Higher Serum Luteinizing Hormone Research Articles

FRI283 Fragile X Gene Mutations Alter GnRH Neuron And Ovarian Innervation With Consequences On Reproductive Function

Abstract Disclosure: P.A. Villa: None. N. Lainez: None. C.R. Jonak: None. S. Berlin: None. I. Ethell: None. D. Coss: None. Mutations in the Fragile X messenger ribonucleoprotein 1 gene (FMR1) cause Fragile X syndrome, the most common cause of inherited mental disability, attributed to the loss of the Fragile X messenger ribonucleoprotein (FMRP). FMR1 mutations also comprise a majority of the genetic causes of premature ovarian failure (POF) in women, mechanisms of which are unknown. We utilized the Fmr1KO mouse model to determine the role of the FMR1 gene in the reproductive system in females. Similarly to what occurs in women harboring the mutation, our data demonstrate that Fmr1KO female mice experienced premature reproductive senescence, where reproductive function stopped at p163; in contrast, wild type controls stopped reproducing at p263. Since POF in women can occur due to either an insufficient pool of primordial follicles or early depletion of follicles, we quantified primordial follicles in 3 week old females and determined there was no difference between KO and controls. We then determined that Fmr1KO females had a higher number of corpora lutea at 8 weeks of age and gave birth to larger litters, suggesting that KO females recruit more follicles in each estrus cycle. Given that follicle stimulating hormone (FSH) and luteinizing hormone (LH) are essential in ovarian function, we analyzed gonadotropin levels in Fmr1KO females and determined they have higher serum LH and FSH. Inhibin b, progesterone, and testosterone levels were also higher, suggesting that high gonadotropins do not result from the lack of feedback. Ovariectomy determined that the hypothalamus drives high LH in KO females, while increased FSH is dependent on the ovaries. Increased vasculature in the corpora lutea and higher sympathetic innervation of developing follicles may increase steroid hormone production and drive increased serum FSH levels. To investigate the hypothalamic role in increased LH, we determined that a majority of gonadotropin-releasing hormone (GnRH) neurons express FMRP, which also have a higher number of GABAergic synapses in Fmr1KO females. Given that GABA is excitatory to GnRH neurons, alterations in afferent synaptic input can affect GnRH and LH secretion. LH pulsatile analysis determined higher LH pulse frequency in both unmodified and ovariectomized females, indicating an increase in GnRH neuron activity. In summary, our results reveal hypothalamic and ovarian contributions to the reproductive phenotype of Fragile X mutation carriers that may lead to early menopause. Presentation: Friday, June 16, 2023

Application value of tumor necrosis factor inhibitors in in vitro fertilization-embryo transfer in infertile women with polycystic ovary syndrome

BackgroundClinical value of tumor necrosis factor (TNF) inhibitors in in vitro fertilization-embryo transfer (IVF-ET) in infertile women with polycystic ovary syndrome (PCOS) was investigated in this study.MethodsA retrospective analysis was performed on the clinical data of 100 PCOS patients who received IVF-ET for the first time at Hebei Institute of reproductive health science and technology from January 2010 to June 2020. The patients were divided into Inhibitor group and Control group according to whether they were treated with or without TNF inhibitors. Next, the two groups were subject to comparison in terms of the days of gonadotropin (Gn) use, total dosage of Gn, trigger time, hormone level and endometrial condition on the day of human chorionic gonadotropin (HCG) injection, the effects of two different regimens on controlled ovarian hyperstimulation (COH) and pregnancy outcomes.ResultsThere were no significant differences in baseline characteristics between the two groups, including age, duration of infertility, body mass index (BMI), ovarian volume, antral follicle count, and basal hormone levels. Compared with the Control group, the days of Gn use and trigger time of patients in the Inhibitor group were significantly shortened, and the total Gn dosage was notably reduced. In terms of sex hormone levels on the HCG injection, the Inhibitor group displayed much lower serum estradiol levels while higher serum luteinizing hormone and progesterone (P) levels than the Control group. Notably, the high-quality embryo rate was also significantly increased with the use of TNF inhibitors. However, significant differences were not observed in endometrial thickness (on the day of HCG injection), proportion of endometrial A, B and C morphology (on the day of HCG injection), cycle cancellation rate, number of oocytes retrieved, fertilization rate, and cleavage rate between the two groups. Importantly, the clinical pregnancy rate in the Inhibitor group was significantly higher than that in the Control group, but there was no significant difference in the biochemical pregnancy rate, early abortion rate, multiple birth rate, ectopic pregnancy rate and number of live births between the two groups.ConclusionCollectively, after application of TNF-α inhibitor regimen, superior overall treatment effect can be observed in infertile PCOS patients receiving IVF-ET. Therefore, TNF inhibitors have certain application value in IVF-ET in infertile women with PCOS.

