Bariatric surgery for spontaneous ovulation in women living with polycystic ovary syndrome: the BAMBINI multicentre, open-label, randomised controlled trial.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. Obesity exacerbates the reproductive complications of PCOS; however, the management of obesity in women with PCOS remains a large unmet clinical need. Observational studies have indicated that bariatric surgery could improve the rates of ovulatory cycles and prospects of fertility; however, the efficacy of surgery on ovulation rates has not yet been compared with behavioural modifications and medical therapy in a randomised trial. The aim of this study was to compare the safety and efficacy of bariatric surgery versus medical care on ovulation rates in women with PCOS, obesity, and oligomenorrhoea or amenorrhoea. METHODS: In this multicentre, open-label, randomised controlled trial, 80 women older than 18 years, with a diagnosis of PCOS based on the 2018 international evidence-based guidelines for assessing and managing PCOS, and a BMI of 35 kg/m2 or higher, were recruited from two specialist obesity management centres and via social media. Participants were randomly assigned at a 1:1 ratio to either vertical sleeve gastrectomy or behavioural interventions and medical therapy using a computer-generated random sequence (PLAN procedure in SAS) by an independent researcher not involved with any other aspect of the clinical trial. The median age of the entire cohort was 31 years and 79% of participants were White. The primary outcome was the number of biochemically confirmed ovulatory events over 52 weeks, and was assessed using weekly serum progesterone measurements. The primary endpoint included the intention-to-treat population and safety analyses were per-protocol population. This study is registered with the ISRCTN registry (ISRCTN16668711). FINDINGS: Participants were recruited from Feb 20, 2020 to Feb 1, 2021. 40 participants were assigned to each group and there were seven dropouts in the medical group and ten dropouts in the surgical group. The median number of ovulations was 6 (IQR 3·5-10·0) in the surgical group and 2 (0·0-4·0) in the medical group. Women in the surgical group had 2.5 times more spontaneous ovulations compared with the medical group (incidence rate ratio 2·5 [95% CI 1·5-4·2], p<0·0007). There were more complications in the surgical group than the medical group, although without long-term sequelae. There were 24 (66·7%) adverse events in the surgical group and 12 (30·0%) in the medical group. There were no treatment-related deaths. INTERPRETATION: Bariatric surgery was more effective than medical care for the induction of spontaneous ovulation in women with PCOS, obesity, and oligomenorrhoea or amenorrhoea. Bariatric surgery could, therefore, enhance the prospects of spontaneous fertility in this group of women. FUNDING: The Jon Moulton Charity Trust.

Deficits in volumetric bone mineral density, bone microarchitecture, and estimated bone strength in women with atypical anorexia nervosa compared to healthy controls.

OBJECTIVE: Anorexia nervosa is associated with low bone mineral density (BMD) and deficits in bone microarchitecture and strength. Low BMD is common in atypical anorexia nervosa, in which criteria for anorexia nervosa are met except for low weight. We investigated whether women with atypical anorexia nervosa have deficits in bone microarchitecture and estimated strength at the peripheral skeleton. METHOD: Measures of BMD and microarchitecture were obtained in 28 women with atypical anorexia nervosa and 27 controls, aged 21-46 years. RESULTS: Mean tibial volumetric BMD, cortical thickness, and failure load were lower, and radial trabecular number and separation impaired, in atypical anorexia nervosa versus controls (p < .05). Adjusting for weight, deficits in tibial cortical bone variables persisted (p < .05). Women with atypical anorexia nervosa and amenorrhea had lower volumetric BMD and deficits in microarchitecture and failure load versus those with eumenorrhea and controls. Those with a history of overweight/obesity or fracture had deficits in bone microarchitecture versus controls. Tibial deficits were particularly marked. Less lean mass and longer disease duration were associated with deficits in high-resolution peripheral quantitative computed tomography (HR-pQCT) variables in atypical anorexia nervosa. DISCUSSION: Women with atypical anorexia nervosa have lower volumetric BMD and deficits in bone microarchitecture and strength at the peripheral skeleton versus controls, independent of weight, and particularly at the tibia. Women with atypical anorexia nervosa and amenorrhea, less lean mass, longer disease duration, history of overweight/obesity, or fracture history may be at higher risk. This is salient as deficits in HR-pQCT variables are associated with increased fracture risk. PUBLIC SIGNIFICANCE: Atypical anorexia nervosa is a psychiatric disorder in which psychological criteria for anorexia nervosa are met despite weight being in the normal range. We demonstrate that despite weight in the normal range, women with atypical anorexia nervosa have impaired bone density, structure, and strength compared to healthy controls. Whether this translates to an increased risk of incident fracture in this population requires further investigation.

