A rare variant of mullerian agenesis: a case report and review of the literature.

INTRODUCTION: Menstruation is a developmental milestone and usually marks healthy and normal pubertal changes in females. Menarche refers to the onset of first menstruation in a female. The causes of primary amenorrhea include outflow tract abnormalities, resistant endometrium, primary ovarian insufficiency, and disorders of the hypothalamus, pituitary, or other endocrine glands. A rare variant of mullerian agenesis, which warrants an individualized approach to management, is presented here. CASE REPORT: We present here the case of a 25-year-old Indian female with pain in the lower abdomen and primary amenorrhea. After a thorough history, clinical examination, imaging, and diagnostic laparoscopy, two small uteri, a blind upper half vagina, bilateral polycystic ovaries, and a blind transverse connection between the two uteri-a horseshoe band cervix-were detected, which confirmed the diagnosis of mullerian agenesis. There was evidence of adenomyosis in the mullerian duct element. This is a rare form of Müllerian abnormality with an unusual presentation. CONCLUSION: Mullerian agenesis is the most common cause of primary amenorrhea with well-developed secondary sexual characteristics. There are various forms of mullerian agenesis. Most of the cases are managed by a multidisciplinary team. Rare variants warrant an individualized approach to management.

Menstrual characteristics of atypical anorexia nervosa.

OBJECTIVE: While menstrual irregularities are acknowledged in restrictive-type eating disorders (EDs), the menstrual characteristics specific to atypical anorexia nervosa (AAN) remain inadequately defined. This study aims to compare the menstrual features of anorexia nervosa (AN) and AAN. METHOD: Adolescents diagnosed with AN or AAN who exhibited secondary amenorrhoea at presentation and had their menstrual cycles restored during follow-up were eligible for this study. Clinical and menstrual data at admission and during follow-up were obtained from patient files, and compared between the AN and AAN cohorts. RESULTS: The study included a total of 77 patients (38 with AN and 39 with AAN). The extent of weight loss and the disease duration until the onset of amenorrhoea were comparable in the two groups. However, the duration of illness and the time since the last menstrual period at admission were shorter in the AAN group. Moreover, amenorrhoea manifested at a higher body mass index, and the return of menses occurred more rapidly with less weight gain in the AAN group after the onset of clinical follow-up. Additionally, the AAN group exhibited a shorter overall duration of amenorrhoea. CONCLUSIONS: This study highlights the significance of recognising amenorrhoea in restrictive disorders, even when individuals maintain a normal weight. The faster return of menstrual cycles and shorter duration of amenorrhoea observed in adolescents with AAN emphasise the significance of early diagnosis and prompt initiation of treatment. Regardless of the patient's presenting complaint and weight status, obtaining a comprehensive ED history is essential when addressing concerns regarding amenorrhoea or menstrual irregularities.

Associations between low body weight, weight loss, and medical instability in adults with eating disorders.

OBJECTIVE: The physical complications of atypical anorexia nervosa remain understudied, with most studies completed in adolescents. This study seeks to examine the impact of various weight measures as predictors of medical instability in a large cohort of adult eating disorder patients. METHODS: In this retrospective cohort study, the impact of admission body mass index (BMI), weight suppression, and recent weight loss (the rate of weight loss within the last 12 months) toward the development of medical complications of malnutrition were examined. Multivariable logistic regression assessed the association of binary clinical outcomes of interest with recent weight loss and weight suppression (adjusting for age, admission BMI, gender, and purging behaviors). Odds ratios (OR) and 99% confidence intervals were reported. RESULTS: Greater recent weight loss increased the odds of developing low prealbumin and reduced hand grip strength. A greater weight suppression was associated with increased likelihood of amenorrhea, reduced systolic blood pressure, nadir hemoglobin, and weekly weight gain upon nutritional rehabilitation. Lower admission BMI was predictive of all the medical outcomes examined, with the exception of bradycardia, and was generally the strongest predictor based on standardized coefficients. DISCUSSION: Recent weight loss and weight suppression are predictive of some of the physiologic changes of malnutrition, although low BMI is seemingly the greatest predictor for the development of these complications. These findings suggest that some patients with aggressive weight suppression and/or acute weight loss would benefit from medical stabilization, although this needs to be further defined. PUBLIC SIGNIFICANCE: In adults, low BMI seems to be a better predictor of medical complications than weight suppression or aggressive recent weight loss. In adults, greater weight suppression is associated with increased likelihood of amenorrhea, reduced systolic blood pressure, nadir hemoglobin, and weight gain upon nutritional rehabilitation.

