Pelvic ultrasound and pubertal attainment in girls with sexual precocity: the pivotal role of uterine volume in predicting the timing of menarche.

Introduction: Among girls assessed for pubertal precocity, pelvic ultrasound (pUS) may represent a pivotal tool to predict the time expected to elapse between sonographic assessment and the onset of menarche (TUS-M). Accordingly, the present analysis is meant to define the statistical relationship between sonographic parameters and TUS-M, in order to identify the most reliable predictor of the timing of menarche. Methods: Retrospective, multicenter analysis. Girls assessed for sexual precocity and showing sonographic and clinical findings consistent with pubertal onset upon referral were considered eligible. Patients treated with GnRH analogues were excluded and only those who had subsequently achieved complete and spontaneous pubertal attainment and for whom the exact date of menarche was available were included. Overall, we enrolled 184 girls from five tertiary care Italian Centers. Results: The time elapsed (months) between baseline endocrine assessment and spontaneous achievement of menarche showed a negative statistically significant correlation (p<0.0001) with LH (r:-0.61), FSH (r:-0.59), estradiol (r:-0.52) and stimulated LH values (r:-0.58). Among pUS parameters, ovarian volume (r:-0.17 left, -0.30 right) and uterine body-to-cervix ratio (r:-0.18) poorly correlated with TUS-M, while uterine diameters (r:-0.61 longitudinal, -0.64 anteroposterior) and volume (r:-0.70) achieved a highly statistical significance (p<0.0001). Uterine volume (UV) showed a negative logarithmic relationship with TUS-M and represented the most reliable predictor of the timing of menarche in uni- and multivariable analyses (p <0.001). ROC analyses identified the UV thresholds that best predict the onset of menarche within 18, 12 and 6 months, respectively: 3.76, 6.02 and 8.80 ml. Conclusion: The logarithm of UV shows the best statistical performance in predicting the timing of menarche in girls assessed for pubertal precocity. Accordingly, we developed a user-friendly online application that provides clinicians with an estimation of the months expected to elapse before menarche, based on the UV recorded upon pUS.

GnRH analogue triptorelin acetate induces ovulation in jennies during oestrus.

Most of the northern hemisphere donkey breeds are faced with the risk of extinction, thus donkey reproduction is considered an emerging branch of theriogenology, and the management of artificial insemination and induction of ovulation is a crucial point in setting up preservation protocols. For four consecutive cycles, six jennies' ovarian activity was routinely monitored; an ultrasound examination was performed daily from the evidence of a follicle diameter ≥27 mm until ovulation. Upon reaching a follicular diameter ≥32 ± 2 mm (Hour 0), oestrous jennies were treated alternatively with 0.1 mg triptorelin acetate, sc, (TRIP), 0.4 mg/sc of buserelin acetate (BUS) or saline, sc, (CTRL) and examined ultrasonographically at Hours 14, 24, 38, 42, 48, 62 and every 24 h until ovulation. Induction of ovulation was considered successful if ovulation occurred from 24 to 48 h after treatment. 11/12 cycles resulted in ovulation for TRIP and 12/12 for BUS and CTRL groups, respectively. Mean ± SD ovulation time after treatment was 37.3 ± 8.3, 47.1 ± 21.0 and 66.8 ± 25.9 h for BUS, TRIP and CTRL, respectively (p = .0032). Ovulation rates between h24 and h48 were 10/12 (83.3%) for both TRIP/BUS and 2/12 (16.7%) for CTRL, respectively (p = .003). Buserelin and triptorelin-treated jennies had a 25 times higher probability to ovulate between Hours 24 and 48 than controls (p = .003), while there were no jenny and cycle effects on the ovulatory rate. The results of this study show how triptorelin successfully induced ovulation in jennies, like other GnRH analogues previously evaluated.

The Visual Effect of a Down-Regulation With Dienogest and GnRH Analogues in Endometriosis: Lessons Learned From Two-Step Surgical Approach.

