High Gonadotropin Levels Research Articles

P-33 PRIMARY OVARIAN INSUFFICIENCY AS A COMPONENT OF AUTOIMMUNE POLYGLANDULAR SYNDROME

Abstract Introduction Primary ovarian insufficiency (POI) is characterized by amenorrhea secondary to ovarian dysfunction accompanied by high gonadotropin levels in women before the age of 40. Autoimmunity is estimated to account for 5-17% of POI etiologies. Although it varies according to its subtype, the prevalence of POI in patients with autoimmune polyglandular syndrome (APS) is reported to be between 16% and 40%. It may take several years to recognize the syndrome. Generally, a multidisciplinary approach is needed to diagnose and treat the cases accurately. The present case report described the diagnostic process of such a patient. Clinical Case A 19-year-old female patient applied to our outpatient clinic with the complaint of disruption of menstrual cycles for nine months. She was diagnosed with type 1 diabetes mellitus and chronic autoimmune thyroiditis for nine years and was receiving insulin glargine, insulin aspart, and levothyroxine treatment. She reported that her menarche age was 12 years, and she had regular menstrual cycles until the previous year; it was learned that she first experienced oligomenorrhea and then amenorrhea for nine months. Her body mass index was within normal limits on examination, and secondary sex characteristics were fully developed. Laboratory tests revealed fasting plasma glucose 180 mg/dL, HbA1c: 9.5%, TSH: 2.2 mIU/L, free T4: 1.4 ng/dL, Anti-TPO: 120 IU/mL, (<34), prolactin: 18 mcg/L, basal serum cortisol: 15 mcg/dL. β-hCG was negative. Karyotype analysis was determined as 46, XX without structural chromosomal abnormality. Following the progesterone challenge test, the patient had no bleeding, and serum FSH level, which was checked twice, was high, serum estradiol was low, and AMH was also low at 0.1 ng/mL. The patient was diagnosed as POI based on this clinic and laboratory features. Bone density was found to be within normal limits in bone densitometry. The patient, who currently does not seek fertility and does not consider oocyte freezing, was started on hormone replacement therapy with transdermal estradiol and oral micronized progesterone. Conclusion POI is rarely seen in women before the age of 30, but patients with APS should be screened and closely followed up to identify other organ dysfunctions that may be targets of the immune system. When POI is diagnosed at an early age, attention should be given to other accompanying autoimmune diseases and polyglandular syndrome.

Retroperitoneal ectopic pregnancy from a tertiary obstetrics hospital in Vietnam: A case series and literature review.

Retroperitoneal ectopic pregnancy is an uncommon condition in clinical practice, often associated with misdiagnosis and unconventional treatment. Delayed interventions can lead to poor prognosis and sometimes catastrophic situations. Due to the limited number of reported cases in the literature, an established treatment protocol has yet to be introduced. This case series presents three instances at a tertiary women's hospital in Vietnam. In cases 1 and 2, a single approach-either surgery or a chemo-regimen-was applied. However, the third patient was treated with a combination of both therapies. This series highlights an evolution in management, progressing from incomplete removal of the gestation to a comprehensive combination of surgery and chemotherapy. Additionally, high serum beta-human chorionic gonadotropin (β-hCG) levels and suspicious ultrasound and magnetic resonance imaging (MRI) findings are crucial for establishing the diagnosis.

Older adult women with chronic anorexia nervosa: heterogeneous adaptation to undernutrition over time.