Evaluation of sex-related hormones and semen characteristics in reproductive-aged male COVID-19 patients.

In the past several months, the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐associated infection (coronavirus disease 2019 [COVID‐19]) developed rapidly and has turned into a global pandemic. Although SARS‐CoV‐2 mainly attacks respiratory systems, manifestations of multiple organs have been observed. A great concern was raised about whether COVID‐19 may affect male reproductive functions. In this study, we collected semen specimens from 12 male COVID‐19 patients for virus detection and semen characteristics analysis. No SARS‐CoV‐2 was found in semen specimens. Eight out of 12 patients had normal semen quality. We also compared the sex‐related hormone levels between 119 reproductive‐aged men with SARS‐CoV‐2 infection and 273 age‐matched control men. A higher serum luteinizing hormone (LH) and a lower ratio of testosterone (T) to LH were observed in the COVID‐19 group. Multiple regression analysis indicated that serum T: LH ratio was negatively associated with white blood cell counts and C‐reactive protein levels in COVID‐19 patients. It's the first report about semen assessment and sex‐hormone evaluation in reproductive‐aged male COVID‐19 patients. Although further study is needed to clarify the reasons and underlying mechanisms, our study presents an abnormal sex hormone secretion among COVID‐19 patients, suggesting that attention should be paid to reproductive function evaluation in the follow‐up.

Primary aldosteronism in Klinefelter's syndrome: two cases.

SummaryPrimary aldosteronism (PA) is more common than expected. Aberrant adrenal expression of luteinizing hormone (LH) receptor in patients with PA has been reported; however, its physiological role on the development of PA is still unknown. Herein, we report two unique cases of PA in patients with untreated Klinefelter’s syndrome, characterized as increased serum LH, suggesting a possible contribution of the syndrome to PA development. Case 1 was a 39-year-old man with obesity and hypertension since his 20s. His plasma aldosterone concentration (PAC) and renin activity (PRA) were 220 pg/mL and 0.4 ng/mL/h, respectively. He was diagnosed as having bilateral PA by confirmatory tests and adrenal venous sampling (AVS). Klinefelter’s syndrome was suspected as he showed gynecomastia and small testes, and it was confirmed on the basis of a low serum total testosterone level (57.3 ng/dL), high serum LH level (50.9 mIU/mL), and chromosome analysis. Case 2 was a 28-year-old man who had untreated Klinefelter’s syndrome diagnosed in his childhood and a 2-year history of hypertension and hypokalemia. PAC and PRA were 247 pg/mL and 0.3 ng/mL/h, respectively. He was diagnosed as having a 10 mm-sized aldosterone-producing adenoma (APA) by AVS. In the APA, immunohistochemical analysis showed co-expression of LH receptor and CYP11B2. Our cases of untreated Klinefelter’s syndrome complicated with PA suggest that increased serum LH levels and adipose tissues, caused by primary hypogonadism, could contribute to PA development. The possible complication of PA in hypertensive patients with Klinefelter’s syndrome should be carefully considered.Learning points:The pathogenesis of primary aldosteronism is still unclear.Expression of luteinizing hormone receptor has been reported in aldosterone-producing adenoma.Serum luteinizing hormone, which is increased in patients with Klinefelter’s syndrome, might contribute to the development of primary aldosteronism.

