Stimulated Gonadotropin Levels Research Articles

Assessment of gonadal functions in women with subclinical hypothyroidism in western Uttar Pradesh, India

Background: In females, hypothyroidism can cause menstrual disturbances mainly oligomenorrhea. Thyroid dysfunction has also been linked to reduced fertility and pregnancy complications. Several studies have been done to evaluate gonadal dysfunctions in overt hypothyroidism but very few studies are there regarding subclinical hypothyroidism. Present study evaluates the gonadal functions of women with subclinical hypothyroidism.Methods: Total 20 females of age 18 to 35 years with newly diagnosed subclinical hypothyroidism were taken as cases and 20 age and body mass index (BMI) matched healthy females were taken as controls. Both in cases and controls, basal FSH, LH, estradiol were measured on 3rd or 4th day of menstrual cycle at 8 AM on fasting. Thereafter Leuprolide 20 mcg/kg was given subcutaneously on the same day. One hour after injection, LH and estradiol were measured. Basal and stimulated values were compared between both groups.Results: Basal LH was significantly higher in controls (6.63±2.38 m IU/ml) when compared to cases (6.06±2.10 m IU) with a p value 0.01 (<0.05). No significant differences were found between stimulated LH and estradiol in both the groups.Conclusions: In mild thyroidal failure the response of pituitary gonadotrophs to leuprolide is normal in contrast to overt hypothyroidism where the response is sluggish. This is the first study to be done in subclinical hypothyroid subjects to asses both basal and stimulated gonadotropin levels. Further studies are required in large samples to confirm these findings.

MON-241 Relationship between Final Height and Birth Weight after Gonadotropin-Releasing Hormone Agonist Treatment in Girls with Central Precocious Puberty

Objectives: Small for gestational age (SGA) children may present an earlier onset of pubertal development, advanced bone maturation and reduced final height. The aim of this study was to compare the clinical parameters such as final adult height (FAH) and menarche with birth weight in girls with idiopathic precocious puberty (PP) treated with gonadotropin releasing hormone agonist (GnRHa). Subjects and methods: We retrospectively reviewed the medical records of 69 girls with PP who have reached FAH in a long-term trial of GnRHa treatment. The subjects were divided into SGA group and appropriated for gestational age (AGA) group. Anthropometric and endocrine parameters were obtained at diagnosis, at 6 months, and at cessation of GnRHa treatment. We investigated chronological age (CA), bone age (BA), BA / CA ratio, height and height SDS, predicted adult height (PAH-calculated with average table of BP method), PAH SDS, PAHa (calculated with advanced table of BP method), basal and stimulated gonadotropin levels, duration of treatment, duration of menarche, and FAH after treatment. The statistical significances of the clinical parameters between the two groups were compared. Results: The BA at the time of diagnosis was higher in SGA than in AGA (p <0.05). In the SGA, PAH SDS and PAHa were lower than those of AGA (p <0.05), but there was no significant difference in FAH between two groups. The FAH after GnRHa treatment was higher than PAH at diagnosis between SGA and AGA groups (p <0.05) . Body mass index was higher at the end of treatment in SGA group than in AGA (p <0.05). In addition, it was confirmed that the menarche was fast after treatment in SGA than in AGA (p <0.05). Target height, height SDS at diagnosis, PAH at diagnosis, and height SDS at end of treatment were found to be factors affecting FAH (p <0.05) . Conclusion: SGA girls with PP have increased bone age and rapid menarche than those of AGA group. But FAH after GnRHa treatment was not difference between the SGA and AGA groups. GnRHa treatment in SGA with PP may be helpful in improving FAH, and further large - scale studies will be needed in the future.

