endometrial receptivity and luteal hormonal mileu were not similarly enhanced. High LH levels at initiation of the cycle and increased androgens may be better suppressed earlier by fixed protocol than single dose. The above changes together with increased exposure to FSH in the single dose group may be the cause of suboptimal endometrium and implantation in PCOS. Although data with antogonist and PCO are limited further trials may outline the exact interaction between the hormonal characteristics of PCO and use of antagonists. Thus may explain the observation of reduced implantation or high miscarriage rates in PCOS patients who conceive with conventional COH with or without GnRH-a.

LH surge is associated with higher LH levels and more physiologic estradiol levels in aromatase inhibitor ovarian stimulation cycles

LH surge is associated with higher LH levels and more physiologic estradiol levels in aromatase inhibitor ovarian stimulation cycles

Ovulation induction using laparoscopic ovarian drilling in women with polycystic ovarian syndrome: predictors of success.

Although laparoscopic ovarian drilling (LOD) has been widely used to induce ovulation in women with polycystic ovarian syndrome (PCOS), predicting the clinical response to this treatment remains to be elucidated further. This study was carried out to identify factors that may help to predict the outcome of LOD. This retrospective study included 200 patients with anovulatory infertility due to PCOS who underwent LOD between 1990 and 2002. The influence of the various patients' pre-operative characteristics on the ovulation and pregnancy rates after LOD was evaluated. In addition, women were divided into two or three categories according to the severity of each of the various clinical and biochemical parameters of PCOS. The success rates were compared between the categories of each factor using contingency table analyses. Multiple logistic regression analysis was used to identify independent predictors of success of LOD. Women with body mass index (BMI) > or = 35 kg/m2, serum testosterone concentration > or = 4.5 nmol/l, free androgen index (FAI) > or = 15 and/or with duration of infertility > 3 years seem to be poor responders to LOD. In LOD responders, serum LH levels > 10 IU/l appeared to be associated with higher pregnancy rates. Marked obesity, marked hyperandrogenism and/or long duration of infertility in women with PCOS seem to predict resistance to LOD. High LH levels in LOD responders appear to predict higher probability of pregnancy.

Function of androgen receptor in gene regulations

Most of the androgen actions are considered to be mediated by the androgen receptor (AR) of the target genes. The AR is composed of a fairly large molecule because of the long A/B domains of its N-terminal. However, the independent roles of the AR as well as those of the estrogen receptors largely remained unknown mainly due to the lack of the AR knockout (ARKO) mice line. We have succeeded in generating the ARKO mouse by means of a conditional targeting using the Cre/loxP system. The ARKO males grew healthily although they showed a typical feature of the testicular feminization mutation (Tfm) and the hormonal assay revealed significantly lower serum androgen and higher LH levels in comparison with those of the wild type (WT) males. The serum estrogen levels were, however, comparable between both the ARKO and the WT. Another hallmark of the ARKO males was a state of high bone turnover osteopenia, in which the acceleration in the bone resorption clearly exceeded the bone formation. Male-typical behaviors were disrupted in male ARKO mice. Aiming at a quick differentiation of an androgen-dependent polyQ disease such as Kennedy’s disease, the authors also developed the Drosophila fly-eye model in which the wild type and the polyQ-expanded human AR (hAR) was induced in the eyes of Drosophila. When androgen was administered to the flies induced with the polyQ-expanded hAR, their optical nerves were devastated.

Relationship between serum gonadotropins and spermatogenic suppression in men undergoing steroidal contraceptive treatment.

This study aimed to establish whether the degree of suppression of serum FSH and LH was related to sperm concentration in three testosterone (T) plus progestin contraceptive regimens. We measured serum FSH and LH using a modified, highly sensitive immunofluorometric assay in samples obtained from three published studies using T enanthate (TE; 100 and 200 mg weekly) plus daily oral doses of cyproterone acetate (CPA; 5-100 mg), levonogestrel (LNG; 150-500 micro g), or desogestrel (DSG; 150-300 micro g). Overall, men with sperm concentrations below 0.1 million/ml had significantly lower gonadotropin levels (serum FSH, approximately 0.12 IU/liter; serum LH, approximately 0.05 IU/liter) than oligospermic men (sperm concentrations, 0.1-5 million/ml; serum FSH, 0.23-0.5 IU/liter; serum LH, 0.05-0.56 IU/liter), but the relationship was weak, indicating the possible existence of other determinants. Multivariate logistic regression was used to identify the influence of candidate predictors of spermatogenic effects of the T plus progestin regimens. In the LNG and DSG studies, the marked suppression of serum LH to less than 5% of baseline values (<0.15 IU/liter) was a consistent and highly significant predictor of sperm concentration (reduced to 2-7% that seen at higher LH levels) and the likelihood of its suppression below 1 million/ml (a proposed threshold for contraceptive efficacy). Serum FSH was not a significant independent predictor. The use of DSG and CPA (but not LNG) was a significant independent predictor of sperm suppression, and regimens that contained 200 mg TE weekly caused less spermatogenic suppression than 100 mg TE weekly. These findings suggest that T-progestin contraceptive regimens suppress sperm concentration by gonadotropin-dependent and -independent mechanisms. The suppression of serum LH is a major predictor of the suppression of sperm concentration suppression in the LNG and DSG treatment studies. On the other hand, the greater spermatogenic suppression in regimens containing DSG or CPA suggests that these progestins have additional actions to suppress spermatogenesis via a gonadotropin-independent mechanism(s)