The effect of premature luteinizing hormone increases among high ovarian responders undergoing a gonadotropin‐releasing hormone antagonist ovarian stimulation protocol

To explore factors causing a premature rise in luteinizing hormone among high ovarian responders undergoing the gonadotropin-releasing hormone (GnRH) antagonist ovarian stimulation protocol. The present retrospective study included healthy women undergoing fresh cycles using a fixed GnRH antagonist protocol with a predicted high response and antral follicle count (AFC) of at least 15 at the Reproductive Medicine Center of Tongji Hospital, China, between January 1 and December 31, 2016. Treatment-related characteristics, hormone changes, and pregnancy outcomes were compared between patients who did or did not experience a premature luteinizing hormone rise. There were 314 patients included; 49 experienced premature luteinizing hormone increases. Among patients who experienced a premature rise in luteinizing hormone, a lower two pronuclear embryo rate (P=0.038); fewer high-quality embryos (P=0.020); higher serum luteinizing hormone (P=0.006), progesterone (P=0.013), and estradiol (E2) levels (P=0.003) on the day of human chorionic gonadotropin administration; a lower clinical pregnancy rate (P=0.031); and a higher cancellation rate (P=0.006) were observed. AFC of at least 22 (P=0.001) and E2 of 669pg/mL or higherat the start of GnRH antagonist administration were predictive of early (P=0.036) and late (P=0.033) premature luteinizing hormone increases. Earlier administration of GnRH antagonist could avoid premature luteinizing hormone increases among high ovarian responders, especially those with a starting AFC of 22 or more.

High luteinizing hormone weakens urinary continence mechanisms in association with prostaglandin E2 elevation in a postmenopausal rat model.

To explore the role of luteinizing hormone (LH) in the urinary continence mechanism, urethral function was investigated using a postmenopausal rat model with high serum LH concentrations and the postmenopausal rat model given a gonadotropin releasing hormone (GnRH) antagonist to lower LH concentrations. Adult female rats were divided into: 1) sham group; 2) ovariectomy group (OVX) with removal of bilateral ovaries; 3) OVX and GnRH-antagonist administered group (OVX + G); and 4) sham and GnRH-antagonist administered group (Sham + G). Urethral function was evaluated by the sneeze-induced urethral continence reflex experiment, and serum LH and prostaglandin E2 (PGE2) concentrations were measured. In the sneeze-induced urethral continence reflex experiment, urethral baseline pressure (UBP) and the amplitude of the urethral response during sneezing (A-URS) were measured. The UBP was significantly decreased in the OVX group than in the other groups. A-URS was significantly lower in the OVX group than in the Sham group, but with no significant difference compared with the OVX + G group. Lowering the serum LH by a GnRH-antagonist improved UBP to the same level as in the Sham group. The serum PGE2 concentration was significantly higher in the OVX group than in the other groups. The results suggested that the increased serum LH concentration in the OVX rat model worsened the continence mechanism. This mechanism is probably associated with an increased PGE2 concentration, because PGE2 caused urethral smooth muscle relaxation. A GnRH-antagonist might improve urinary incontinence by decreasing the serum LH and PGE2 concentrations.