MON-247 Clinical Characterization of Female Peripheral Precocious Puberty Due to McCune-Albright Syndrome

Background: McCune-Albright syndrome (MAS) is a rare and sporadic disease caused by a post-zygotic mutation in GNAS1 gene. It is characterized by the classical triad of polyostotic fibrous dysplasia, café-au-lait skin spots and peripheral precocious puberty (PPP). However, clinical presentation of MAS is highly variable depending on mosaic tissue distribution of mutant-bearing cells. Due to the low prevalence of MAS, detailed data of clinical and laboratory presentation are scarce. Aim: To describe the clinical and hormonal features of PPP due to MAS from a single tertiary center. Patients and Methods: The medical records of girls with PPP due to MAS diagnosed and treated from 1990 and 2018 were systematically revised. We analyzed initial clinical presentation, Tanner stage, gonadotropins and estradiol levels, and pelvic ultrasound findings of a MAS cohort. Results: From a total of 37 patients (35 girls and 2 boys) with clinical diagnosis of MAS, 14 (37.8%) female patients presented PPP. The first clinical manifestation was thelarche in 12/14 (85.7%), followed by vaginal bleeding in 7/14 (50%), and pubarche in 5/14 (35.7%). The mean height (SDS) was 109 ± 35 cm (SDS: 1.3 ± 1.6). All girls had Tanner-staging ≥ B2 (ranging from B2-B4) and 8/14 (57.1%) had pubarche. Fibrous bone dysplasia was detected in 9/14 (64.2%) by bone scintigraphy and café-au-lait skin spots were found in 10/14 (71.4%) of these girls. Menarche occurred at mean age of 3.75 ± 2 yr (2 - 7.2 yr). Mean basal LH and FSH were 0.36 ± 0.24 IU/L and 1.27± 1.0 IU/L, respectively. Estradiol levels ranged from < 13 to 783 pg/mL (mean 96.8 pg/mL). Basal estradiol levels were at prepubertal range in 8/14 (57%) on several occasions. All girls underwent a GnRH-analogue stimulated test showing a prepubertal LH response (2.9 ± 2.1 IU/L); 2 patients showed completely suppressed basal and stimulated gonadotropin levels. Uni- or bilateral ovarian cysts were identified in 9/14 patients (64.2%) being bilateral in 50% of them. Mean ovarian volumes were 2.63 ± 1.4 cm³ for right and 2.05 ± 1.9 cm³ for left ovarian, with mean cyst volumes ranging from 2.7 to 45 cm3. Other endocrine hyperfunctions were not identified in this MAS cohort. Conclusion: PPP in girls with MAS has a heterogeneous clinical presentation. It was characterized by menarche at very early age as a first sign associated with variable values of estradiol levels (pre- and pubertal) and ovarian sizes. Pediatric endocrinologists must be aware of atypical clinical and laboratory presentation of PPP due to MAS.

Changing Etiological Trends in Male Precocious Puberty: Evaluation of 100 Cases with Central Precocious Puberty over the Last Decade

Background/Aims: There are few studies in the literature that have evaluated the etiological factors in boys with central precocious puberty (CPP), and these studies are limited in terms of the sample size. In the present study, we aimed to evaluate the etiological factors in male CPP cases. Methods: One hundred male CPP subjects, aged between 9 months and 10.5 years, were included. The medical records were screened, and age at diagnosis, bone age, body weight, height, pubertal stage, imaging findings of the pituitary gland, testosterone, and basal and stimulated gonadotropin levels were recorded. Results: There was no underlying cause in 74% of the cases, and an organic cause was determined in only 26%. Most of the organic cases had been diagnosed before the age of 7 years, whereas most of the idiopathic cases had been diagnosed after the age of 7 years. Conclusion: An organic cause was determined in 26% of the male patients with CPP. This rate is one of the lowest rates in the literature and indicates that the number of idiopathic male CPP cases is increasing over time. When a boy is diagnosed with CPP above the age of 7 years, the odds of detecting an underlying pathology are very low, and these cases are mostly idiopathic.