OBJECTIVE: To evaluate the intraoperative visual effect of treatment with GnRH-analogues and Dienogest in endometriosis. DESIGN: Retrospective observational study. SETTING: Every laparoscopy from all the different disciplines in our hospital is documented on video and stored in a database. The study was approved by the local ethics committee. A total of 193 patients with histological proven endometriosis from 2007 to 2021 were included, who underwent 2-step surgical procedure. Indications were endometrioma before CO2-Laser therapy, missing consent because of emergencies or other surgeries from other disciplines, or high active and extended disease. When endometriosis was suspected in a surgery conducted by other disciplines, a gynecological surgeon was called during the surgery. Data and intraoperative videos were reviewed by 2 independent reviewers at one referral center. Only cases with available video of first and second look laparoscopy were included. We excluded patient who had prior hormonal treatment in the last 6 months. Lesions were classified according to the description of Khan et al. Statistical analysis was performed using SPSS (Version 27.0, IBM). Mann-Whitney U test (nonparametric analysis) and χ2 tests were applied. Percentages were calculated for categorical variables and mean and standard deviation were calculated for continuous variables. Significance level was set to p <.05. INTERVENTIONS: Seventy-seven received GnRH-analogues and 116 Dienogest for preoperative hormone down-regulation. The median duration of down-regulation with GnRH-analogues or Dienogest was 3 months. The mean age was 32.3 (SD 6.3) years for GnRH-analogues and 32.6 (SD 6.3) years for Dienogest, p = .619 respectively. The visible intraoperative effect will be demonstrated in the video. CONCLUSION: The effect of a hormonal treatment can be observed macroscopically in endometriosis. This can help to understand the in vivo response to the administrated treatment. This video is showing our past experience, as performing second-look laparoscopy is not state of the art anymore.

Implication of biosignatures in the progression of endometriosis.

Endometriosis is an estrogen-dependent chronic inflammatory disorder involving the placement and growth of endometrial tissue outside the uterine cavity. It is the most common multifactorial disease that affects the life quality of women in reproductive age. Due to its multicomponent nature, early diagnosis of the disease is challenging. Since many genetic, epigenetic alterations and non-genetic factors contribute to the pathology of endometriosis, devising a drug therapy that directly acts on the ectopic tissue is extremely difficult. Endometriosis is a hormone-driven disease with estrogen considered as a primary driver for the development of endometriotic lesions. This study aims to identify biosignatures involved in endometriosis with and without gonadotropin releasing hormone agonists (GnRHa). GnRHa is a short peptide analog of GnRH that causes inhibition of estrogen and androgen synthesis. Microarray based-gene expression profiling was performed on total RNA extracted from endometriotic tissue samples with and without GnRHa-treated patients already published in our previous paper. The untreated group were considered as the control. Genes were then selected for validation by quantitative real-time polymerase chain reaction (qRT-PCR). qRT-PCR analysis confirmed significant downregulation in(p < 0.05) expression of DARC (p = 0.0042), CDH1 (p = 0.0027), CDH5 (p = 0.0283), ATP2A3 (p < 0.001), RGS5 (p = 0.0032), and CD36 (p = 0.0162) in endometriosis patients treated with GnRHa analogs. Although, CTNNAL1 (p = 0.0136) also showed significant results but there was upregulation in their expression levels after GnRHa treatment. Thus, an altered expression of these genes makes them a possible candidate determinant of endometriosis treated with GnRHa.

Combined Therapy with Anthracyclines and GnRH Analogues for Breast Cancer: Impact on Ischemic Heart Disease.

The combination of classic chemotherapy agents like anthracyclines with novel targeted medications has had a positive impact on women's survival from breast cancer. GnRH analogues are primarily employed to temporarily suppress ovarian function in premenopausal women with hormone-receptor-positive (HR+) breast cancer. Despite their benefits, the true degree of their collateral effects has been widely understudied, especially when it comes to ischemic heart disease. This review aims at summarizing the current state of the art on this issue, with particular focus on the risk for cardiotoxicity associated with the combined use of GnRH analogues and anthracyclines.

A Rare Case of Catamenial Pneumothorax and a Review of the Current Literature.

A 34-year-old female smoker, with a history of pelvic endometriosis, presented with initial symptoms of shortness of breath and a choking sensation. She was found to have a right pneumothorax on chest x-ray. Over the next eight months, she ultimately underwent three tube thoracostomies, two video-assisted thoracoscopic surgeries (VATS), wedge resection, and repeated pleurodesis due to pneumothorax recurrence. She was seen multiple times post-surgically with the focus of treatment being smoking cessation rather than contraceptive therapy, despite an early follow-up visit noting that the initial symptoms coincided with her menstruation. The purpose of this article is to bring attention to this rarely diagnosed condition. With added awareness and understanding of the underlying causes and available treatments, medical providers could likely spare many women from similar experiences and dramatically improve the quality of their lives.