Cardiac involvement and its clinical significance in patients with anorexia nervosa.

Cardiac complications are a major concern in patients with anorexia nervosa (AN) which contribute to morbidity and mortality. However, limited information exists regarding risk factors for the development of these complications. Our objective was to investigate the prevalence and associated risk factors of cardiac involvement among children and adolescents with AN admitted to a tertiary pediatric hospital. We collected demographic, clinical, and laboratory data from individuals with AN hospitalized between 2011 and 2020 in Schneider Children's Medical Center in Israel. Diagnosis was based on established criteria (DSM-5). Patients with other co-morbidities were excluded. Cardiac investigations included electrocardiograms (ECG) and echocardiograms. We conducted correlation tests between cardiac findings and clinical and laboratory indicators. A total of 403 AN patients (81.4% were females) with a median age of 15 ± 2 years were included in the study. Sinus bradycardia was the most common abnormality, observed in 155 (38%) participants. Echocardiogram was performed in 170 (42.2%) patients, of whom 37 (22%) demonstrated mild cardiac aberrations. Among those aberrations, 94.6% could be attributed to the current metabolic state, including pericardial effusion (15.3%) and valve dysfunction (8.8%). Systolic or diastolic cardiac dysfunction, tachyarrhythmias, or conduction disorders were not observed. Patients with new echocardiographic aberration had significantly lower body mass index (BMI) at admission, and the prevalence of amenorrhea and hypotension was higher in this group. CONCLUSIONS: The prevalence of cardiac involvement, except for sinus bradycardia, was notably low in our cohort. The presence of cardiac aberrations is correlated with several clinical variables: lower body mass index (BMI) and the presence of amenorrhea and hypotension at admission. Patients presenting with these variables may be at high risk for cardiac findings per echocardiography. Dividing the patients into high and low risk groups may enable targeted evaluation, while avoiding unnecessary cardiac investigations in low-risk patients. WHAT IS KNOWN: • Cardiac involvement in anorexia nervosa (AN) patients is a major concern, which contributes to morbidity and mortality. • It is unknown which patients are prone to develop this complication. WHAT IS NEW: • Cardiac complications in our cohort are less frequent compared to previous studies, and it is correlated with lower body mass index (BMI) at admission, and the prevalence of amenorrhea and hypotension.

Proposal for targeted, neo-evolutionary-oriented, secondary prevention of early-onset endometriosis and adenomyosis. Part I: pathogenic aspects.

The potential for repeated ovulation and menstruation is thought to have provided a Darwinian advantage during the Palaeolithic. Reproductive conditions remained relatively stable until the pre-industrial era, characterized by late menarche, very young age at first birth, multiple pregnancies, and prolonged periods of lactational amenorrhoea. For hundreds of thousands of years, menstruators experienced few ovulatory cycles, even though they were genetically adapted to ovulate and menstruate every month. In the post-industrial era, the age at menarche gradually declined, the age at first birth progressively increased, and breastfeeding became optional and often of short duration. This created a mismatch between genetic adaptation and socio-environmental evolution, so that what was initially a probable reproductive advantage subsequently contributed to increased susceptibility to diseases associated with lifetime oestrogen exposure, such as ovarian, endometrial and breast cancer and, hypothetically, also those associated with the number of ovulatory menstruations, such as endometriosis and adenomyosis. The incidence of endometriosis shows a steep and progressive increase around the age of 25 years, but given the consistently reported delay in diagnosis, the actual incidence curve should be shifted to the left, supporting the possibility that the disease has its roots in adolescence. This raises the question of whether, from an evolutionary point of view, anovulation and amenorrhoea should not still be considered the physiological state, especially in the postmenarchal period. However, an increase in the frequency of endometriosis in recent decades has not been demonstrated, although this deserves further epidemiological investigation. In addition, as endometriosis occurs in a minority of individuals exposed to retrograde menstruation, other important pathogenic factors should be scrutinised. Research should be resumed to explore in more detail the transtubal reflux of not only blood, but also endometrial cells, and whether they are systematically present in the peritoneal fluid after menstruation. If repetitive ovulatory menstruation during the early reproductive years is shown to increase the risk of endometriosis and adenomyosis development and progression in susceptible individuals, hormonal interventions could be used as secondary prevention in symptomatic adolescents.