Phoenixin-14 concentrations are increased in association with luteinizing hormone and nesfatin-1 concentrations in women with polycystic ovary syndrome

BackgroundPolycystic ovary syndrome (PCOS) is commonly characterized by obesity, insulin resistance (IR), hyperandrogenemia and hirsutism. Following the reported relationship between phoenixin-14 and gonadotropin production in rat hypothalamic-pituitary-gonadal axis, the present study was designed to investigate the circulating concentrations of phoenixin-14 and their associations with the concentrations of sex hormones including luteinizing hormone (LH), follicular stimulating hormone (FSH), estradiol (E2), progesterone (P4) and total testosterone (TT) in PCOS patients. MethodsA total of 41 women with diagnosed PCOS using Rotterdam criteria and 37 healthy individuals were enrolled in the study. ResultsSerum phoenixin-14 concentration in PCOS patients (n=41) was 0.515±0.044ng/ml, significantly higher than that in healthy controls (0.289±0.046ng/ml, n=37). PCOS patients had higher serum LH, dehydroepiandrosterone and fasting blood glucose concentrations, and higher index of homeostasis model of assessment-IR than those in healthy women. Correlation analysis showed significantly positive correlations of phoenixin-14 with LH, FSH, TT, P4, BMI and nesfatin-1 concentrations, and significantly negative correlations with E2 and serum insulin (FSI) concentrations, respectively. ConclusionsCompared to control women, PCOS patients had significantly increased serum phoenixin-14, LH and androgen concentrations. The positive correlations of phoenixin-14 concentrations with LH and TT concentrations suggest a possible role of phoenixin-14 in the development of PCOS.

AB68. Novel regulators of testosterone production

In recent years, interest in testosterone replacement therapy for the management of male hypogonadism has grown significantly. This development has paralleled increased public awareness of the signs and symptoms of hypogonadism (also known as low T or low serum testosterone) and the opportunity to address this problem with therapeutic interventions. Conventionally, medical treatment of hypogonadism has been met with various formulations of exogenous testosterone therapies, albeit such therapies do carry limitations. Limitations range from challenges with therapeutic delivery to possible adverse effects. As understanding has grown with respect to regulatory mechanisms of testosterone production and possible new targets for endogenous production of testosterone, new avenues are opening for consideration of therapy particularly in males with primary hypogonadism (low intratesticular testosterone, high serum luteinizing hormone (LH) with low serum testosterone). Several novel molecular pathways have received interest recently as potential pharmacologic targets to increase Leydig cell testosterone production. These pathways and/or signaling molecules include phosphodiesterases, the cholesterol translocator protein, the electron transport chain of mitochondria, cyclooxygenases and osteocalcin. The advantages of these new targets are suggested to be: (I) maintain an intratesticular testosterone environment that allows /promotes normal spermatogenesis, (II) avoid side effects of exogenous testosterone supplementation, and (III) maintain the negative feedback mechanism of luteinizing hormone (LH) that prevents testosterone levels from becoming supratherapeutic. These novel options are perceived to offer a more targeted and efficacious approach than other suggested interventions to stimulate Leydig cell testosterone production in individuals with primary hypogonadism, such as exogenous LH, human chorionic gonadotropin, and clomiphene, which all act conventionally through the LH receptor. The proposed novel targets offer opportunities to promote increased endogenous testosterone production through the Leydig cell directly without reliance upon functional LH receptors. This approach may involve the application of small molecules, dietary supplements, or even currently available FDA- approved medications, that may exploit newly refined understanding of signaling pathways at the Leydig cell level. It will be of interest to study all of these potential therapeutic prospects further both with careful animal model experimentation and subsequently in human clinical trials.

Luteinizing Hormone Levels Are Positively Correlated with Plasma Amyloid-β Protein Levels in Elderly Men

Dysregulation of the hypothalamic pituitary gonadal (HPG) axis during aging has been associated with increased risk of cognitive decline and developing dementia. Compared to controls, men with Alzheimer's disease (AD) have been shown to have lower serum testosterone levels and higher serum luteinizing hormone (LH) levels. As serum free testosterone concentration is negatively correlated with LH in older men, the independent contributions of these hormones to the pathogenesis of AD warrants further clarification. To explore this notion, we measured plasma amyloid-beta (Abeta), serum testosterone, serum LH and other biochemical parameters in 40 cognitively normal elderly men. Multiple linear regression analysis revealed that serum LH concentration is the only parameter that significantly correlates with plasma Abeta levels in these men (r=0.5, p=0.041). These results suggest that increased serum LH concentration, rather than lower serum free testosterone, is associated with the accumulation of Abeta in plasma. Larger, longitudinal human studies are needed to determine the significance of LH in the pathogenesis of AD.