Early preclinical work with gonadotropin-releasing hormone analogues.

In this article, I provide a narrative remembrance of the many early proof-of-concept studies that were performed at the Jones Institute for Reproductive Medicine in the late 1980s and early 1990s. A group, led by the late Dr. Gary Hodgen, piloted some of the ways gonadotropin-releasing hormone analogues are now being used clinically. We also put many different early peptide and small molecule (orally active) gonadotropin-releasing hormone antagonists through a battery of tests to explore their effects on male and female reproductive hormones. Most of the compounds we tested never reached the clinic because of various reasons. However, some have and are now making a difference in people's lives.

Primary Ovarian Leiomyoma in a White Tiger (Panthera tigris).

Ovarian leiomyomas are very rare in domestic cats and occasionally mentioned in studies reporting general pathological findings and neoplasm occurrence in non-domestic large felids. This report describes a case of ovarian leiomyoma in a 22-year-old white tiger (Panthera tiger), treated with deslorelin implants, detailing pathological and immunohistochemical characteristics. Gross examination revealed a markedly enlarged, firm, whitish right ovary with a multinodular appearance. On a cut surface, multiple brown-fluid-filled cysts interspersed with solid grey-to-white areas were observed. On histopathological examination, the ovary was enlarged and replaced by a densely cellular neoplasm composed of spindle cells arranged in fascicles, or occasionally in a herringbone pattern, embedded in a large stroma of collagenous connective tissue. Neoplastic cells showed mild nuclear atypia and pleomorphism and low mitotic rate. Immunohistochemistry confirmed smooth muscle origin of the neoplasm, and cells were positive for vimentin, alpha-smooth muscle actin, desmin, and caldesmon. A low rate (<1%) of Ki-67-positive cells was observed. Although rare, ovarian leiomyoma should be considered when a mass is present in the ovary of a tiger with reproductive failure. Because cancer of the reproductive system impacts on species conservation by affecting reproduction, regular health monitoring is warranted to support wildlife conservation. Finally, the adverse effects associated with long-term treatment with synthetic GnRH analogues as contraceptives in non-domestic felids are worthy of future investigation.

[Endocrine Treatments in Breast Cancer]. / Endokrine Therapien beim Mammakarzinom.

Endocrine Treatments in Breast Cancer Abstract. Breast cancer, the most common cancer in women, expresses estrogen and/or progesterone receptors in about 75% of patients. This allows for the use of endocrine treatments. Adjuvant therapy with tamoxifen for 5 years reduces the mortality by about 33%; the residual risk can be lowered by using aromatase inhibitors and by prolonging the treatment. In patients with advanced disease, the median duration of response to first-line therapy is about twelve months, and the median survival time is 20 to 40 months. The use of the various substances differs in terms of duration, sequence, and combinations, particularly with CDK4/6-inhibitors, depending on the clinical situation. Endocrine therapies are prescribed over a long period of time. Treatment adherence is improved by optimal control of side effects.

A Novel Compound Heterozygous Mutation of HSD17B3 Gene Identified in a Patient With 46,XY Difference of Sexual Development.

INTRODUCTION: Deficiency of the 17ß-hydroxysteroid dehydrogenase type 3 (17 ß-HSD3) is a rare autosomal recessive 46,XY Difference of sex development (DSD), resulting from pathogenetic variants in the HSD17B3 gene, which lead to absent or reduced ability to convert Δ4-androstenedione to testosterone in the fetal testes. AIM: This study aimed to present the clinical and genetic characteristics of an Italian patient receiving a diagnosis of 17 ß-HSD3 deficiency in adulthood. The patient was raised as female and underwent early surgical interventions to correct virilized genitalia, leading to a significant sexual distress. METHODS: At the time of the referral, a 20-gene Next Generation Sequencing custom-panel for DSD was performed on patient's genomic DNA. RESULTS: A novel compound heterozygous mutation in HSD17B3 gene was identified, detecting a new variant (c.257_265delAGGCCATTG, p.) CONCLUSION: Novel genotype causing 17 ß-HSD3 deficiency is presented. Furthermore, the patient's clinical history stresses the importance to actively involve these individuals in the decision-making process avoiding surgical intervention when the patient is not able to give fully informed consent. Cocchetti C, Baldinotti F, Romani A, et al. A Novel Compound Heterozygous Mutation of HSD17B3 Gene Identified in a Patient With 46,XY Difference of Sexual Development. Sex Med 2022;10:100522.