Longitudinal Assessment of Bone Mineral Density in Women Living With and Without HIV Across Reproductive Phases.

BACKGROUND: Women living with HIV commonly experience low areal bone mineral density (BMD), but whether this is affected by low ovarian hormonal states (prolonged amenorrhea or menopause) is unknown. We compared rates of BMD loss between women living with HIV and HIV-negative control women and investigated its association with low ovarian hormonal states. SETTING: Women living with HIV were enrolled from Vancouver Canada and controls from 9 Canadian sites. METHODS: This longitudinal analysis included age-matched women living with HIV in the Children and Women: AntiRetrovirals and Markers of Aging cohort and controls in the population-based Canadian Multicentre Osteoporosis Study. Rate of change/year in BMD at the total hip and lumbar spine (L1-L4) between 3 and 5 years was compared between groups, adjusting for sociodemographic and clinical variables. RESULTS: Ninety-two women living with HIV (median [interquartile range] age: 49.5 [41.6-54.1] years and body mass index: 24.1 [20.7-30.8] kg/m 2 ) and 278 controls (age: 49.0 [43.0-55.0] years and body mass index: 25.8 [22.9-30.6] kg/m 2 ) were included. Total hip BMD loss was associated with HIV (ß: -0.003 [95% CI: -0.006 to -0.0001] g/cm 2 /yr), menopause (ß: -0.007 [-0.01 to -0.005] g/cm 2 /yr), and smoking (ß: -0.003 [-0.006 to -0.0002] g/cm 2 /yr); BMD gain was linked with higher body mass index (ß: 0.0002 [0.0007-0.0004] g/cm 2 /yr). Menopause was associated with losing L1-L4 BMD (ß: -0.01 [-0.01 to -0.006] g/cm 2 /yr). Amenorrhea was not associated with BMD loss. CONCLUSIONS: HIV and menopause negatively influenced total hip BMD. These data suggest women living with HIV require hip BMD monitoring as they age.

A rare case of Swyer syndrome from Pakistan in a young girl with primary amenorrhea and 46XY genotype.

Swyer syndrome is a condition where individuals with a 46XY karyotype, typically associated with males, display complete gonadal dysgenesis and lack testicular differentiation. This results from a mutation in the SRY gene, which is essential for testis development. As a consequence, affected individuals who appear phenotypically female have male chromosomes but do not develop functional testes. As a result, there is an absence of testosterone that leads to lack of masculinization and the presence of female genitalia. This article describes a 20-year-old female from Pakistan who exhibited primary amenorrhea. On examination, she possessed a typical female physique but lacked breast growth and axillary hair. She had scant pubic hair with female-type external genitalia. The pelvic imaging showed a underdeveloped uterus, along with small ovaries and fallopian tubes. Her karyotype came out to be 46XY. The examination and radiological results indicated Swyer syndrome. During laparoscopy, the patient's uterus was found to be infantile, while the fallopian tubes were healthy. Streak gonads were also present, and due to the risk of gonadoblastoma, they were surgically removed. Hormone replacement therapy was started to induce pubertal development and optimize bone mineral accumulation.

High-sensitivity troponin-T levels and associated health conditions in 3146 women aged 46.