Polymorphisms of the luteinizing hormone/chorionic gonadotropin receptor gene: association with maldescended testes and male infertility

Maldescended testes are the most common genital anomaly in newborns and are associated with testicular malignancy and infertility. As the inguinoscrotal phase of testis descent is androgen-dependent and requires integrity of the luteinizing hormone/chorionic gonadotropin receptor (LHCGR), we investigated whether nonsynonymous polymorphisms of the LHCGR gene are associated with maldescended testes. This was a retrospective case-control study including 278 patients with maldescended testes, 277 infertile men without maldescensus and 271 controls with normal sperm concentrations. Clinical and endocrinological workup of the patients was performed. Single nucleotide polymorphism (SNP) analysis was performed by GeneScan and TaqMan technology. Men with maldescended testes had significantly lower testis volumes, higher serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) but similar testosterone levels compared with both the control groups. The insLQ polymorphism in exon 1 (rs4539842) and the N291S SNP in exon 10 (rs12470652), showing increased receptor sensitivity in vitro, were not differently distributed between patients and controls. The S312N SNP in exon 10 (rs2293275) was significantly less frequent in men with maldescended testes than in controls. This difference was confirmed when infertile men with and without maldescensus were considered together. In men with maldescensus, a high LH drive maintains normal testosterone levels but this LH resistance is not associated with any particular LHCGR genotype. A significant association with the S312N polymorphism in exon 10 of the LHCGR is correlated to the spermatogenetic damage rather than to the maldescensus itself. Either the LHCGR itself or another genomic region linked to this SNP, possibly the germ cell-specific TFIIA-alpha/beta-like factor gene transcribed from the same genomic region in the opposite direction, is a risk factor for male infertility.

Sexual Function in Chronic Kidney Disease

Endocrine abnormalities are common in patients with chronic kidney disease (CKD) and lead to sexual dysfunction, anemia, hyperparathyroidism, and altered mineral metabolism. Common clinical problems include disturbances in menstruation in women, erectile dysfunction in men, and decreased libido and infertility in both sexes. Organic factors tend to be prominent and are related to uremia and other comorbid illnesses. Psychological factors and depression may exacerbate the primary problem. Alterations in the hypothalamic-pituitary axis are seen early in CKD and tend to worsen after patients start dialysis. Hypogonadism plays a dominant role in male sexual function, whereas changes in hypothalamic-pituitary function predominate in female sexual dysfunction. In patients on dialysis, treatment strategies include optimizing dose of dialysis, correction of anemia with erythropoietin, and correction of hyperparathyroidism. Successful kidney transplantation may restore normal sexual function, especially in younger patients.

Sexual dimorphism of GABA release in the medial preoptic area and luteinizing hormone release in gonadectomized estrogen-primed rats