Aspectos neuroendócrinos da síndrome metabólica

A síndrome metabólica (SM) é caracterizada por alterações no metabolismo glicídico, obesidade, hipertensão e dislipidemia. Estas alterações metabólicas interrelacionam-se com diversos eixos endócrinos controlados pelo hipotálamo e pela hipófise. A obesidade central parece relacionar-se a uma hiperativação do eixo hipotálamo-hipófise-adrenal, como também do sistema nervoso simpático, que poderia levar a um quadro de hipercortisolismo sub-clínico e hipertensão arterial. A SM é também um estado de hipo-somatotropismo relativo relacionado à gordura visceral. Além disso, níveis elevados de ácidos graxos livres e a hiperinsulinemia, secundários à resistência insulínica, estão relacionadas a um bloqueio do eixo somatotrófico. Em homens, a SM relaciona-se a um hipogonadismo tanto por diminuição de gonadotrofinas como por inibição direta da produção de testosterona. Já nas mulheres, existe um excesso de produção de androgênios, principalmente relacionado à hiperinsulinemia, aumento da atividade da aromatase e da liberação de LH. Desta forma, a SM é um estado relacionado a importantes modificações nos mecanismos de feedback responsáveis pelo correto funcionamento dos eixos neuroendócrinos.

Diagnostic role of inhibin B in resistant ovary syndrome associated with secondary amenorrhea

Objective To report two rare cases of gonadotropin-resistant ovary syndrome associated with secondary amenorrhea and normal levels of inhibin B. Design Case report. Setting Two university teaching hospitals. Patient(s) Two women presenting with secondary amenorrhea and infertility. The control group for the inhibin B levels consisted of 30 cycling women of reproductive age. Intervention(s) Medical history, physical examination, laboratory data, histologic findings, and IVF results. Main outcome measure(s) Diagnosis and treatment of resistant ovary syndrome. Result(s) Case 1 was a 25-year-old woman with secondary amenorrhea and primary infertility. She had high serum levels of FSH and LH, low E 2 levels, and normal inhibin B levels (62 pg/mL). Karyotype was 46,XX, and ovarian biopsy showed primordial follicles with oocytes. Administration of GnRH analogue with hMG for 15 days did not affect E 2 levels. She had a successful pregnancy with IVF using donor oocytes. Case 2 was a 24-year-old woman with secondary amenorrhea. She had elevated serum levels of FSH and LH, low E 2 levels, and normal inhibin B levels (57 pg/mL). Karyotype was 46,XX and ovarian biopsy showed primordial follicles. Administration of GnRH analogue with hMG for 12 days did not affect E 2 levels. Both women were given estrogen–progestin replacement therapy. Conclusion(s) Inhibin B has a diagnostic role in women with gonadotropin-resistant ovary syndrome associated with secondary amenorrhea. A review of the literature confirms the uniqueness of the diagnostic role of inhibin B in these cases.

Bone Loss at the Femoral Neck in Premenopausal White Women: Effects of Weight Change and Sex-Hormone Levels

This study measured bone mineral content (BMC), bone mineral density (BMD), and bone area at the spine and hip to learn whether bone loss takes place premenopausally. Participants were 130 non-Hispanic white women 31 to 50 years of age who were in good general health and had taken no drugs that affect bone metabolism. Measurements were made by dual-energy x-ray absorptiometry at the L2-4 segment of the lumbar spine, in the femoral neck, and in the total hip. The studies were repeated at least twice over 1 to 9 years. Both BMC and bone area increased significantly over time in the spine, as did BMD. If, however, BMC was normalized by bone volume, there was no age-related change in volumetric density. Measurements of the total hip showed no significant change with age. BMD in the femoral neck declined at a rate of about 0.0036 g/cm2 per year. BMC was lost as well, so the drop in BMD was not an artifact of bone expansion. Changes in BMD correlated positively with weight change and estradiol levels and negatively with gonadotropin levels. Somewhat less bone loss was noted in subjects who gained more weight during the study. Higher levels of LH and FSH were documented in women who lost more than 1% of BMD per year. Estrogen levels were highest in women who manifested no bone loss. Declining BMD was more a result of a loss of BMC in women with high FSH levels, but due more to an expansion in bone area in those with relatively low FSH levels. The positive association between body weight change and BMD was not entirely mediated by higher estrogen. Premenopausal women more than 30 years of age in this study lost BMD at the femoral neck at an average annual rate of 0.4%. Bone loss was less in women who gained more weight but greater in those with reduced estrogen levels even in the absence of symptoms. Early bone loss might be preventable if premenopausal women with suboptimal sex hormone levels are detected at an early stage.