OBJECTIVE: The aim of the study was to investigate are there associations between common female sex-specific health conditions (oligo/amenorrhea, hyperandrogenism, menopause and polycystic ovary syndrome [PCOS]) and high-sensitivity troponin-T (hs-TnT) levels. METHODS: Cross-sectional and longitudinal analyses of a general population-based prospective cohort study were performed. The hs-TnT levels of 3146 women aged 46 were measured using an Elecsys® Troponin T high-sensitivity assay. Median hs-TnT levels and 25 and 75 percentiles of the cases and controls were compared. Also, a logistic regression analysis using a binary outcome - undetectable hs-TnT (< 3.0 ng/L) versus detectable hs-TnT (≥ 3.0 ng/L) - was performed. RESULTS: Women with oligo/amenorrhea at age 31 had significantly higher hs-TnT levels at age 46 than women without oligo/amenorrhea (4.06 [3.59; 4.86] vs 3.98 [3.44; 4.71] ng/L, p = .042). Menopausal women had significantly higher hs-TnT levels than premenopausal women (4.15 [3.54; 4.91] vs 3.95 [3.45; 4.68] ng/L, p = .012) at age 46. Women with PCOS or hyperandrogenism had comparable hs-TnT levels with their controls. In the adjusted logistic regression analysis, oligo/amenorrhea (odds ratio [OR] = 1.52 [0.90-2.57]), hyperandrogenism (OR = 1.20 [0.75-1.92]), PCOS (OR = 1.51 [0.81-2.84]) and menopause (OR = 1.05 [0.63-1.74]) were not significantly associated with detectable hs-TnT. CONCLUSIONS: This study was the first to investigate how oligo/amenorrhea, hyperandrogenism, PCOS and menopause are associated with hs-TnT. Although women with oligo/amenorrhea and menopause had higher hs-TnT levels than women without these conditions, the difference was small. Larger studies are required to better understand the effects of oligo/amenorrhea on cardiovascular health.

No previous studies have investigated the association between common female sex-specific health conditions, such as oligo/amenorrhea, hyperandrogenism and PCOS, and hs-TnT levels. Only one prior study has investigated the association between menopause and hs-TnT levels.Hs-TnT levels were significantly higher in women with oligo/amenorrhea and relatively early menopause at age 46 than women without these conditions, whereas women with hyperandrogenism or PCOS and their controls have comparable hs-TnT levels.The effect of oligo/amenorrhea on cardiovascular health should be further investigated. A simple question about the presence of oligo/amenorrhea might identify women at increased risk of cardiovascular disease.

A prospective longitudinal analysis of the predictors of amenorrhea after breast cancer chemotherapy: Impact of BRCA pathogenic variants.

BACKGROUND: Better tools for post-chemotherapy amenorrhea risk assessment are needed for fertility preservation decision-making. Our aim was to determine the predictors of amenorrhea risk at 12 and 18 months post-chemotherapy in women with breast cancer. METHODS: 142 women with breast cancer were longitudinally followed for their menstrual changes at 6, 12, and 18 months after the completion of adjuvant chemotherapy with an Anthracycline-Cyclophosphamide-based (AC-based) or Cyclophosphamide-Methotrexate +5-Fluorouracil regimen. Pre- and/or post-chemo AMH levels, age, BMI, tamoxifen use, regimen type, and germline BRCA pathogenic variant (gBRCApv) status were evaluated for the prediction of amenorrhea at 6-18 months. RESULTS: In multivariable-adjusted logistic regression, age (p = 0.03) and AMH (p = 0.03) at 12 months, and gBRCApv status (p = 0.03) at 18 months were significant predictors of amenorrhea (areas under the ROC curve of 0.77 and 0.76, for 12 and 18 months, respectively) among 102 evaluable subjects. An undetectable AMH immediately post-chemotherapy was predictive of amenorrhea with <18 month follow-up. In longitudinal analysis estimating time trends, baseline AMH and gBRCApv status was associated with the risk of amenorrhea over 6-18 months; the AMH >2.0 ng/mL group showed attenuated time-trend risk of amenorrhea versus AMH ≤2.0 group (ratio of ORs = 0.91, 95% CI = 0.86-0.97, p = 0.002), while the gBRCApv + showed a steeper time trend, versus the controls (ratio of ORs = 1.12, 95% CI = 1.04-1.20, p = 0.003). CONCLUSIONS: In addition to the pre- and post-treatment AMH levels, gBRCApv status is a novel potential predictor of amenorrhea at 12 and 18 months after chemotherapy. The higher likelihood of amenorrhea in women gBRCApv suggests that they are more prone to losing their fertility post-chemotherapy.

A Perplexing Case of a Germ Cell Tumor: A Case Report.