The Histrelin Implant: A Novel Treatment for Central Precocious Puberty

Standard treatment of central precocious puberty (CPP) consists of intramuscular or subcutaneous administration of a gonadotropin-releasing hormone (GnRH) agonist (GnRHa) at 3- to 4-week intervals. Although generally effective in suppressing clinical and laboratory parameters of puberty, GnRHa injections are painful, and the need for monthly clinic visits may contribute to poor compliance. Recently, a subcutaneous implant was developed that releases the GnRHa histrelin at an average rate of 65 microg/day. The aims of this study were to determine if a histrelin implant would suppress gonadotropin and estradiol (E2) in girls with CPP for 1 year and to compare the suppression to standard treatment. We studied 11 girls with CPP to determine if the histrelin implant can maintain long-term gonadotropin suppression. Mean age at diagnosis was 6 years (range: 2-9 years). GnRH (100 microg intravenously) stimulation tests (GnRH-STs) showed peak luteinizing hormone and follicle-stimulating hormone responses of 23 +/- 28 (mean +/- SD) and 20 +/- 25 mIU/mL, respectively. All subjects were initially treated with depot intramuscular GnRHa triptorelin embonate. Implants were inserted subcutaneously under local anesthesia, and depot GnRHa treatment was discontinued. Six girls were followed for 15 months after insertion (group A). For the remaining 5 girls, the implant was removed after 9 months, and a new implant was inserted at the same incision site (group B). GnRH-STs were performed before depot GnRHa treatment, immediately before implant insertion, at the 6- and 9-month visits for each patient and the 12- and 15-month visit for those girls followed for 15 months. In all girls, breast development regressed, growth velocity decreased, and bone-age advancement was slowed. Basal gonadotropins and their responses to GnRH-STs and E2 levels were suppressed. Peak luteinizing hormone and follicle-stimulating hormone responses to GnRH-STs at preinsertion versus 9 months were 1.30 +/- 1.34 vs 0.25 +/- 0.08 and 1.68 +/- 1.08 vs 1.13 +/- 0.55 mIU/mL, respectively. Basal and stimulated gonadotropin levels and E2 level remained suppressed in all 6 patients followed for 15 months after implant insertion. Patients and parents reported less pain and discomfort and less interference with school activity and work with the implant compared with standard monthly injections. The histrelin implant consistently suppresses clinical and laboratory parameters of puberty for 1 year and is a promising new technique for treating CPP without the pain and inconvenience of monthly injections.

A new DAX1 gene mutation associated with congenital adrenal hypoplasia and hypogonadotropic hypogonadism

We report on a DAX1 gene investigation in a patient with X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HH) in order to identify mutations causing this disorder and to confirm the clinical diagnosis. The description of the clinical course of the condition with a detailed documentation of longitudinal data is also reported. A male newborn was referred at 45 days of life because of vomiting, dehydration, and weight loss. The diagnosis was primary adrenal insufficiency. The appropriateness of glucocorticoid therapy during the prepubertal period was difficult to judge because of elevated ACTH levels on one hand and progressive retardation of bone age on the other hand. Basal and GnRH stimulated gonadotropin levels remained low during the entire period of examination and exogenous gonadotropin treatment was begun. This had to be interrupted at age 14.6 years because of the occurrence of a 3rd degree anaplastic ependimoma of the left posterior-parietal region, without apparent lepto-meningeal involvement. The molecular analysis of DAX1 gene of the propositus showed deletion of nucleotides AAT in exon 2, resulting in the loss of the Asn430. No alterations were found in the mother and grandmother. This deleted residue lies in one of the helices forming the hydrophobic core of the ligand-binding domain (LBD); thus this mutation may be the cause of the observed phenotype. Further investigations are needed to verify its causal role in AHC associated with HH.

Mild adrenal and ovarian steroidogenic abnormalities in hirsute women without hyperandrogenemia: Does idiopathic hirsutism exist?