GnRH Analogues as a Co-Treatment to Therapy in Women of Reproductive Age with Cancer and Fertility Preservation.

In this review, we analyzed existing literature regarding the use of Gonadotropin-releasing Hormone (GnRH) analogues (agonists, antagonists) as a co-treatment to chemotherapy and radiotherapy. There is a growing interest in their application as a prophylaxis to gonadotoxicity caused by chemotherapy and/or radiotherapy due to their ovarian suppressive effects, making them a potential option to treat infertility caused by such chemotherapy and/or radiotherapy. They could be used in conjunction with other fertility preservation options to synergistically maximize their effects. GnRH analogues may be a valuable prophylactic agent against chemotherapeutic infertility by inhibiting rapid cellular turnover on growing follicles that contain types of cells unintentionally targeted during anti-cancer treatments. These could create a prepubertal-like effect in adult women, limiting the gonadotoxicity to the lower levels that young girls have. The use of GnRH agonists was found to be effective in hematological and breast cancer treatment whereas for ovarian endometrial and cervical cancers the evidence is still limited. Studies on GnRH antagonists, as well as the combination of both agonists and antagonists, were limited. GnRH antagonists have a similar protective effect to that of agonists as they preserve or at least alleviate the follicle degradation during chemo-radiation treatment. Their use may be preferred in cases where treatment is imminent (as their effects are almost immediate) and whenever the GnRH agonist-induced flare-up effect may be contra-indicated. The combination treatment of agonists and antagonists has primarily been studied in animal models so far, especially rats. Factors that may play a role in determining their efficacy as a chemoprotective agent that limits gonadal damage, include the type and stage of cancer, the use of alkylating agents, age of patient and prior ovarian reserve. The data for the use of GnRH antagonist alone or in combination with GnRH agonist is still very limited. Moreover, studies evaluating the impact of this treatment on the ovarian reserve as measured by Anti-Müllerian Hormone (AMH) levels are still sparse. Further studies with strict criteria regarding ovarian reserve and fertility outcomes are needed to confirm or reject their role as a gonadal protecting agent during chemo-radiation treatments.

Evaluation of pharmacological interventions in the management of adenomyosis: a systematic review.

PURPOSE: Medical management of adenomyosis largely revolves around symptom management, with very few drugs having received regulatory approval for the disease. However, the level of evidence supporting the use of pharmacological interventions is low, making it difficult to establish their efficacy in the treatment of adenomyosis. Hence, the aim of our systematic review is to identify the strength of evidence currently available and evaluate the effectiveness of different medical interventions in the management of adenomyosis. METHODS: The search was performed in MEDLINE, Embase, Cochrane Library, CENTRAL and ClinicalTrials.gov. Articles published between 1 January 2010 and 30 November 2020 were considered. Randomized controlled trials and observational studies that assessed the efficacy of medical interventions in patients with adenomyosis were included. The quality of the data was analyzed using RevMan 5.3 software. RESULTS: LNG-IUS (levonorgestrel intrauterine system), dienogest and gonadotropin-releasing hormone (GnRH) analogues were effective in reducing pain, uterine volume and menstrual bleeding. However, these data were largely obtained in the non-trial setting and were fraught with issues that included patient selection, short duration of therapy, small sample size, and limited long-term safety and effectiveness data. CONCLUSIONS: Although LNG-IUS, dienogest and GnRH analogues have better evidence for effectiveness in adenomyosis, the need of the hour is to thoroughly evaluate other novel molecules for adenomyosis using well-designed randomized controlled trials.

Preparation of Long-Acting Somatostatin and GnRH Analogues and Their Applications in Tumor Therapy.

Hormonal drugs are essential treatment options for some hormone-dependent or hormone- sensitive tumors. The common dosage forms of hormonal drugs have a short half-life. Hence, frequent administration is needed, which results in poor patient compliance. Nevertheless, using drug delivery technology, somatostatin analogues (SSAs) and gonadotropin-releasing hormone (GnRH) analogues are prepared into long-acting formulations that can significantly prolong the action time of these drugs, reducing medication frequency and increasing patient compliance. Such drugs are advantageous when treating acromegaly, gastroenteropancreatic neuroendocrine tumors (GEP-NETs), breast cancer, prostate cancer, and other diseases having a relatively long course. SSAs and GnRH analogues are two typical hormonal drugs, the long-acting formulations of which are essential in clinical practice. This review summarized the preparation methods and clinical application of long-acting formulations in cancer. Further, the action mechanism and new research of SSAs and GnRH analogues were discussed, and suggestions related to the development of long-acting SSAs and GnRH analogues were provided.