Germ cell tumors (GCTs) are associated with pure gonadal dysgenesis or Swyer syndrome. Swyer syndrome usually presents with primary amenorrhea, streak ovaries, and mixed GCT. However, our patient presented with secondary amenorrhea, normal female external genitalia, and a mixed GCT. Constitutional karyotype was suggestive of 46,XY. Management comprised chemotherapy, followed by surgery. Histopathology was suggestive of dysgerminoma complicating a gonadoblastoma. The purpose of reporting this case is its rarity and the importance of diagnosing an XY karyotype, as the incidence of GCTs is higher in these patients.

Amenorrhea and oligomenorrhea risk related to exercise training volume and intensity: Findings from 3705 participants recruited via the STRAVA™ exercise application.

OBJECTIVES: To investigate associations between self-reported exercise training habits and amenorrhea/oligomenorrhea among physically active women. DESIGN: A cross-sectional survey was completed by 3705 women (median age = 40 years [quartile 1, quartile 3: 30, 45], body mass index = 22.1 kg/m2 [20.5, 24.2]) representing multiple nationalities and sports via the STRAVA™ exercise application. Respondents selected the amount of time they participated in low intensity, moderate intensity, and high intensity exercise training per week. Amenorrhea/oligomenorrhea was defined as self-reporting ≤10 menses in the last year. METHODS: Associations between weekly exercise volume for low intensity training, moderate intensity training, and high intensity training and amenorrhea/oligomenorrhea were modeled with univariate logistic regression models, followed by adjustment for age and body mass index. RESULTS: Amenorrhea/oligomenorrhea prevalence was 16 % (n = 576/3705), with no difference by country of origin or most sport modes. In adjusted models, participating in low intensity training ≥7 h/week or moderate intensity training ≥6 h/week was associated with 1.43 (95 % confidence interval: 1.04-1.96) and 1.46 (1.10-1.95) greater odds of amenorrhea/oligomenorrhea compared to 2 to 3 h/week, respectively. Similarly, high intensity training ≥5 h/week was associated with 1.41 (1.03-1.92) greater odds of amenorrhea/oligomenorrhea compared to 1 to 2 h/week. Participating in low intensity training for ≤30 min/week compared to 2 to 3 h/week was associated with reduced amenorrhea/oligomenorrhea odds (0.65 [0.44-0.94]). CONCLUSIONS: Taken together, these associations suggest greater weekly exercise volume, irrespective of intensity, may increase amenorrhea/oligomenorrhea risk among physically active women.

Efficacy and safety of vilaprisan in women with uterine fibroids: data from the ASTEROID 3 randomized controlled trial.

OBJECTIVE: Vilaprisan is a highly potent selective progesterone receptor modulator shown to reduce heavy menstrual bleeding, induce amenorrhea, and diminish uterine fibroid volume in phase 2 studies. The objective of ASTEROID 3 was to demonstrate the superiority of vilaprisan compared with placebo in the treatment of heavy menstrual bleeding in women with uterine fibroids. DESIGN: Randomized, double-blind, placebo-controlled, multicenter phase 3 study. SETTING: Hospitals and medical centers. PATIENT(S): Women with ≥1 uterine fibroid of ≥3 cm and heavy menstrual bleeding of >80 mL/cycle. INTERVENTION(S): Women were randomly assigned to 1 of 4 treatment arms, which were planned to comprise 2 treatment periods of 12 weeks, each with vilaprisan (2 mg/d) or placebo that were continuous or separated by a break of one bleed. MAIN OUTCOME MEASURE(S): Amenorrhea (primary end point; <2 mL in the last 28 days of treatment) and heavy menstrual bleeding response (key secondary end point; <80 mL/cycle and >50% reduction in bleeding from baseline) were measured with the alkaline hematin method. Change in volume of the 3 largest fibroids from baseline to end of treatment was assessed by ultrasound. Safety was monitored throughout the study. RESULT(S): Overall, 75 women completed the first 12 weeks of treatment. Statistically significant and clinically meaningful differences were observed between the vilaprisan- and placebo-treated groups in both the full analysis and per-protocol sets. In the per-protocol set (n = 36 and n = 12 for the vilaprisan and placebo groups, respectively), amenorrhea was observed more frequently in women treated with vilaprisan than in those who received placebo (83.3% vs. 0%, P<.0001), with a median time to onset of 3 days in the vilaprisan group. Similarly, more vilaprisan- than placebo-treated women achieved a response in heavy menstrual bleeding (91.7% vs. 25.0%, P<.0001). Serious adverse events were reported for 22 (27.8%) of 79 women and were evenly distributed among the 4 groups receiving vilaprisan and/or placebo. None of these events led to study discontinuation or were related to the liver, and no new safety findings were identified compared with the earlier phase 2 ASTEROID studies. CONCLUSION(S): Vilaprisan is efficacious and well tolerated over 12 weeks in the treatment of heavy menstrual bleeding associated with uterine fibroids. Further investigations of the long-term efficacy and safety of vilaprisan are warranted. CLINICAL TRIAL REGISTRATION NUMBER: NCT03400943 (ClinicalTrials.gov).