Anorexia nervosa (AN) in older adult women is primarily described through reviews or case reports focusing on psychiatric traits, with no comprehensive studies evaluating their complete nutritional and hormonal profiles. This study aimed to describe a group of women with anorexia nervosa aged above 35 years old (AN35), and compare them with young women with anorexia nervosa (ANY) and normal-weight control participants. Anthropometric, metabolic, nutritional, and psychiatric parameters were collected and compared among three groups of women: 50 AN35, 37 ANY, and 38 controls. AN35 exhibited a mean disease duration of 271 ± 19 months, with 94% chronic forms and 58% restrictive types. Despite having similar BMI as ANY, AN35 displayed more altered parameters, including higher liver enzymes (p = 0.007), free T3 (p = 0.0046) and leptin (p < 0.0001); and lower albumin (p = 0.0029), and white cells (p < 0.0001). AN35 showed significant heterogeneity in hormonal adaptation, such as free T3. Half of the patients aged above 51 years revealed high gonadotropin levels despite being undernourished. Additionally, AN35 groups presented with 50% of bones fractures, decreased T-scores under -2.5 (p < 0.0001 for femoral), and altered micro architectural HRPQT parameters compared to ANY. Anorexia nervosa in older adult women is predominantly chronic. Nutritional parameters changes with age suggests a significant heterogeneity and possible adaptation of energy balance and bodyweight set point for others. Complications may be severe, altering the quality of life, and sometimes potentially lethal. These findings highlight the potential adaptation of energy balance with age, and should assist clinicians in clinical practice.

Exome Sequencing to Identify Novel Variants Associated with Secondary Amenorrhea and Premature Ovarian Insufficiency (POI) in Saudi Women.

Post-pubertal disappearance of menstrual cycles (secondary amenorrhea) associated with premature follicular depletion is a heterogeneous condition. Patients with this disease have low levels of gonadal hormones and high levels of gonadotropins. It is one of the causes of female infertility and a strong genetic component is attributed as an underlying cause of this condition. Although variants in several genes have been associated with the condition, the cause of the disease remains undetermined in the vast majority of cases. Methodology and Materials: Ten Saudi married women experiencing secondary amenorrhea were referred to a center for genetics and inherited diseases for molecular investigation. A family-based study design was used. Intensive clinical examinations, including pelvic ultra-sonography (U/S) and biochemical evaluations, were carried out. Karyotypes were normal in all cases and polycystic ovarian syndrome (PCOS) was excluded by using Rotterdam consensus criteria. Patients' DNA samples were whole-exome sequenced (WES). Bidirectional Sanger sequencing was then utilized to validate the identified candidate variants. The pathogenicity of detected variants was predicted using several types of bioinformatics software. Most of the patients have a normal uterus with poor ovarian reserves. Exome sequence data analysis identified candidate variants in genes associated with POI in 60% of cases. Novel variants were identified in HS6ST1, MEIOB, GDF9, and BNC1 in POI-associated genes. Moreover, a homozygous variant was also identified in the MMRN1 gene. Interestingly, mutations in MMRN1 have never been associated with any human disease. The variants identified in this study were not present in 125 healthy Saudi individuals. WES is a powerful tool to identify the underlying variants in genetically heterogeneous diseases like secondary amenorrhea and POI. In this study, we identified six novel variants and expanded the genotype continuum of POI. Unravelling the genetic landscape of POI will help in genetic counselling, management, and early intervention.

Alzheimer’s Disease and Premature Ovarian Insufficiency

Estradiol promotes neuronal growth, transmission, survival, myelinization, plasticity, synaptogenesis, and dendritic branching and it improves cognitive function. Alzheimer’s disease (AD) is characterized by amyloid plaques, neurofibrillary tangles, and the loss of neuronal connection in the brain. Genomic analysis has concluded that hypoestrogenism influences the APOE gene and increases the risk of AD. Premature ovarian insufficiency (POI) is defined as oligo/amenorrhea in women below 40 years of age, low estradiol, and high-gonadotropin levels. Early symptoms and signs of POI must be detected in time in order to prevent subsequent complications, such as Alzheimer’s disease. Meta-analysis has shown favorable effects of estrogen in preventing Alzheimer’s. We measured some of the typical markers of AD in women with POI such as interleukin 6 (IL-6), interleukin 8 (IL-8), tissue necrosis factor α (TNFα), TAU1, TREM2, and amyloid precursor proteins (APP). While FSH, LH, and IL-8 were significantly higher in POI group, compared to controls, testosterone and DHEAS were lower. A significant decrease in IL-6 was found in the POI group during a 6-month therapy, as well as an increase in amyloid precursor proteins. CONCLUSION: Neurological complications of POI, such as declining short-term memory, cognitive function, and dementia, have to be promptly stopped by initiating estro-progestogen therapy in POI. A long-term continuation of the therapy would be strongly advised.