Goserelin Ovarian Ablation Failure in Premenopausal Women With Breast Cancer.

Breast cancer is the most prevalent cancer known worldwide in women. It is a heterogeneous, phenotypically diverse disease composed of several biologic subtypes that have distinct behavior and response to therapy. Hormone receptor-positive (i.e., estrogen [ER] and/or progesterone [PR] receptor-positive) breast cancers comprise the most common types of breast cancer, accounting for 75% of all cases. This makes endocrine therapy the standardized treatment for patients with ER+/PR+ breast cancer. Drugs that block estrogen receptors or that lower estrogen levels are the mainstay of treatment. High-risk patients benefit from the addition of ovarian function suppression (OFS)/ablation to either an aromatase inhibitor (AI) or tamoxifen. This case report discusses a 36-year-old premenopausal female who presented with an abnormal right breast lump in the upper outer quadrant of the right breast. Due to high suspicion of malignancy, a biopsy was performed which showed features of both lobular and ductal carcinoma with ER and PR positivity, HER 2 was negative. The patient underwent mastectomy with axillary lymph node removal due to concern for multifocal disease. No clinically relevant genetic mutations were present. Oncotype DX breast recurrence score was 16 and no chemotherapy was offered. Due to large tumor size, young age OFS with goserelin 3.6mg/28 days and letrozole 2.5 mg once daily was recommended. After 16 months of treatment, the patient developed a failure of goserelin-induced ovarian suppression. This case report highlights the possibility of the development of hormonal resistance after long-term use of goserelin.

Estrogens in polycystic liver disease: A target for future therapies?

BACKGROUND AND AIMS: Patients suffering from polycystic liver disease (PLD) can develop large liver volumes, leading to physical and psychological complaints, reducing quality of life. There is an unmet need for new therapies in these patients. Estrogen seems to be a promising target for new therapies. In this review, we summarize the available experimental and epidemiological evidence to unravel the role of estrogens and other female hormones in PLD, to answer clinical questions and identify new targets for therapy. METHODS: We identified all experimental and epidemiologial studies concerning estrogens or other female hormones and PLD, to answer pre-defined clinial questions. RESULTS: Female sex is the most important risk factor for the presence and severity of disease; estrogen supplementation enhances liver growth and after menopause, liver growth decreases. Experimental studies show the presence of the estrogen receptors alfa and beta on cystic cholangiocytes, and increased in vitro growth after administration of estrogen. CONCLUSIONS: Based on the available evidence, female PLD patients should be discouraged from taking estrogen-containing contraceptives or hormone replacement therapy. Since liver growth rates decline after menopause, treatment decisions should be based on measured liver growth in postmenopausal women. Finally, blockage of estrogen receptors or estrogen production is a promising target for new therapies.

Gonadotropin-releasing hormone stimulation test and diagnostic cutoff in precocious puberty: a mini review.

The gonadotropin-releasing hormone (GnRH) stimulation test is a valuable tool in diagnosing and differentiating causes of early pubertal occurrences. Utility of the test can be limited in some instances, however, including the early phases of pubertal hypothalamic-pituitary-gonadal axis activation, in girls showing commonly overlapping pictures, and in obese children due to excess circulating estrogen that suppresses luteinizing hormone (LH). A lack of consistent baseline and stimulated gonadotropin cutoffs observed in different studies also contributes to limitations in testing. Nevertheless, early detection of true pathological causes for pubertal disorders is needed to allow prompt treatment and better prognosis. While basal LH can be beneficial as a good screening tool for detecting pubertal disorder, it does not preclude the need for GnRH testing. The aim of this review was to highlight the role of GnRH stimulation tests and varying testing cutoffs in diagnosis of precocious puberty and its classification.

Combined therapy with GnRH analogue and growth hormone increases adult height in children with short stature and normal pubertal onset.