Prevalence and risk factors associated with low bone mineral density in Asian adolescents with anorexia nervosa and atypical anorexia nervosa.

OBJECTIVE: This retrospective study aimed to evaluate the prevalence and risk factors for low bone mineral density (BMD) at diagnosis in Asian adolescent females with anorexia nervosa (AN) and atypical AN. METHOD: We analyzed the BMD results for 213 patients between 10 and 18 years of age, with AN and atypical AN receiving care at a pediatric hospital in Singapore. We used linear regression analyses to determine if type of eating disorder, premorbid weight, and duration of amenorrhea were risk factors for low BMD. For a subset of patients with repeat BMD evaluation, we used paired t-tests to assess the impact of weight or menstrual restoration on the change in BMD. RESULTS: The prevalence of BMD height-for-age Z-scores <-2 at presentation was higher in patients with AN (13.0%) than atypical AN (2.3%) (p = .034). In multivariate regression, a diagnosis of atypical AN was protective against low BMD at the lumbar spine (B = 0.394, p = .009) and total body less head (B = 0.774, p = .010). Duration of amenorrhea was not associated with BMD across all sites. For those with repeat BMD measures, there was significantly less deterioration in the BMD Z-scores for patients with weight or menstrual restoration (R = -0.22 ± 0.59, NR = -0.69 ± 0.43, p = .029). CONCLUSIONS: Duration of amenorrhea was not associated with BMD in this sample. A diagnosis of AN was correlated with lower BMD than atypical AN. Further research is needed to better understand the relationship between amenorrhea, weight status, and bone health in Asian adolescents with eating disorders. PUBLIC SIGNIFICANCE: In this sample, 13% of Asian adolescents with AN and 2.3% of Asian adolescents with atypical AN have low BMD. In our study population, duration of amenorrhea was not correlated with BMD. Among adolescents with AN, a history of being underweight at the highest pre-morbid BMI, is correlated with low BMD. It is important for physicians to take a thorough weight history in evaluating bone health in this population.

Chorioretinal biomarkers in hypothalamic amenorrhea.

PURPOSE: The aim of our study was to evaluate changes in the retinal and choriocapillaris circulations in patients with hypothalamic amenorrhea. METHODS: Prospective, cross-sectional observational study on 25 patients (50 eyes) diagnosed with hypothalamic amenorrhea and 25 age-matched healthy women. Optical coherence tomography angiography (OCTA) was used to evaluate the vessel density (VD) of superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris VD layers in whole 6.4 × 6.4-mm image and in fovea grid-based image. In patients' group, systemic parameters were collected: body mass index (BMI), endometrial rhyme thickness, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, insulin, and cortisol. RESULTS: SCP and DCP did not show any statistical difference when comparing patients and controls (all p > 0.05). Differently, choriocapillaris VD in the whole region showed a non-significant tendency toward higher values in the patients group in both eyes (p = 0.038 for right eye [RE], p = 0.044 for left eye [LE]). Foveal choriocapillaris VD was higher in hypothalamic amenorrhea women vs. healthy controls (66.0 ± 2.4 vs. 63.7 ± 6.6%, p = 0.136 for RE; 65.0 ± 2.4 vs. 61.6 ± 7.0%, p = 0.005 for LE). Focusing on correlation with systemic parameters, SCP and DCP foveal density had a medium/high effect size with endometrial rhyme, along with DCP in the fovea area vs. cortisol and SCP in the whole area vs. FSH. CONCLUSION: When comparing hypothalamic amenorrhea patients to healthy subjects, OCTA detected changes in the choriocapillaris layer, showing increased VD in the early stage of the systemic pathology, suggesting that microvascular "compaction" could be a first phase of hypoestrogenism adaptation.

Prolactin levels in functional hypothalamic amenorrhea: a retrospective case-control study.