A Case of Metastatic Choriocarcinoma With Intracerebral Hemorrhage Caused by a Ruptured Pseudoaneurysm

A rare cause of cerebral hemorrhage is the metastasis of choriocarcinoma from gynecology. Herein, we report a case of a patient with brain metastasis of choriocarcinoma with cerebral hemorrhage. A 14-year-old female who had undergone surgery for a hydatidiform molar pregnancy presented with a disturbance of consciousness due to cerebral hemorrhage. Imaging studies revealed the presence of a cerebral aneurysm and several mass lesions in the lung field, and high serum beta-human chorionic gonadotropin level was confirmed. Thus, we suspected cerebral hemorrhage caused by brain metastasis of choriocarcinoma. She went into a coma, and an emergency craniotomy was performed to remove the hematoma and aneurysm. The pathology of the aneurysm was pseudoaneurysm due to the rupture of the vascular wall caused by increasing metastatic cells from choriocarcinoma in the cerebrovascular wall. Therefore, multidrug chemotherapy was immediately initiated. The choriocarcinoma, including the metastatic lesions, is in remission. To improve the outcome of choriocarcinoma, it must be diagnosed early, and treatment should be immediately started. Moreover, neurosurgeons should be aware of such diseases and consider them as one of the differential diagnoses, particularly in females of reproductive age with cerebral hemorrhage.

ODP431 Adiposity in menstrual dysfunction and the role of laboratory testing in diagnosis

Abstract Adiposity significantly contributes to reproductive function. Whereas lower body weight is strongly associated with increased risk of functional hypothalamic amenorrhea (FHA), the relationship between BMI and the timing of menopause is poorly understood. Recent studies of self-reported data suggest women with BMI&amp;lt;18.5kg/mg 2 have a significantly higher risk of menopause before age 45 years. However, without confirmatory testing, there is the possibility of misdiagnosis of menopause given the prevalence of FHA in low-weight women. Although FHA and menopause are clinically identical, laboratory evaluation could potentially aid in differentiating the two entities, as menopause is characterized by high gonadotropin levels, whereas FHA is characterized by low-normal gonadotropin levels. Given the increased morbidity and mortality associated with early age of menopause, this distinction is clinically important. We sought to identify age of menopause in low-weight women using clinically available data at a large, academic health system. We hypothesized that women with a BMI&amp;lt;18.5kg/m 2 would have a lower age of menopause but that confirmatory diagnostic testing to differentiate menopause from FHA would be infrequently performed. The study was conducted by retrospective chart review of the electronic medical records of 3,000 women &amp;gt;50 years of age and BMI&amp;lt;18.5kg/m 2 . After exclusion of individuals with no date of menopause, BMI&amp;gt;18.5 kg/m 2 at the menopausal transition and history of known cause of early menopause, 239 charts were included in the analysis. Participants had a median BMI of 17.7kg/m 2 at the final menstrual period (FMP). Median age at the FMP in all low weight women with BMI&amp;lt;18.5kg/m 2 was 51 years. There was a positive correlation between age of the FMP and BMI (rho=0.13, p=0. 04). When stratified by BMI, age of the FMP decreased with decreasing BMI. For women with a BMI of 18-18.49kg/m 2, FMP occurred at a median age of 51 years; for women with a BMI of 16-17.99 kg/m 2, FMP occurred at a median age of 50 years; and for women with BMI&amp;lt;16kg/m 2, FMP occurred at a median age of 48 years. Only 30 women (12.6%) included in the study had an FSH level measured after diagnosis of menopause and eight of these women (26.67%) had an FSH&amp;lt;18 (range: 0.7-14.7 IU/mL), which is lower than expected for menopause. Therefore, these data, obtained from clinical data rather than self-report, provide further evidence that low-BMI is associated with lower age of menopause. Although current societal guidelines do not recommend diagnostic evaluation of menopause in women older than 45 years, our data suggest that there is a risk of misclassifying FHA as menopause in low-weight women if diagnostic evaluation is not performed. Further studies are necessary to determine the role and clinical benefit of diagnostic confirmation of menopause in low-weight women with amenorrhea. Presentation: No date and time listed