To study ovarian and adrenal steroid profiles of women with idiopathic hirsutism, we compared sex steroid and basal and corticotropin (ACTH)-stimulated adrenal steroid levels before and after ovarian suppression induced by a long-acting gonadotropin-releasing hormone agonist analog (GnRH-a) in 24 hirsute women without hyperandrogenemia. Twelve healthy women served as controls for basal and ACTH-stimulated adrenal steroid levels. Serum levels of testosterone (T), sex hormone—binding globulin (SHBG), estradiol (E 2), basal and ACTH-stimulated 17-hydroxyprogesterone (17OHP), dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), Δ 4-androstenedione (Δ 4-A), 11-deoxycortisol (S) and cortisol (F), and basal and luteinizing hormone—releasing hormone (LHRH)-stimulated gonadotropin levels were measured before and 21 days after 3.75 mg intramuscular triptorelin in hirsute women. Basal T levels and basal and ACTH-stimulated Δ 4-A, DHEA, and DHEAS levels were not different in hirsute women with respect to controls. Basal and ACTH-stimulated 17OHP was elevated, and decreased to normal after ovarian suppression with triptorelin. Although basal and ACTH-stimulated Δ 4-A levels were normal, the ΔgD 4 -A Δ F and ΔgD 4 -A Δ 17OHP ratios were elevated and remained elevated after ovarian suppression, suggesting enhanced adrenal Δ 4-17,20-lyase activity. T, F, S, and DHEAS levels were not affected by ovarian suppression. Basal and ACTH-stimulated 17OHP and Δ 4-A, and stimulated DHEA concentrations were reduced with ovarian suppression, but their net increment and ratio to the increase of F in response to ACTH remained unchanged, reflecting the ovarian contribution to the secretion of these steroids. We conclude that idiopathic hirsute women with normoandrogenemia show an increase in ovarian secretion of 17OHP and a minimally increased adrenal Δ 4-17,20-lyase activity, suggesting that mild forms of ovarian a nd adrenal functional hyperandrogenism may be present in these patients with otherwise unexplained hirsutism.

Basal and stimulated gonadotropin levels in the perimenopause: Schmidt P.J.; Gindoff P.R.; Baron D.A.; Rubinow D.R. USA Am. J. Obstet. Gynecol. 1996 175/3I (643–650)

Basal and stimulated gonadotropin levels in the perimenopause: Schmidt P.J.; Gindoff P.R.; Baron D.A.; Rubinow D.R. USA Am. J. Obstet. Gynecol. 1996 175/3I (643–650)

Basal and stimulated gonadotropin levels in the perimenopause

OBJECTIVE: We investigated whether perimenopausal menstrual cycle irregularity is associated with increased gonadotropin immunoactivity, bioactivity, or the bioactivity/immunoactivity ratio at baseline and after short-term stimulation with gonadotropin-releasing hormone. STUDY DESIGN: Subjects consisted of four groups: (1) young regular cycling women (<35 years old), older women (>35 years) with (2) regular or (3) irregular menstrual cycles, and (4) postmenopausal women. Gonadotropin-releasing hormone stimulation tests (100 μg intravenous gonadotropin-releasing hormone) were performed in the National Institute of Mental Health outpatient clinic during the follicular phase of the menstrual cycle or randomly in postmenopausal women. RESULTS: Perimenopausal women had baseline follicle-stimulating hormone and luteinizing hormone levels and stimulated follicle-stimulating hormone levels (area under the curve) that were similar to those of postmenopausal women and significantly greater than those of control (younger and older) women. Postmenopausal women had significantly greater baseline levels of luteinizing hormone bioactivity than did the other three groups. The bioactivity/immunoactivity ratio in the postmenopausal women was significantly greater than those in the perimenopausal and older cycling women, which were similar. No change in the bioactivity/immunoactivity ratio was seen after gonadotropin-releasing hormone stimulation in any group. CONCLUSIONS: Although the perimenopause is associated with increases in baseline and stimulated gonadotropin levels similar to those seen after the menopause, significantly increased baseline luteinizing hormone bioactivity and the bioactivity/immunoactivity ratio are seen only after the menopause. (Am J Obstet Gynecol 1996;175:643-50.)