We showed marked sex differences in the GABA outflow in the medial preoptic area of intact rats. To further determine the sexually dimorphic effects of estrogen on the GABA outflow, an in vivo microdialysis study was performed in gonadectomized rats 3–5 days after the estrogen- or cholesterol-priming. Dialysates and sequential blood samples (150 μl each) were simultaneously collected under freely moving conditions. Serum estradiol concentrations at 72 and 84 h after the estrogen capsule implantation were approximately 75 pg/ml in both sexes. Ovariectomized estrogen-primed (OVX+E 2) rats showed high GABA outflow from the late night through the morning, which was significantly declined until the onset of surge like secretion of luteinizing hormone (LH) in the afternoon ( N=7). Ovariectomized cholesterol-primed (OVX+C) rats consistently showed low GABA outflow and high serum LH concentration ( N=8). Conversely, orchidectomized estrogen-primed (ORX+E 2) rats showed high and episodic GABA outflow without any daily changes ( N=7), which was significantly greater than orchidectomized cholesterol-primed (ORX+C; N=8) and OVX+C rats. Only OVX+E 2 rats showed significant daily changes in the GABA outflow and serum LH concentration. Fitting with the double cosinor method demonstrated that the acrophase of the GABA outflow in OVX+E 2 rats occurs in the early morning, whereas the acrophases in OVX+C, ORX+C, and ORX+E 2 rats occur at various times of day. The present findings suggest that sex-specific effects of estrogen on the daily GABA release in the medial preoptic area may be involved in the sex difference of LH release in rats.

High serum luteinizing hormone and testosterone concentrations do not predict pregnancy outcome in women with recurrent miscarriage

Objective: To investigate the relationship between Day 8 serum luteinizing hormone (LH) and testosterone (T) concentrations, and body mass index (BMI) with pregnancy outcome in women with recurrent miscarriage. Design: Prospective observational study. Setting: National recurrent miscarriage clinic. Patient(s): Three hundred forty-four women (median age 32 years; range 18–44) with a history of recurrent first trimester miscarriage (median 4; 3–14; <12 weeks gestation) who conceived spontaneously and who received no pharmacological treatment during pregnancy were studied. All women were antiphospholipid antibody negative and had a normal peripheral karyotype as did their partners. Intervention(s): Outcome of untreated pregnancies. Main Outcome Measure(s): Day 8 serum LH and T concentrations and BMI were correlated with pregnancy outcome. Result(s): One hundred and ninety-two (55.8%) women had a live birth and 152 (44.2%) women miscarried. Polycystic ovarian morphology was diagnosed in 174 women (50.6%). There was no significant relationship between follicular phase LH concentrations and pregnancy outcome. Pregnancy outcome was similar in women with normal and high serum T concentrations. BMI value was not significantly different between women who had a live birth and those who miscarried. Conclusion(s): The analysis of this large cohort of women with recurrent miscarriage demonstrates that prepregnancy Day 8 serum LH and T concentrations, and BMI do not have a statistically significant relationship with pregnancy outcome.

Shrinkage in the horizontal dimensions of the vulva (vulvar shrinkage) as an indicator of standing heat in the beagle.

During the proestrous and estrous periods in 12 beagles, the following parameters were measured daily: the horizontal dimensions of the vulva, vaginal cytology, and serum luteinizing hormone (LH) and progesterone concentrations. Measurements of serum LH concentrations allowed for the identification of the LH surge and the optimal time for artificial insemination (AI). Nine out of the 12 beagles became pregnant through AI and completed a gestation. Shrinkage in the horizontal dimensions of the vulva (i.e., vulvar shrinkage) was primarily observed prior and subsequent to the LH surge. In six of the nine (66.7%) beagles that became pregnant, vulvar shrinkage was observed on the days in which the LH surge was confirmed, and the rate of vulvar shrinkage tended to be greater at higher serum LH concentrations. Further vulvar shrinkage was identified in all nine beagles within two days of the LH surge. An increase in the serum progesterone concentration was observed after the LH surge in each of the beagles that became pregnant, together with clinical signs of estrous behavior (i.e., standing heat) as well as a change in vulva condition from swollen to soft. This demonstrates that vulvar shrinkage is induced in response to the onset of the LH surge and that the LH surge can be predicted through the measurement of the horizontal dimensions of the vulva, vaginal cytology, and the assessment of serum progesterone concentrations in beagles.

Serum concentrations of follicle stimulating hormone and luteinizing hormone in normal girls and boys during prepuberty and at early puberty.

Serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) morning levels were determined in 327 normal prepubertal and early pubertal children of both sexes, utilizing a highly sensitive and specific microparticle enzyme immunoassay. Female (F) and male (M) prepubertal (Tanner's stage I) subjects were divided into 4 age groups: less than 3 months (F1, M1), 3 to 12 months (F2, M2) 12 to 24 months (F3, M3) and older than 24 months (F4 and M4). F pubertal subjects were classified in Tanner's stage breast II (F5) and III F6), while M pubertal subjects belonged to Tanner's stage genitalia II (M5). Serum LH levels were relatively low in prepubertal girls and showed a significant increment in group F6. By contrast, serum LH levels were relatively high in M1 and M2, decreased to levels similar to F in M3 and M4, and increased again at puberty in M5. Serum FSH levels were relatively high in girls of all prepubertal groups, even though they decrease significantly in M4. An increase was detected in pubertal group M6. All M prepubertal groups had significantly lower FSH levels than F prepubertal groups. The high serum LH of boys during the first year of life is probably a consequence of an activation of the hypothalamic GnRH pulse generator that is not apparent in girls. On the other hand, the high serum FSH of prepubertal girls is probably a consequence of a weak restraint influence of the prepubertal ovary on pituitary FSH secretion. This sexual dimorphism in gonadotropin secretion regulates, in a sex-specific fashion, prepubertal gonadal function in the two sexes.

Measurement of serum levels of exogenously administered FSH and LH during ovulation induction therapy.

We conducted a prospective study of blood levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) following daily intramuscular injection of human menopausal gonadotropin (hMG) containing equal proportions of FSH and LH. Blood samples were collected on alternate days and the resulting changes in the blood levels of the ovarian hormone estradiol were also monitored. Twenty-eight consecutive patients with polycystic ovary syndrome who were between the ages of 25 and 35 years and attending our infertility clinic for ovulation induction therapy and assisted pregnancy were studied. Polycystic ovary syndrome was diagnosed on laparoscopy and as evidenced by high serum LH which was three times greater than FSH in the follicular phase of the menstrual cycle. A male factor for infertility was excluded. Twenty-five out of 28 women (89.3%) receiving hMG responded to therapy by a rise in serum estradiol level (> 1200 pmol/l on day 9). Of the 25 women who responded to hMG, four had live single babies (16%). All four women showed a cumulative rise in mean serum FSH with treatment when measured by standard radioimmunoassay, reaching statistical significance on day 5 (p < 0.05). The remaining 21 who failed to become pregnant showed variable changes in mean serum FSH with a sharp rise on day 3 (p < 0.02) and a significant fall on day 7 (p < 0.02). However, mean serum LH measured by standard radioimmunoassay in all women remained unchanged throughout the period of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Polycystic ovary syndrome

Despite improved diagnostic facilities and advanced in vitro studies, the primary causes of the polycystic ovary syndrome (PCOS) have not been resolved. In addition to certain enzyme deficiencies causing a PCOS-like state, current evidence indicates altered functions of 5 alpha-reductase and cytochrome P450c17 alpha in PCOS patients as a group. However, it is not obvious if these are primary or secondary to the abnormal hormonal milieu. The relation of insulin-like growth factors (IGFs) to PCOS is of particular interest in view of the occurrence of IGF-II mRNA in the granulosa cells and the ability of IGF-I to regulate the granulosa cell and thecal-interstitial cell functions. In obese PCOS patients, the levels of sex hormone binding globulin and IGF-binding protein-1 are subnormal in serum, and fasting increases them. Fasting also suppresses high insulin and IGF-I concentrations in the same women. Growth hormone, regulated by insulin and probably by IGF-I, appears to be decreased in PCOS patients. Follicular growth, characteristically arrested in PCOS, is regulated by growth hormone to some extent, and growth hormone treatment has been found to improve the ovarian response to gonadotropins in some but not all anovulatory patients. In addition to the administration of growth hormone itself, therapeutic measures modulating the growth hormone-ovarian axis are being studied. High serum luteinizing hormone levels are typical of PCOS. These are often associated with infertility and early pregnancy loss. Lowering of the luteinizing hormone levels by a gonadotropin-releasing hormone analogue in combination with gonadotropins improves the outcome of pregnancies as compared with those achieved by clomiphene citrate. The use of the former regimen in PCOS patients may result in ovarian hyperstimulation. Ovarian electrocautery has proved to be effective in restoring cyclicity of ovarian function with a concomitant fall in luteinizing hormone and androgen levels. Interestingly, an increase in serum insulin secretion has been noted. It remains to be elucidated if this therapy, followed by decreased luteinizing hormone, is effective in reducing the elevated risk of miscarriages in women with PCOS.