LBMON141 Macroorchidism In A Patient With A Functional Gonadotroph Macroadenoma

Abstract Background Functioning gonadotroph adenomas (FGAs) are rare, since most pituitary adenomas of gonadotroph origin are clinically silent or non-functioning. FGAs produce hormones that are adequate to result in clinical syndromes. Clinical case We describe a 38-year-old male who presented with pressure effects from a sellar mass manifesting as persistent and progressive headache. He also complained of swelling of the feet, excessive sweating and coarsening of facial features as well as increased libido. The patient also reported symptoms consistent with obstructive sleep apnoea. His shoe size remained the same and had no features of acromegaly. His visual fields appeared intact on informal assessment. He appeared well virilised and had bilateral macroorchidism, with both testes markedly larger than the largest measurement on the orchidometer (25ml). He was found to have elevated follicle stimulating hormone (FSH) 26.7 to 38.4 IU/L [1.3 -19.3] and testosterone levels from 28.1 to 44.3 nmol/L [6.1 - 27.1] with luteinising hormone (LH) levels being either inappropriately non-suppressed or high, 5.7 - 12.3 IU/L [1.2 - 8.6]. He also had erythrocytosis [Hb 19.5 to 21.7 g/dL (14.3 -18.3) and macroorchidism, owing to high gonadotropin levels. The rest of his pituitary axis appeared intact, including TFT, cortisol levels, and IGF-1, were all within normal limits. Although histology of the pituitary adenoma could not be obtained as the patient declined surgery, clinical and biochemical findings were supportive of FGA diagnosis. Conclusions FGAs are rare, can have none or subtle clinical features, and often present late with mass effects. Functional gonadotroph adenoma should be suspected in a patient with a sellar mass, with high or non-suppressed gonadotropins in the presence of elevated gonadal steroids. Clinical features such as macroorchidism and polycythaemia may be easily missed or misinterpreted. Surgical removal should be the therapy of choice, and if successful can lead to reversal of the biochemical and clinical abnormalities. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Falsely elevated serum estradiol in woman of reproductive age led to unnecessary intervention and delayed fertility opportunity: a case report and literature review

BackgroundThe optimal management of patients in reproductive endocrinology relies on the accuracy and validity of sex hormone assays. Endogenous or exogenous substances can compete with the analyte. This competition can result in interfering errors and falsely indicate elevated serum levels. Obvious interference in estradiol assays appears to occur rarely. Consequently, clinicians who are not familiar with the potential of interference could be misled. In addition to unnecessary investigations and interventions and severe mental stress, falsely elevated estradiol results can result in missed or delayed fertility opportunities.CaseA 28-year-old female with pregnancy demand was diagnosed with polycystic ovary syndrome, Hashimoto’s thyroiditis and subclinical hypothyroidism. She was found to have persistently elevated levels of serum estradiol in the early follicular phase (between 527 and 642 pg/mL). Screening workup was performed for nearly 11 months to find the causes. Serum tumor biomarkers were normal. Abdominal and pelvic computed tomography were negative for adrenal or adnexal masses. A left mesosalpinx cyst and benign pathological results were achieved by laparoscopic surgery. Hormonal substances and dietary supplements were absent, as determined by dietary records. Ultrasound confirmed follicles could grow slowly and eventually ovulate. Falsely elevated estradiol levels were suspected due to the discrepancy among high estradiol levels, follicle growth and normal gonadotropin levels. Immunological interference by heterophile antibody was finally verified by two competitive chemiluminescent immunoassay platforms (estradiol levels in the early follicle phase: 619 pg/mL, Siemens ADVIA CENTAUR and 60 pg/mL, Beckman, DxI 800). Successful clinical pregnancy was eventually achieved by combining induced ovulation, ultrasound monitoring and intercourse guidance.ConclusionsAnalytical interference and laboratory error should be suspicious at first when the clinical characteristics contradict the laboratory results of serum hormones. Measuring serum estradiol with another immunoassay platform is an easy and non-time-consuming method to exclude the heterophile interfering.