Inhibin A and B in adolescents and young adults with Turner's syndrome and no sign of spontaneous puberty.

The aim of this study was to assess levels of inhibin A and B, FSH and LH in Turner's syndrome (TS) without signs of spontaneous ovarian activity. Twenty-four girls with TS (median age, 14.7 years) without signs of spontaneous ovarian function were included in the study. Sixty prepubertal girls (PPG) (10.3 years) that had not yet experienced menarche (all Tanner stage 1), and 34 pubertal girls (PG) (13.8 years) (Tanner stage 3-4), who were regularly menstruating, served as controls. The levels of inhibin A and B, FSH, LH, and pubertal stage were determined. Inhibin A was not detected in females with TS, or in almost all PPG (59 of 60) (P = not significant), and inhibin B in TS females, while most PPG produced inhibin B (53 of 60, P < 0.0005). FSH and LH were elevated in TS, but with overlapping values. In follow-up samples in TS, three of twenty-four females showed detectable levels of inhibin A and/or B. In one of these, 6 serial samples were available. At 20 years this patient had a high level of LH and FSH, which declined, and concurrently inhibin A and inhibin B rose, only later to decrease, when FSH and LH started to rise again. In comparison with PG baseline levels of inhibin A and B were lower in TS, with inhibin A detectable in 23 of 34, and inhibin B detectable in 32 of 34 PG. Levels of FSH and LH were also different, although with overlapping values. The result raises the possibility that functional or partly functional ovaries are present in some females with TS, without apparent menstrual cycling.

Obesity and serum luteinizing hormone level have an independent and opposite effect on the serum inhibin B level in patients with polycystic ovary syndrome

Objective: To elucidate whether the negative effect of obesity on the serum inhibin B level that we previously reported is specific or not to polycystic ovary syndrome (PCOS) and whether it may explain the wide interindividual variability in serum inhibin B levels found in patients with PCOS. Design: Prospective study. Setting: Reproductive endocrinology unit of an academic medical center. Patient(s): One hundred thirty-four consecutive patients with PCOS (mean age, 27.4 ± 4.7 years; mean body mass index [BMI], 28.3 ± 7.6 kg/m 2; BMI > 25, 53%) and in 78 control women (mean age, 30.1 ± 4.1 years; mean BMI, 24.3 ± 4.9; BMI > 25, 34%). Intervention: Blood sampling was performed in the early follicular phase in patients and in control women. Main Outcome Measure(s): BMI and waist circumference (WC), serum levels of inhibin B, LH, FSH, E 2, androstenedione, T, fasting insulin, and leptin were assessed in all subjects. Result(s): No difference was observed in the mean inhibin B level between patients and controls. The BMI and WC correlated negatively with inhibin B in patients with PCOS and in controls, with similar regression slopes, thus indicating that the influence of obesity on inhibin B is not specific to PCOS. In addition, we found a positive relationship between serum LH and inhibin B levels in PCOS. There was no significant interaction between the effects of BMI and LH on the serum inhibin B levels by analysis of variance (ANOVA). The mean serum inhibin B level in patients with PCOS with high serum LH (i.e., >the 90th percentile of LH in controls) was significantly higher than in those patients with normal LH or in controls. The highest mean inhibin B level was noted in nonobese patients with PCOS with high LH levels (121.0 ± 51.2 pg/mL), while nonobese patients with PCOS with normal LH levels and obese patients with normal LH or high LH levels had similar mean levels (94.5 ± 40.0, 84.9 ± 34 and 91.6 ± 51.7 pg/mL, respectively). Conclusion(s): We confirm that obesity has a negative effect on inhibin B serum level, which is not specific to PCOS. Obesity and excess LH, acting oppositely and independently on inhibin B production, may explain the discrepancies between the previous reports studying serum inhibin B level in patients with PCOS. Further work is required to elucidate the mechanisms underlying the antagonistic effects of LH and obesity on inhibin B production in patients with PCOS.