Relugolix: A Novel Gonadotropin-Releasing Hormone Antagonist for Prostate Cancer

Androgen deprivation therapy (ADT) is currently the mainstay of treatment for advanced prostate cancer. The peptide formulations of gonadotropin-releasing hormone (GnRH) antagonists need to be given subcutaneously every month. This led to the development of an oral, nonpeptide GnRH antagonist formulation relugolix which promptly lowers the levels of testosterone, luteinizing hormone, and follicular-stimulating hormone. On December 18, 2020, the US Food and Drug Administration approved relugolix for the treatment of adult advanced prostate cancer. The recommended loading dose of 360 mg on the 1st day of treatment, followed by 120 mg once daily orally, approximately the same time each day. The maximum plasma concentration (Tmax) is obtained within 2.25 h and is metabolized to a major extent by CYP3A mediated mechanism. Hot flushes, musculoskeletal pain, and fatigue are some of its common adverse effects. High rates of testosterone suppression with a limited adverse event profile make it an ideal therapy for the treatment of advanced prostate cancer.

Comparative evaluation of menstrual patterns and hormonal profiles in normal and abnormal perimenopause

Background: Currently there is only one marker to objectively establish perimenopause ie menstrual irregularities. Due to the wide variation in hormones like LH, FSH, estradiol, they become unreliable in predicting approaching menopause. This study was conducted to study and compare the patterns of LH, FSH and Estradiol in normal and abnormal perimenopause using the Stages of Reproductive Ageing Workshop (STRAW) criteria.Methods: A comparative evaluation was done after enrolling 200 patients out of which 100 women were in normal perimenopause (early-25 and late perimenopause-75, depending upon menstrual characteristics as defined by STRAW criteria) and 100 having AUB. Sociodemographic data, presence of menopausal symptoms were recorded. S. LH, S.FSH and S. estradiol we determined by adapted solid phase direct sandwich ELISA.Results: FSH was in menopausal ranges (>20IU/L) in early and late perimenopause. LH and FSH in women with AUB ranged from pre to post menopausal ranges. There was significant difference in LH and FSH between normal perimenopause and abnormal uterine bleeding. Estradiol levels showed a significant difference between late perimenopause and AUB p=0.015.Conclusions: This study shows that there is a progressive incremental trend in FSH and LH and decremental trend in Estradiol from early to late perimenopause due to decrease in ovarian follicular reserve, although the difference is not significant. Clinical symptoms present in 50% of late perimenopausal women showed that besides menstrual characteristics we can correlate these menopausal symptoms with raised FSH and low Estradiol. These women can be picked up and preventive therapy may be provided.

Endocrine Dysfunction in Recurrent Pregnancy Loss

Introduction: Miscarriage is the spontaneous loss of theconceptus before 20 weeks of gestation. Several disordersare known to contribute to recurrent miscarriage including:chromosomal anomalies; anti-cardiolipin antibodies;endocrine disorders such as poorly controlled diabetesmellitus; hyperprolactinaemia and thyroid diseases; andpelvic anatomic abnormalities. Study aimed to investigate theendocrine dysfunction in recurrent pregnancy lossMaterial and Methods: A prospective study comprising 70subjects was carried out. Fifty cases of recurrent abortionsconstituted the study group. Twenty healthy multipara femalesof same reproductive age group constituted the controlgroup. Venous blood samples were collected, and serum wasanalyzed for hormone analysis (T3, T4, TSH, LH, FSH, PRL,Testosterone) by ELISA method.Results: The mean prolactin level in cases of recurrentabortions was 19.96 ng/ml, while in controls was 11.77 ng/ml. The p value was 0.006 which was found to be statisticallyhighly significant. The mean TSH level in recurrent abortionscases was 5.81 mIU/L, while in controls was 1.95 mIU/L. Thep value was 0.004 which was found to be statistically highlysignificant.Conclusion: The patients with recurrent abortions hadsignificantly raised levels of TSH and Prolactin. Theprevalence of thyroid disorder and hyperprolactinemiawere higher in pregnant women with a history of recurrentabortion compared with healthy pregnant control population.Universal screening of pregnant females for endocrine profilecan improve the foetal outcome as well as social well-beingof females.

Kallman’s Syndrome in a Nigerian Boy: A Case Report

Background: Kallmann syndrome is a rare genetic hormonal condition of hypogonadotropic hypogonadism with a prevalence of 1 in 4000-10000 live born. It is often associated with anosmia or hyposmia. To the best of the author’s knowledge, it has not been reported in Nigerian literature. Methodology: The patient had been presented at the Endocrine and Metabolic Unit of our hospital, and was thus managed. The patient’s hospital records were reviewed and relevant data were extracted, with investigation results and clinical pictures presented. Ethical approval was obtained from the Institution Ethics review board. Results: We report the case of a 15-year-old boy who was presented with a small sized penis since birth, with only a slight increment since then. His developmental milestones were reportedly normal but he had the inability to smell. Examination revealed a well grown apparently healthy looking male, weighing 40 kg; with a normal height of 151.5 cm and BMI of 17.5 kg/m2. The testes were 1 ml each in volume with a stretched penile length of 3.5 cm. Laboratory investigation revealed low testosterone, luteinizing hormone, and follicular stimulating hormone. His karyotype was 46XY. He was commenced on 200 mg monthly injection of testosterone to which he made significant improvement as his penile length increased to 8.5 cm over 8 months of therapy, pubic hair also developed to Tanner 3 but his testicular volume remained pre-pubertal. He also reported that he could now smell. Conclusion: Kallmann syndrome though a rarely reported condition in the Nigerian population, could be treatable, though attainment of reproductive capability might require further intervention. A high index of suspicion and early treatment may yield a better outcome.