Congenital aromatase deficiency – A virilizing masquerade!

Congenital adrenal hyperplasia (CAH) is the most common cause of disorder of sex development in an XX individual. While 21-hydroxylase (CYP21A2) gene mutation is the most common subtype of CAH, aromatase deficiency due to mutations in the gene CYP19A1 is a rare subtype. We report a 46,XX infant with virilized external genitalia, no clinical signs of glucocorticoid or mineralocorticoid deficiency, normal 17-hydroxyprogesterone and adrenocorticotropic hormone, and high levels of gonadotropins and testosterone with inappropriately low estradiol and ovarian cysts. Based on this clinical and biochemical consortium, next-generation sequencing was advised, in which a novel mutation in the gene CYP19A1 was identified.

Lifelong exposure to pyrethroid insecticide cypermethrin at environmentally relevant doses causes primary ovarian insufficiency in female mice

Pyrethroids are a class of widely used insecticides. Our recent epidemiological study of Chinese women reported that pyrethroid exposure was positively associated with the risk of primary ovarian insufficiency (POI). In this study, we utilized cypermethrin (CP), the most frequently detected pyrethroid in the environment, to recognize how lifelong and low-dose exposure to pyrethroids affects ovarian functions and the underlying mechanism(s). Female mice were exposed to CP at doses of human dietary intake of 6.7 μg/kg/day, an acceptable daily intake (ADI) of 20 μg/kg/day, or the chronic reference dose (RfD) of 60 μg/kg/day, starting from gestational day 0.5 until 44-week-old. We assessed effects on fertility, serum hormone levels, ovarian follicular development and ovarian transcriptomic profiles. Chronic exposure to CP at doses of ADI and RfD caused a significant reduction in the size of the primordial follicle pool on postnatal day (PND) 5 and the number of all types of follicles in 44-week-old mice, lower estrogen and higher gonadotropin levels, as well as decreased fertility. Significant increase in apoptosis and decrease in cell proliferation were observed in CP-exposed ovarian follicles from PND 5 and 44-week-old mice. Ovarian transcriptomic data showed that the pro-apoptotic protein BMF and the cell cycle inhibitor p27 were significantly up-regulated in CP-exposed ovaries. Cyp17a1, Cyp19a1 and Hsd17b1 genes involved in the key steps of steroidogenesis were down-regulated in the ovaries of female mice exposed to CP. This study first reported that lifelong exposure to CP at doses of ADI or RfD caused an ovarian phenotype similar to human POI in female mice and provided a mechanistic explanation. Our findings suggest that lifelong exposure to pyrethroids of low doses, which are recommended as ‘safe’ dosages, may have a significant impact on the ovarian health of female mammals and humans.

The impact of metformin on prolactin levels in postmenopausal women

Metformin-induced reduction in prolactin levels is more pronounced in users of hormonal contraception than in non-users. The current study was aimed at investigating whether physiological concentrations of estradiol determine the impact of metformin on lactotrope secretory function. We studied two matched groups of postmenopausal women with elevated prolactin levels. Twenty-three women were on hormone replacement therapy (group 1), while the remaining ones (group 2, n=23) did not use sex hormones. Because of coexistent prediabetes, all individuals received metformin (2.55-3g daily) for the following six months. Circulating levels of total prolactin, monomeric prolactin, thyrotropin, gonadotropins, free thyroid hormones and estradiol were determined at the beginning and at the end of the study. Compared with group 1, group 2 was characterized by higher gonadotropin levels and lower estrogen levels. Although metformin reduced monomeric prolactin levels in both study groups, this effect was more pronounced in group 1 than in group 2. Only in group 1, metformin decreased total prolactin levels, while only in group 2 the drug reduced FSH levels. Metformin treatment did not affect circulating levels of the remaining hormones. The impact of metformin on total and monomeric prolactin levels correlated with baseline prolactin levels and with the degree of improvement in insulin sensitivity. The obtained results indicate that the impact of metformin on lactotrope secretory function is partially determined by the estrogen status of patients.