Hormonal Evaluation in Idiopathic Oligozoospermia: Correlation with Response to Clomiphene Citrate Therapy and Sperm Motility

The reported response of sperm count to clomiphene citrate therapy in subfertile males with idiopathic oligozoospermia has been widely variable. The author postulates that this may be due in part to patient heterogeneity that may be reflected in pretreatment hormonal status. Seventeen patients with idiopathic oligozoospermia (mean +/- SE sperm density of 7.3 +/- 1.2 x 10(6) sperm/mL, mean FSH of 5 +/- 0.5 IU/L) were studied. Pretreatment basal LH, FSH, testosterone, free T4, and prolactin levels as well as LHRH-stimulated LH and FSH levels were examined in relation to pretreatment semen parameters and percent change in sperm count after a mean of 7.2 +/- 0.6 months of clomiphene citrate therapy. The percentage of motile sperm correlated with basal LH (r = .59, p = .02, n = 16) and free T4 levels (r = .62, p = .02, n = 13). Clomiphene citrate therapy was associated with a significant increase in total sperm count (mean percent change 261 +/- 117, p = .02) and in total motile sperm count (mean percent change 370 +/- 216, p = .03). Percent change in total sperm counts and in total motile sperm counts correlated positively with pretreatment prolactin levels (r = .64, p = .007, n = 16, and r = .62, p = .01, n = 15), but not with the levels of other hormones. The results suggest that in patients with idiopathic oligozoospermia (1) clomiphene citrate therapy may be more effective in the subgroup of patients who have relatively higher prolactin levels, (2) basal and stimulated gonadotropin levels may not be helpful in predicting the response to clomiphene citrate therapy, and (3) lower sperm motility is associated with relatively higher free T4 and lower LH levels. The underlying mechanisms and the clinical utility of the current observations deserve further study.

Normal growth and normalization of hypergonadotropic hypogonadism in atypical Turner syndrome (45,X/46,XX/47,XXX)

A comparison has been made of a case with 45,X/46,XX/47,XXX mosaicism with some 50 cases in the literature. A significant positive correlation was found between height standard deviation scores of mosaic patients from the literature and the frequency of cells with a normal chromosome constitution (n = 21, rs = 0.552, P < 0.01). In contrast, a significant negative correlation was seen between body height and the frequency of cells with a 45,X constitution (n = 21, rs = -0.594, P < 0.01). There was no significant correlation of height standard deviation score with the 47,XXX cell line (n = 21, rs = -0.353). A patient with a rare chromosomal mosaicism (45,X/46,XX/47,XXX) is described. The diagnosis was first made by chromosome analysis in amniotic cells. The patient showed no symptoms suggestive of Turner syndrome and growth followed the 75th height percentile. Basal and gonadotropin-releasing hormone stimulated gonadotropin levels normalized after age 4.8 years and did not subsequently return to hypergonadotropic levels. In blood lymphocytes, there was an increase in the frequency of cells with a normal chromosome constitution over 9 years. This in vivo cell selection is discussed. Chromosome analysis in skin fibroblasts showed the same triple mosaicism with a similar distribution of cell lines as in blood lymphocytes. In conclusion, statistical evidence was demonstrated that the severity of short stature is correlated with the distribution of cell lines in 45,X/46,XX/47,XXX mosaicism. This finding is of importance for the genetic counselling in cases of prenatal diagnosis of mosaic Turner syndrome.

Basal and gonadotropin releasing hormone stimulated gonadotropin levels in the female red fox (Vulpes vulpes L.). Negative feedback of ovarian hormones during anoestrus

In the red fox, Vulpes vulpes L., an inhibition of gonadotropic function is observed in early anoestrus, particularly during lactation. During this period, secretion of progesterone as a result of the persistent corpora lutea after parturition and episodic releases of estradiol signify ovarian activity, suggesting involvement of these hormones in the modulation of pituitary hormones (luteinizing hormone (LH), follicle-stimulating hormone (FSH)). Effects of ovariectomy and (or) progesterone or estradiol treatments in vivo upon basal and gonadotropin releasing hormone (GnRH)-stimulated LH and FSH were observed. After ovariectomy, a great increase in the basal level of both gonadotropins and in GnRH-stimulated LH release, but not GnRH-stimulated FSH release, were observed. Progesterone treatment induced a decrease in GnRH-stimulated LH and FSH secretions and a decrease in basal LH and FSH levels in ovariectomized females. Estradiol treatment abolished basal secretions and GnRH responses for both hormones. These results suggest a negative feedback of both ovarian steroids at the hypothalamopituitary level on LH and FSH secretions during early anoestrus.