High preovulatory serum luteinizing hormone level is unfavorable to conception

Serum estradiol, progesterone and luteinizing hormone (LH) levels of 16 pregnant and 58 non-pregnant stimulated in vitro fertilization-embryo transfer (IVF-ET) or gamete intrafallopian transfer (GIFT) cycles have been compared with regard to their predictive value for achievement of pregnancy. Serum estradiol and progesterone pattern of the pregnant and non-pregnant group did not show any significant difference. Around the time of ovulation induction by human chorionic gonadotropin (hCG) the serum LH values proved to be higher in the non-pregnant group than in the pregnant one. In spite of having a permissive function, preovulatory serum estradiol and progesterone seem not to have a predictive value with regard to pregnancy. Elevated preovulatory serum LH is detrimental for pregnancy, therefore the measurement of serum LH beyond hCG administration also, and the cancellation of cycles with high serum LH levels shortly before oocyte retrieval is recommended.

Dexamethasone Suppressible Hypergonadotropism in an Adolescent Patient with Prader-Willi Syndrome.

We report an adolescent patient with Prader-Willi syndrome accompanying suppressible hypergonadotropism. The subject is an 18-year-old female. She was obese (body mass index: 35.7) and hypomyotonic with mental retardation. On endocrinological examination, a high serum LH concentration and hyperresponsiveness of luteinizing hormone (LH) to intravenously administered LH-Releasing Hormone (LH-RH) were observed, while the basal follicle stimulating hormone level was within the normal range. In addition, serum dehydroxyepiandrosterone sulfate (DHEA-S) was also increased. Following 2 mg dexamethasone administration for 7 days, serum LH and DHEA-S were almost normalized and hyperresponse of LH to LH-RH completely disappeared. The present study provides evidence that altered responsiveness to adrenal steroid may be involved in the establishment of hypergonadotropinism in an adolescent patient with Prader-Willi syndrome.

Gonadotropin-releasing hormone sensitivity in underfed prepubertal female rats

Studies were conducted to investigate the effect of reduced food intake on pituitary gonadotropin-releasing hormone (GnRH) sensitivity as a possible link in the delay of puberty by underfeeding. Immature female rats (30-32 days old at the start of each experiment) were used throughout the study. Rats on reduced food intake (R) received 60% of normal food intake beginning at the age of 21 days, whereas control (C) animals were fed ad libitum. In ovariectomized (OVX), estradiol benzoate-progesterone-treated R rats, low doses (less than 5 ng/100 g body wt) of GnRH injected intravenously produced higher serum luteinizing hormone (LH) concentration than in comparable C rats. No difference was found at 5 ng GnRH but response to high doses (15 and 45 ng/100 g body wt) was sharply reduced in R rats. No difference in serum follicle-stimulating hormone concentrations was found. In contrast to the OVX-steroid treated animals, in intact R rats, GnRH evoked higher serum LH concentrations at both low and high doses. These studies indicate that reduced caloric intake can affect pituitary GnRH sensitivity and that the effect depends on both the dose of GnRH and the internal, gonadal steroid hormone milieu.