Basal luteinizing hormone and follicular stimulating hormone: is it sufficient for the diagnosis of precocious puberty in girls?

PURPOSE: A gonadotropin-releasing hormone stimulation test (GnRHST) is the gold standard in diagnosing central precocious puberty (CPP). The aim of this study was to investigate the diagnostic accuracy of basal gonadotropin levels for girls with suspected precocious puberty and to evaluate the factors affecting positive results of the GnRHST. METHODS: Korean girls with early pubertal development who visited the clinic during 2010-2012 were included. Auxological and biochemical tests were evaluated and a standard GnRHST was performed. A peak luteinizing hormone (LH) level of > or =5 IU/L was considered a positive response during the GnRHST. RESULTS: A total of 336 girls were included. The positive responses were observed in 241 girls (71.7%), and negative responses were found in 95 girls (28.3%). In the logistic regression analysis, the coefficient of the basal LH and basal LH/follicular stimulating hormone (FSH) ratio was 4.23 (P<0.001) and 21.28 (P<0.001), respectively. Receiver operating characteristic analysis showed that the basal LH/FSH ratio is a better predictor of the pubertal result after the GnRHST than the basal LH (area under the curve was 0.745 and 0.740, respectively; P=0.027). Among 189 girls with a basal LH of <0.1 IU/L, 105 (55.6%) had positive responses. CONCLUSION: An elevated level of the basal LH and basal LH/FSH ratio was a significant predicting factor of positive responses during the GnRHST. However a GnRHST was still necessary for diagnostic confirmation of CPP because more than half of the girls with a basal LH level below the detection limit revealed to have CPP.

Follicular stimulating hormone enhances Notch 1 expression in SK-OV-3 ovarian cancer cells / 부인종양

OBJECTIVE: Notch is known as a transmembranous receptor family with four homologous forms - Notch 1, Notch 2, Notch 3, and Notch 4 and related to cell fate regulation and angiogenesis. The purpose is to investigate the effect of follicular stimulating hormone (FSH) on the Notch 1 expression and proliferation in ovarian cancer cells. METHODS: Human ovarian cancer cell line, SK-OV-3 and FSH were used. XTT cell proliferation and cell migration assay were carried out with FSH 100 mIU/mL and Notch 1 siRNA. Western blots and reverse transcriptase-polymerase chain reactions (RT-PCR) were carried out to determine the expression level of the Notch 1 protein and mRNA with FSH treatment in 0, 1, 5, 10, 100, 200, 300 mIU/mL concentrations. Immunofluorescent (IF) stains were performed in SK-OV-3 cell cultures with FSH 100 mIU/mL. Student-t tests were used in statistical analyses. RESULTS: The SK-OV-3 have Notch 1 receptors in their natural status. FSH stimulated SK-OV-3 cells in XTT cell proliferation and cell migration assays and notch 1 siRNA inhibited. The expression level of Notch 1 protein and mRNA were increased in a dose dependent pattern according to FSH concentrations compared to untreated cells. IF stains also showed brighter Notch1 expressions in the FSH treated cells compared to the control cells. CONCLUSION: FSH enhances proliferation & migration and Notch 1 signaling in SK-OV-3 cells. The Notch signaling probably supports one of the cell proliferating mechanisms of FSH in ovarian cancer cells.

Sex Hormone Profiles in Spinal Cord-Injured Patients

OBJECTIVE: It is known that spinal cord injury (SCI) in adult men may result in sex hormonal changes. To investigate this change, we compared sex hormone levels of male SCI patients, uninjured normal, and infertile subjects. METHOD: Serum levels of follicular-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, testosterone were determined in 67 male SCI patients, 20 uninjured normal men and 39 idiopathic infertile men. One-way analysis of variance (ANOVA) procedures were performed with a significance level of 0.05. RESULTS: Compared with normal and infertile control groups, SCI patients had lower levels of testosterone and higher levels of prolactin. FSH levels of SCI patients were only lower than those of infertile controls. LH levels of SCI patients showed no significant difference. Compared with hormone levels of acute SCI patients, those of chronic SCI patients showed a tendency to increase in FSH, LH and testosterone, and a tendency to decrease in prolactin. Etiology of injury, completeness of injury and voiding method for neurogenic bladder did not influence the sex hormone levels in SCI patients. CONCLUSION: In our study, male SCI patients showed sex hormonal abnormalities of hypothalamo-pituitary type. And elevated serum prolactin level might influence hormonal changes and sexual dysfunction in male SCI patients.