The effect of thyrotropin-releasing hormone stimulation on serum levels of gonadotropins in women during the follicular and luteal phases of the menstrual cycle

Thyrotropin-releasing hormone (TRH) can stimulate the secretion of adenohypophyseal thyroid-stimulating hormone and prolactin (PRL). The effect of TRH on gonadotropin secretion has not been well defined. This study investigated the effect of TRH administration on the peripheral levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) during the early follicular and midluteal phases of the menstrual cycle in five ovulatory, euthyroid, and normoprolactinemic women. Two hundred micrograms of TRH were administered intravenously on days 3 to 5 and on days 21 to 23 of the same cycle. LH and FSH were measured prior to and every 30 minutes for 2 hours following TRH injection. Ovulation was confirmed in all cycles by midluteal progesterone. All women had normal thyroid-stimulating hormone (TSH) and PRL responses to TRH stimulation in both cycle phases. Baseline and stimulated gonadotropin levels were analyzed by analysis of variance. Thirty minutes following TRH infusion, follicular and luteal levels of LH (mIU/ml, mean +/- standard error of the mean) significantly increased from 6.0 +/- 0.8 to 8.0 +/- 1.1 (P less than 0.005), and from 4.8 +/- 0.6 to 7.6 +/- 0.7 (P less than 0.005), respectively. Levels of FSH increased during both phases of the cycle, but the elevation was not statistically significant. These results suggest that TRH can stimulate gonadotrope secretion of LH, but not of FSH, in both the follicular and luteal phases of the cycle.

XY Gonadal Dysgenesis

Six patients with pure nonmosaic 46,XY gonadal dysgenesis (XY GD) and histocompatibility H-Y antigen titers in the normal male range (H-Y+) are presented. Clinical characteristics included a female phenotype, masculine skeletal characteristics, signs of virilization, and primary amenorrhea. All individuals had unambiguous female external genitalia, a hypoplastic uterus, bilateral tubes, and streak gonads. Histomorphologic evaluation of the gonads revealed various abortive testicular and ovarian elements capable of steroid production. Gonadal tumors were found in 4 patients (gonadoblastoma, dysgerminoma, granulosa cell tumor, myxofibroma). Plasma and urinary androgens and basal and stimulated gonadotropin levels were elevated prior to gonadectomy. Data show that the presence of the H-Y antigen per se does not guarantee normal testicular organogenesis. It is hypothesized that defective H-Y antigen binding to its gonadal receptors triggers aberrant testicular differentiation in 46,XY H-Y+ GD.

Effect of melatonin on the basal and stimulated gonadotropin levels in normal men and postmenopausal women.

The effect of melatonin on LH and FSH secretion in basal conditions and after stimulation with synthetic LHRH was studied in 3 volunteer normal men and 3 women two to five years after menopause. During the first three days of study, blood samples were obtained at 8 AM. On the second day, an iv injection of 50 mug LHRH was performed; on the third day, 2 ml of 0.9% saline were injected. In both cases, blood samples were obtained 30 and 60 minutes after the injection. On the fourth day, the subjects began melatonin (10 mg daily im for 13 days). Blood samples at 8 AM were obtained after 5, 11, and 13 days of administration of the drug. On days 5 and 11 of the treatment, iv injections of 50 mug LHRH were performed and on day 13 an iv injection of saline 0.9% was given. Blood samples were obtained 30 and 60 minutes after each injection. In each sample LH and FSH levels were determined by radioimmunoassay. Melatonin treatment did not cause any significant change in basal or post-stimulation LH and FSH levels either in men or in post-menopausal women. These results do not support previous findings of an insults do not support previous findings of an inhibitory effect of melatonin on gonadotropin secretion, even with the same dose as the one used in this study. Further studies with higher doses of melatonin are needed to clarify the action of this drug on gonadotropin secretion.