PURPOSE: Functional hypothalamic amenorrhea (FHA) is due to hypothalamic dysregulation. Literature lacks data about prolactin in FHA women, although both prolactin levels and FHA are associated with stress. Moreover, polycystic ovarian morphology is common in FHA and there is an association between FHA and polycystic ovary syndrome. Thus, the aim of this study was to assess prolactin levels in FHA patients and controls with a special focus on factors influencing prolactin levels, that could be considered as "sensors" of the hypothalamic-pituitary dysregulation. METHODS: In a retrospective cohort study, 140 women with clearly defined FHA were compared to 70 healthy, normally ovulating women matched for age. The main outcome parameter was prolactin. Factors associated with prolactin levels > 12 µg/L were tested using a multivariable binary logistic regression model. RESULTS: The median prolactin level was 11.5 µg/L (interquartile range, IQR 7.5-14.4), which was similar to the control group (median 10.7, IQR 8.3-14.5; p = 0.065). Only two women had hyperprolactinemia (prolactin > 25 µg/L; 1.4%). In a multivariable binary logistic regression model eating disorder (odds ratio, OR 0.206; p = 0.040), excessive exercise (OR 0.280; p = 0.031) and TSH (OR 1.923; p = 0.020) were significantly associated with prolactin levels > 12 µg/L. CONCLUSION: Women with FHA have similar prolactin levels to healthy age-matched individuals. Eating disorders and excessive exercise where associated with prolactin levels < 12 µg/L, in contrast to TSH.

Sexual functioning in women with functional hypothalamic amenorrhea: exploring the relevance of an underlying polycystic ovary syndrome (PCOS)-phenotype.

PURPOSE: To study sexual function and distress in women with functional hypothalamic amenorrhea (FHA) compared to women with FHA and an underlying polycystic ovary syndrome (PCOS)-phenotype, considering also their psychometric variables. As a secondary aim, we explored the relationship between sexual functioning and hormonal milieu in these women. METHODS: This is a retrospective cross-sectional study conducted on 36 women with typical FHA and 43 women with FHA + PCOS-phenotype. The following validated psychometric questionnaires were administered: Female Sexual Functional Index (FSFI), Female Sexual Distress Scale-Revised (FSDS-R), Body Attitude Test (BAT), Bulimia Investigation Test (BITE), State Anxiety Inventory (STAI), Beck Depression Inventory (BDI), Multidimensional Perfectionism Scale (MPS). Available hormones to formulate FHA diagnosis in the standard routine were considered. RESULTS: Women with typical FHA reported a significantly lower FSFI total score than women with FHA + PCOS-phenotype (95% CI for median 16-21.3 vs. 21.1-24.1, p = 0.002), whereas the FSDS-R score was similar in the two groups (95% CI for median 6-16 vs. 6-16.3). No statistically significant differences were evident in body attitude, state and trait anxiety, depression, bulimic risk, and perfectionism between the two groups, confirming the two FHA groups were superimposable from a psychometric perspective. State anxiety correlated negatively with the FSFI total score in both typical FHA (rho: - 0.33, p = 0.05) and FHA + PCOS-phenotype (rho: - 0.40, p = 0.009). In the entire study population, a positive correlation was found between luteinizing hormone, androstenedione, and 17ß-estradiol and the total FSFI score (rho: 0.28, p = 0.01; rho: 0.27, p = 0.01, rho: 0.27, p = 0.01, respectively). CONCLUSION: Women with FHA showed a very high rate of sexual symptoms as part of their condition, but those with a typical diagnosis displayed a more severe sexual impairment as compared with the FHA + PCOS-phenotype, in spite of a similar psychometric profile. Sexual distress was equally present in both groups (approximately 4 out of 10 women). Further studies should be designed to investigate the potential role of sex hormones, mainly LH-driven androstenedione, in influencing women's sexual functioning.

Laparoscopic cervico-isthmic anastomosis for old traumatic disjunction between the cervix and the uterine corpus: a case report and literature review.

BACKGROUND: Old traumatic disjunction between the cervix and the uterine corpus is very rare case. In most cases, it is not immediately noticed until the onset of other symptoms, such as amenorrhea, periodic abdominal pain and so on. Scanty cases of anastomosis surgery via laparoscope have been reported. CASE PRESENTATION: We report here a 23-year-old young woman with the primary amenorrhea due to traumatic cervico-isthmic disjunction. The patient had a closed pelvic fracture at the age of 4 and has experienced periodic lower abdominal pain since the age of 17 years. A complete disjunction between the cervix and the uterine corpus was diagnosed. Laparoscopic cervico-isthmic anastomosis was performed to restore the continuity of the endometrial cavity and cervical canal. After this surgery, normal menstruation was resumed without cyclic abdominal pain. CONCLUSION: Laparoscopic cervico-isthmic anastomosis could reconstruct the uterine outflow tract successfully, alleviate symptoms, and achieve a good short-term outcome.