OBJECTIVE: To investigate whether gonadotropin releasing hormone analogue (GnRHa) combined with recombinant human growth hormone (rhGH) can improve the adult height (AHt) of children with short stature and normal pubertal onset. METHODS: In this retrospective study, GnRHa/rhGH treatment was given to children with normal pubertal onset and short stature. Patients were followed up to measure their AHt. The primary outcomes were the disparity between AHt standard deviation score (AHt SDS) and pre-treatment height standard deviation score (Ht SDS) and the disparity between AHt and target height (THt). RESULTS: A total of 94 patients were included. Forty-nine boys were treated with GnRHa/rhGH for 24.84 ± 13.01 months, and 45 girls were treated for 23.89 ± 10.43 months. (2) Before treatment, the Ht SDS of boys and girls was -1.82 ± 1.30 and -1.10 ± 1.61, respectively, and the target height was 168.98 ± 3.51 cm and 157.90 ± 3.25 cm, respectively. (3) After treatment, for boys, the AHt SDS increased by 1.37 ± 1.28 (p = 0.000) and the disparity between AHt and THt was 0.98 ± 6.18 cm (p = 0.273); for girls, the AHtSDS increased by 1.28 ± 1.48 (p = 0.000), and the disparity between AHt and THt was 3.64 ± 4.86 cm (n = 45, p = 0.000). (4) Subgroup analysis showed that, for boys with idiopathic short stature (ISS) and non-ISS, AHt SDS increased by 2.00 ± 1.16 (p = 0.000) and 0.71 ± 1.06 (p = 0.003) respectively, compared with the pre-treatment HtSDS; The disparities between AHt and THt were -0.70 ± 6.54 cm and 2.73 ± 5.37 cm respectively. For girls with ISS and non-ISS, AHtSDS increased by 2.73 ± 1.21 (p = 0.000) and 0.748 ± 1.19 (p = 0.001), respectively; AHt increased by 2.63 ± 6.12 cm (p = 0.165) and 4.02 ± 4.37 cm (p = 0.000) compared with THt, respectively. (5) Multiple linear regression analysis showed that the baseline bone age (BA) (ß = -0.200, p = 0.003), basal IGF-1(ß = -0.002, p = 0.008) and HtSDS (ß = -0.679, p = 0.000) had negative effects on increment of AHtSDS. CONCLUSION: For adolescents with normal pubertal onset and short stature, with or without ISS, GnRHa/rhGH therapy can effectively improve AHtSDS. After treatment, ISS adolescents can reach the THts, and Non-ISS adolescents can exceed their THts.

Case Report: A Case of Intellectual Disability with Inappropriate and Challenging Sexual Behavior that was Treated with GNRH Analogues.

Intellectual Disability starts within the course of developmental stages and covers both intellectual and adaptive deficiencies in conceptual, social and applied fields. Individuals with intellectual disability experience many difficulties in social life due to challenging and inappropriate sexual behaviour. Suchdifficulties need to be addressed, reduced or treated. Traditional treatments often fail to treat and improve suchbehavior. Alternative treatment options need to be explored with studies conducted in this field. With this paper, we aimed to show and touch on alternative treatments for challenging and inappropriate behaviors of a 15-year old boy with intellectual disability, who was treated with GNRH analogues.

Diagnostic value of urinary luteinizing hormone levels in the monitoring of precocious puberty treatment

ABSTRACT Objective To determine whether first-voided urinary LH (FV-ULH) - level measurement can adequately assess pubertal suppression as much as standard tests can. Subjects and methods The study group included patients with central precocious puberty and rapidly progressing early puberty who received up to 3 - 4 doses of GnRHa therapy monthly and did not have adequate hormonal suppression after GnRH stimulation (90-minute LH level > 4 IU/L). Design: All of the participants underwent an LHRH test just after admission to the study. According to the stimulated peak LH levels, the patients were divided into 2 groups and followed until the end of the first year of treatment. The concordance between FV-ULH and stimulated LH levels was assessed. Results The FV-ULH levels in patients with inadequate hormonal suppression were significantly high compared to patients with adequate hormonal suppression. FV-ULH levels were very strongly correlated with stimulated LH levels (r = 0.91). Its correlation with basal LH levels was significant (r = 0.65). However, this positive correlation was modestly weakened after the first year of treatment. The cutoff value for FV-ULH of 1.01 mIU/mL had the highest sensitivity (92.3%) and specificity (100%). Conclusion FV-ULH levels, using more reliable and sensitive assay methods, can be used to monitor the adequacy of GnRHa therapy.