A Case of Preterm Ovarian Hyperstimulation Syndrome Presenting With Vaginal Bleeding

Abstract Background: Preterm ovarian hyperstimulation syndrome (POHS) is a rare syndrome described in preterm female infants. This is associated with high serum estradiol and gonadotropin levels, multiple follicular ovarian cysts, and edema of the hypogastric, labial and upper leg regions. This usually occurs at 30 to 39 weeks post-conceptional age (PCA). Vaginal bleeding may or may not be present. We present an unusual case of POHS that had a delayed presentation at 5 months of age (45 weeks PCA) with vaginal bleeding. Case presentation: An extremely premature female infant presented with vaginal bleeding at 5 months of age. Workup revealed pubertal gonadotropins indicating ovarian hyperstimulation. She had mild swelling in the hypogastric region. No breast buds were palpable and there was no clitoromegaly. At the time LH (22.2 mu/ml), FSH (8.3 mu/ml), Estradiol (502.2 pg/mL), and Testosterone (111 ng/dL) were all highly elevated. Multiple ovarian follicles were visualized on her pelvic ultrasound, with generous ovarian dimensions: right ovary (3.6 x 1.6 x 1.9 cm, volume 5.7 cc) and left ovary (2.5 x 2.4 x 1.5 cm, volume 4.7 cc). The largest follicle measured 8.8 mm. The uterus was 3.3 x 1.3 x 1.7 cm, with endometrial stripe thickness of 3 mm. There was no endometrial or adnexal mass. Cosyntropin test showed adequate peak cortisol (32.6 mcg/dL). Her newborn screen had been normal. Serial monitoring of her lab work showed a decrease in her gonadotropin and estradiol levels. She had a recurrence of vaginal bleeding about 3 weeks after initial presentation. By 50 weeks PCA the bleeding had resolved and the LH (1.2 mu/ml), FSH (1.5 mu/ml), estradiol (36 pg/ml) had reduced considerably. Complete normalization of LH (1.2 mu/ml), FSH (1.5 mu/ml), E (36 pg/ml), and testosterone (&amp;lt;7 ng/dl) was demonstrated by 55 weeks PCA. Conclusion: POHS has been attributed to the immaturity of the hypothalamic-pituitary-gonadal axis in preterm infants. Vaginal bleeding has been described in one case [1] several weeks after breast enlargement and swelling of clitoral hood, labia majora, hypogastrium and upper legs. In our case the baby presented with vaginal bleeding at 45 weeks that recurred about 3 weeks later and resolved by 50 weeks, with only minimal swelling. This case underlines the need to be aware of this etiology and its varied presentation. [1] Preterm ovarian hyperstimulation syndrome presented with vaginal bleeding: a case report. Altuntas et al. J Pediatr Endocr Met; 273(3-4):355-358.

Phenotypic and biochemical characteristics and molecular basis in 36 Chinese patients with androgen receptor variants

BackgroundAndrogen insensitive syndrome (AIS) is a rare genetic disease resulting from androgen receptor (AR) mutations and one of the causes of 46, XY disorder of sexual development (DSD). This study aimed to describe the clinical features and molecular defects of 36 Chinese patients with AR variants and investigate the functional alterations of novel variants in vitro.Material and methodsSubjects with AR variants were identified from 150 Chinese 46, XY DSD patients using targeted next-generation sequencing. In-silico and functional assays were performed to evaluate the transcriptional activity and nuclear localization of novel AR variants.ResultsEight novel and fifteen reported AR variants were identified. 30.6% (11/36) of patients harbored additional variants other than AR. Mutations in the Arg841 residue were found in 7 unrelated patients. Postpubertal serum gonadotropin levels were significantly elevated in patients with complete AIS (CAIS) compared with those in patients with partial AIS (PAIS) (P < 0.05). All the novel variants initially predicted to be uncertain significance by in-silico analyses were reclassified as likely pathogenic for defective AR transcriptional activity in vitro, except p.L295P, which was found in an atypical patient with oligogenic mutations and reclassified as likely benign. c.368_369 ins T was observed to interfere with nuclear translocation.ConclusionsCompared with PAIS patients, postpubertal CAIS patients had higher gonadotropin levels. Arg841 was disclosed as the location of recurrent mutations in Chinese AIS patients. Functional assays are important for reclassifying the novel AR variants and re-examining the diagnosis of AIS in specific patients with oligogenic mutations, instead of in-silico analysis.