Menstrual Function, Eating Disorders, Low Energy Availability, and Musculoskeletal Injuries in British Servicewomen.

PURPOSE: This study aimed to investigate associations between menstrual function, eating disorders, and risk of low energy availability with musculoskeletal injuries in British servicewomen. METHODS: All women younger than 45 yr in the UK Armed Forces were invited to complete a survey about menstrual function, eating behaviors, exercise behaviors, and injury history. RESULTS: A total of 3022 women participated; 2% had a bone stress injury in the last 12 months, 20% had ever had a bone stress injury, 40% had a time-loss musculoskeletal injury in the last 12 months, and 11% were medically downgraded for a musculoskeletal injury. Menstrual disturbances (oligomenorrhea/amenorrhea, history of amenorrhea, and delayed menarche) were not associated with injury. Women at high risk of disordered eating (Female Athlete Screening Tool score >94) were at higher risk of history of a bone stress injury (odds ratio (OR; 95% confidence interval (CI)), 2.29 (1.67-3.14); P < 0.001) and time-loss injury in the last 12 months (OR (95% CI), 1.56 (1.21-2.03); P < 0.001) than women at low risk of disordered eating. Women at high risk of low energy availability (Low Energy Availability in Females Questionnaire score ≥8) were at higher risk of bone stress injury in the last 12 months (OR (95% CI), 3.62 (2.07-6.49); P < 0.001), history of a bone stress injury (OR (95% CI), 2.08 (1.66-2.59); P < 0.001), a time-loss injury in the last 12 months (OR (95% CI), 9.69 (7.90-11.9); P < 0.001), and being medically downgraded with an injury (OR (95% CI), 3.78 (2.84-5.04); P < 0.001) than women at low risk of low energy availability. CONCLUSIONS: Eating disorders and risk of low energy availability provide targets for protecting against musculoskeletal injuries in servicewomen.

Premature ovarian insufficiency and infertility.

BACKGROUND: Premature ovarian insufficiency (POI) is the loss of ovarian function before the age of 40 years and can be spontaneous or iatrogenic. It is an important cause of infertility, and the diagnosis should be considered in any woman presenting with oligo/amenorrhoea, even in the absence of menopausal symptoms suchas hot flushes. OBJECTIVE: The aim of this article is to provide an overview of the diagnosis of POI and its management with respect to infertility. DISCUSSION: Diagnostic criteria for POI are follicle-stimulating hormone levels >25 IU/L on two occasions at least one month apart following 4-6 months of oligo/amenorrhoea, with exclusion of secondary causes of amenorrhoea. Approximately 5% of women will have a spontaneous pregnancy after a POI diagnosis; however, most women with POI will require a donor oocyte/embryo for pregnancy. Some women may elect to adopt or live childfree. Fertility preservation should be considered for those at risk of POI.

A 12-Year-Old Girl with Juvenile Granulosa Cell Tumor of the Ovary, Presenting with Adolescent Hyperprolactinemia, Galactorrhea, and Amenorrhea.