Sonographic Predictors Of Pelvic Organs In Women With Premature Ovarian Failure

Premature menopause is a pathological condition characterized by the cessation of the functional activity of the ovaries in women under the age of 40 and manifested by amenorrhea, high levels of gonadotropins in the blood, infertility and symptoms of estrogen deficiency. POF occurs on average in 1% of women. The exact nature of the disease remains unknown. The basis of this pathology, regardless of the etiological factor, is a decrease in the reserve of primordial follicles, which is unusual for this age period, up to its complete depletion and the formation of the afollicular type of POF. This condition is described as a "multifactorial syndrome" due to chromosomal abnormalities, genetic disorders, fermentopathies, infectious and iatrogenic factors.

Molecular Basis of LH Action on Breast Cancer Cell Migration and Invasion via Kinase and Scaffold Proteins.

Breast cancer (BC) is a major public health problem affecting women worldwide. Approximately 80% of diagnosed cases are hormone-dependent breast cancers. These hormones are known to stimulate tumor development and progression. In this setting, tentative evidence suggests that luteinizing hormone (LH) may also play a role in tumors. In BC cells that express functional LH receptors (LHR), this hormone regulates cell migration and invasion by controlling several kinases that activate actin cytoskeletal proteins. In this article, we show that LH induces phosphorylation of paxillin and its translocation toward the plasmatic membrane, where focal adhesion complexes are assembled. This process is triggered via a rapid extra-gonadal LHR signaling to Src/FAK/paxillin, which results in the phosphorylation/activation of the nucleation promoter factors cortactin and N-WASP. As a consequence, Arp2/3 complexes induce actin polymerization, essential to promote cell adhesion, migration, and invasion, thus enhancing metastatic spread of tumoral cells. Our findings provide relevant information about how gonadotrophins exert their action in BC. This information helps us understand the extragonadal effects of LH on BC metastasis. It may provide new perspectives for therapeutic treatment, especially for women with high serum levels of gonadotrophins.

Hydrocortisone as a Potential Treatment of Savage Ovary Syndrome: A Rare Case from Syria

Advances in Medical, Dental and Health Sciences,2020,3,3,49-51.DOI:10.5530/amdhs.2020.3.12Published:October 2020Type:Case ReportAuthors:Dema Adwan Author(s) affiliations:Dema Adwan* Damascus University Gynecology and Obstetrics Hospital, SYRIA. Abstract:A 32-year old woman with a secondary amenorrhea for 5 years presented to my clinic (April 2019), previously had been treated as a premature ovarian failure patient and put on HRT. With further investigation, FSH Levels were high at the menopausal range, whereas the AMH levels and antral follicles count were within normal ranges and found to be age-compatible, These findings, as well as the failure of ovaries to respond to exogenous gonadotropins, helped to set the diagnosis of Savage Ovary Syndrome, which is also known as Insensitive Ovary Syndrome (IOS). Written informed consent was obtained from the patient for publication of this case report and accompanying images" Patient was convinced to be treated empirically with a high dose of Hydrocortisone and the result was the patient well responded as a normal spontaneous menstruation happened. The analysis of FSH and estradiol induces normal values and the return of the functional activity of the ovary to the formation of multiple ovarian bilateral follicle and give an echo feature similar to the ovarian hyper stimulatory syndrome with an increase the thickness of the endometrium. This case shows the importance of further studying patients with secondary amenorrhea and high levels of gonadotropins and not to treat them all as premature ovary insufficiency patients, just like our patient was firstly treated for a long time. Furthermore, the case highlights the potential benefit of the treatment of Savage Ovary Syndrome patients with Hydrocortisone. Keywords:Antral follicles, Gonadotropin, Infertility, Insensitive ovary, Resistant ovarian syndrome, Secondary amenorrheaView:PDF (535.52 KB)