BACKGROUND Juvenile-type granulosa cell tumors (JGCTs) are a rare subtype of sex cord stromal tumor with a characteristic histology that is commonly found in the first 3 decades of life. It most commonly presents with symptoms of hyperestrogenism, which may present as precocious pseudopuberty or as menstruation-related symptoms, allowing for early detection of the tumor. CASE REPORT We present the case of a 12-year-old girl who presented to her primary care provider (PCP) with secondary amenorrhea with intermittent abdominal pain, who underwent an ultrasound for further evaluation, which revealed a large incidental pelvic mass. She was admitted to the Emergency Department (ED) and had findings of galactorrhea and hyperprolactinemia on examination. Imaging studies demonstrated a large ovarian mass measuring 15.0×9.0×18.8 cm that was resected, and subsequent pathology results showed JGCT stage 1A. CONCLUSIONS Prognosis of granulosa cell tumors (GCT) largely depends on its initial size, stage at diagnosis, residual tumors after surgery, and the subtype of GCT. If the patient is of reproductive age, fertility-sparing surgical options must be considered and patients must be regularly monitored for recurrence. JGCTs can present with minimal to no symptoms of precocious puberty in young girls but may present with amenorrhea, which may be considered normal for their developmental age. Although JGCTs are rare, they are important to include in differential diagnoses of younger female patients with abdominal pain, especially if accompanied by hormonal irregularities.

Endocrine Responses to Triptorelin in Healthy Women, Women With Polycystic Ovary Syndrome, and Women With Hypothalamic Amenorrhea.

CONTEXT: Limited data exist regarding whether the endocrine response to the gonadotropin-releasing hormone receptor agonist (GnRHa) triptorelin differs in women with polycystic ovary syndrome (PCOS) compared with healthy women or those with hypothalamic amenorrhea (HA). OBJECTIVE: We compared the gonadotropin response to triptorelin in healthy women, women with PCOS, or those with HA without ovarian stimulation, and in women with or without polycystic ovaries undergoing oocyte donation cycles after ovarian stimulation. METHODS: The change in serum gonadotropin levels was determined in (1) a prospective single-blinded placebo-controlled study to determine the endocrine profile of triptorelin (0.2 mg) or saline-placebo in healthy women, women with PCOS, and those with HA, without ovarian stimulation; and (2) a retrospective analysis from a dose-finding randomized controlled trial of triptorelin (0.2-0.4 mg) in oocyte donation cycles after ovarian stimulation. RESULTS: In Study 1, triptorelin induced an increase in serum luteinizing hormone (LH) of similar amplitude in all women (mean peak LH: healthy, 52.3; PCOS, 46.2; HA, 41.3 IU/L). The AUC of change in serum follicle-stimulating hormone (FSH) was attenuated in women with PCOS compared with healthy women and women with HA (median AUC of change in serum FSH: PCOS, 127.2; healthy, 253.8; HA, 326.7 IU.h/L; P = 0.0005). In Study 2, FSH levels 4 hours after triptorelin were reduced in women with at least one polycystic morphology ovary (n = 60) vs normal morphology ovaries (n = 91) (34.0 vs 42.3 IU/L; P = 0.0003). Serum anti-Müllerian hormone (AMH) was negatively associated with the increase in FSH after triptorelin, both with and without ovarian stimulation. CONCLUSION: FSH response to triptorelin was attenuated in women with polycystic ovaries, both with and without ovarian stimulation, and was negatively related to AMH levels.

Investigation of the female infertility risk associated with anti-cancer therapy.

Female infertility is a significant health issue worldwide with a rising incidence. Anti-cancer therapy is one of the most important reasons for increasing infertility. Although anti-cancer treatment increases the rate of survival, it decreases the quality of life through its side effects. The most substantial side effects are sexual dysfunction and infertility. Breast cancer is the most common cancer. The first-line treatment of breast cancer is chemotherapy by alkylating agents like cyclophosphamide, which leads to infertility. For instance, persistent chemotherapy-induced amenorrhea among breast cancer patients could affect almost half of the patients that undergo such therapy. However, some agents or therapeutic methods can ameliorate these intoxicating effects. Chemotherapy plus gonadotropin-releasing hormone agonist, in breast cancer patients, can not only improve overall survival but also reduce ovarian toxicity. Age plays an essential role in chemotherapy-induced amenorrhea. Chemotherapy at a younger age can reduce the risk of infertility. Gynecological cancers including uterine and ovarian cancer, which have high mortality rates, are the most related cancers to infertility. Surgery is the primary treatment of gynecological cancers. Studies demonstrated that fertility-sparing surgery is a better option than radical surgery. In addition, neoadjuvant chemotherapy is mostly a better option than primary cytoreductive surgery in terms of survival and fertility. Immune checkpoint inhibitors (ICIs) have recently played a major role in treating various cancer types. However, ICIs are associated with hypophysitis, which affects ovaries and can lead to infertility. There are some options for ovarian preservation such as embryo cryopreservation, oocyte cryopreservation, ovarian transposition, ovarian tissue cryopreservation, and ovarian suppression by GnRH agonists. Anti-müllerian hormone level can be utilized to monitor the ovarian reserve. Moreover, to avoid fertility loss, approaches such as using transplantation of human placenta mesenchymal stem cells, administrating anti-inflammatory agents and hormone therapy are under investigation.