Managing Ectopic Pregnancies by Targeting Chorionic Villi with a Transvaginal Injection of Ethanol into the Lacunar Space.

Methotrexate has been the main mode of non-surgical treatment for ectopic pregnancies. However, we have developed an easier, repeatable method that can be applied even to patients with a high beta-human chorionic gonadotropin (β-hCG) level and/or positive fetal heartbeat, by targeting chorionic villi with a transvaginal injection of absolute ethanol (AE) into the lacunar space (intervillous space). The efficacy and safety of this method were examined in 242 cases of ectopic pregnancy, including 103 with positive fetal heartbeat. Serum β-hCG level was measured at frequent intervals, and transvaginal ultrasonography was performed to observe the gestational sac and hyperechoic inner ring. Of the 242 patients, 222 (91.7%) were successfully treated. The average number of AE injection(s) required was 1.6 (range: 1–5), and the average dose was 3.2 mL. After the treatment, many of the patients tried to conceive again, and 63 of the traceable 145 patients (43.4%), who had fallopian tube pregnancy, and 7 of the traceable 12 patients (58.3%), who had cervical or cesarean scar pregnancies, successfully conceived and delivered babies with no observed side effects. Therefore, this method could be an effective treatment for ectopic pregnancy with the potential to replace conventional surgical interventions and medical treatment using methotrexate.

Minipuberty of human infancy - A window of opportunity to evaluate hypogonadism and differences of sex development?

Activation of the hypothalamic-pituitary-gonadal (HPG) axis happens in 3 phases during life. The first phase is during fetal life and is only separated from the second phase, called minipuberty, by the high concentration of placental hormones at birth. The third period of activation of the HPG axis is puberty and is well-described. Minipuberty consists of the neonatal activation of the HPG axis, mainly in the first 1–6 months, where the resulting high levels of gonadotropins and sex steroids induce the maturation of sexual organs in both sexes. With gonadal activation, testosterone levels rise in boys with peak levels after 1–3 months, which results in penile and testicular growth. In girls, gonadal activation leads to follicular maturation and a fluctuating increase in estrogen levels, with more controversy regarding the actual influence on the target tissue. The regulation of the HPG axis is complex, involving many biological and environmental factors. Only a few of these have known effects. Many details of this complex interaction of factors remain to be elucidated in order to understand the mechanisms underlying the first postnatal activation of the HPG axis as well as mechanisms shutting down the HPG axis, resulting in the hormonal quiescence observed between minipuberty and puberty. Minipuberty allows for the maturation of sexual organs and forms a platform for future fertility, but the long-term significance is still not absolutely clear. However, it provides a window of opportunity in the early detection of differences of sexual development, offering the possibility of initiating early medical treatment in some cases.

Romantic Love and Reproductive Hormones in Women.

Increased reproductive success is among the most commonly proposed adaptive functions of romantic love. Here, we tested if hormonal changes associated with falling in love may co-vary with hormonal profiles that predict increased fecundity in women. We compared blood serum levels of estradiol (E2, E2/T), luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), free testosterone (fT), and cortisol (CT), measured in the early follicular phase of the menstrual cycle in single women (N = 69) and in women at the beginning of a romantic heterosexual relationship who reported being in love with their partner (N = 47). Participants were healthy, regularly cycling women aged 24 to 33 who did not use hormonal contraception. We found that women in love had higher levels of gonadotropins (FSH, LH) and lower testosterone levels compared to single women who were not in love. These groups of women did not, however, differ in terms of estradiol, prolactin, or cortisol levels.