Rare virilizing tumor: ovarian steroid cell tumor, not otherwise specified: a case report.

BACKGROUND: Ovarian steroid cell tumors, not otherwise specified is a rare sex cord-stromal tumor. Almost 60% of all steroid cell tumors are categorized as not otherwise specified and represent less than 0.1% of all ovarian neoplasm. Some of them are endocrinologically active, producing virilization signs in young women. The recommended treatment is primarily surgical. CASE PRESENTATION: We present the case of a 20-year-old Mexican woman with secondary amenorrhea and virilization signs. She was treated with combined oral contraceptives from 13 years old, due to a misdiagnosis of polycystic ovarian syndrome. However, 4 months after stopping medication, amenorrhea and virilization signs worsened. Biochemically, she had high serum total testosterone and free testosterone levels, and a pelvic and transvaginal ultrasound followed by a pelvic tomography scan demonstrated a right adnexal tumor. She underwent right salpingo-oophorectomy and the histopathological and immunochemistry exams confirmed the diagnosis. The patient was followed for a year after surgery and until then, her menses were regular and she had no recurrence of virilization signs. CONCLUSION: The purpose of this case report is to alert physicians to rule out ovarian steroid cell tumor, not otherwise specified diagnosis in young women with increased testosterone after discarding common causes such as polycystic ovarian syndrome. A multidisciplinary team including a gynecologist, endocrinologist, radiologist, and pathologist should be involved for correct diagnosis at the proper time.

Clinical analysis of high-intensity focused ultrasound (HIFU) combined with hysteroscopy-guided suction curettage (HGSC) in patients with cervical pregnancy.

OBJECTIVE: To evaluate the effectiveness of high-intensity focused ultrasound (HIFU) combined with hysteroscopy-guided suction curettage (HGSC) in treating cervical pregnancy. MATERIALS AND METHODS: This is a retrospective study. Seven patients with cervical pregnancy who visited the Third Xiangya Hospital of Central South University from January 2015 to December 2020 were enrolled in the current study. All seven patients were treated with HIFU under conscious sedation. All of them underwent HGSC at an average of 2 ± 1 days (range: 1-3 days) after HIFU. Before the therapy, the patient's clinical characteristics were collected, including duration of amenorrhea, gravidity and parity, the patient history of cesarean section and miscarriage, and the size of the gestational sac. The levels of ß-hCG and hemoglobin in serum were also reviewed. To assess the clinical outcomes of this combined treatment, the suction time of HGSC, bleeding volume, the clearance time of ß-hCG, and the time with returning of menstruation were evaluated. RESULTS: All seven patients (average age: 31 ± 6 years) have experienced amenorrhea (duration range, 48 ± 8 days) before the treatment of HIFU. The average number of pregnancies was four, and the number of deliveries was one. Previous medical history showed six patients had cesarean sections, and five patients have been miscarriages. After HIFU treatment, the fetal heartbeats were stopped in all seven patients based on the diagnosis by doppler ultrasound. The bleeding of gestational tissue decreased significantly. All patients had only mild lower abdominal pain, no fever, intestinal damage, or other complications were reported. The average operation time of operative suction curettage was 21 ± 9 min (range: 9-32 min), and the median bleeding volume was 10 ± 8 mL (range: 2-20 mL). Follow-up observations showed that the menstruations were returned in patients at an average of 38 ± 9 days (range: 30-50 days) after the treatment. The ß-hCG decreased from 41773 ± 32242 mIU/mL to 13101 ± 8454 mIU/mL in 29 ± 10 days after surgery. CONCLUSION: Based on these results with small subjects, we concluded that HIFU combined with HGSC might be an effective and safe treatment for patients with cervical pregnancy.