Decreased neurokinin B as a risk factor of functional hypothalamic amenorrhea.

BACKGROUND: Neurokinin B (NKB) belongs to the tachykinin family of proteins who's regulation is essential for proper function of the reproductive system. It has been shown that patients with functional hypothalamic amenorrhea (FHA) exhibit decreased levels of serum kisspeptin. As kisspeptin secretion is regulated by NKB signaling, it is reasonable to suspect that patients with FHA will also have abnormal NKB secretion. AIM: To assess NKB levels in patients with FHA and to determine whether NKB signaling is affected in these patients. We hypothesized that decreased NKB signaling is a factor contributing to the development of the FHA. MATERIALS AND METHODS: A total of 147 patients with FHA and 88 healthy age-matched controls were enrolled. Baseline blood samples were drawn from both groups to measure serum concentrations of NKB, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), prolactin (PRL), thyroid-stimulating hormone (TSH), free thyroxine (fT4), cortisol, dehydroepiandrosterone sulfate (DHEA-S), testosterone (T), glucose, and insulin. RESULTS: Mean serum NKB levels were found to be decreased significantly in the FHA group when compared with the control group (628.35 ± 324.92 vs. 721.41 ± 337.57 ng/L, respectively p = 0.002). No statistical difference was observed in NKB-1 levels within the FHA group when selecting for normal and decreased body mass index. CONCLUSIONS: Patients with FHA were found to have decreased serum NKB concentrations when compared to healthy controls. Abnormal NKB secretion is likely a key factor contributing to development of FHA.

Impact of combined endometrial resection or ablation and levonorgestrel intrauterine device on postoperative bleeding pattern.

PURPOSE: The aim of this study was to describe the rate of amenorrhea in women treated with transcervical endometrial resection (TCER) or radiofrequency endometrial ablation combined with levonorgestrel intrauterine contraceptive device (LNG-IUD) six months post-operatively. METHODS: The study was performed as a prospective cohort study. All patients were included at four gynecological centers in Region of Southern Denmark. In total, 162 women referred due to menorrhagia, metrorrhagia or menometrorrhagia and offered TCER or radiofrequency endometrial ablation in combination with or without LNG-IUD included during November 2018 to June 2021 at the women's own discretion and without any cost (covered by the hospital). Data were analyzed using a multivariate regression model. RESULTS: In total, 58 women were offered TCER and 31 (53.4%) combined treatment with TCER + LNG-IUD. Among 104 women who received radiofrequency endometrial ablation, 46 (44.2%) underwent combined treatment with LNG-IUD. The incidence of amenorrhea was 26% among women who underwent treatment with TCRE and 52% when treated with TCER + LNG-IUD (adjusted OR 5.16; 95% CI 1.35-19.6; P < 0.016). Radiofrequency endometrial ablation was followed by a 41% incidence of amenorrhea, and when radiofrequency endometrial ablation was combined with LNG-IUD, the incidence of amenorrhea was 63% (adjusted OR 2.15; 95% CI 0.86-5.37; P < 0.1). We observed no statistically significant differences when comparing the groups across. CONCLUSION: Our study suggests that the combination of TCER or radiofrequency endometrial ablation with LNG-IUD was superior to TCER. However, the combined treatment of radiofrequency endometrial ablation with LNG-IUD did not reach statistical significance. Further studies are needed to evaluate the effects of different ablation techniques on the amenorrhea rate.

Mayer-Rokitansky-Kuster-Hauser syndrome in a young female: diagnosis and treatment: a case report.

Mayer-Rokitansky-Kuster-Hauser Syndrome is a rare condition in which Müllerian system does not develop and ends up with rudimentary upper vagina and the uterus. As compared to normal physiology of the ovaries and puberty, the patients present with primary amenorrhoea a key clinical symptom. However, the exact aetiology of the disease is still unknown. A few reports considered environmental and epigenetic changes, hormonal imbalance, and cellular receptor abnormalities as possible risk factors associated with the disease. This case was reported at the Department of Family Medicine, The Indus Hospital, Karachi. A 24-year-old woman, married for eight months, presented with primary amenorrhoea and painful intercourse. Upon detailed clinical evaluation and relevant radiological and diagnostic investigation, an assessment, of Mayer-Rokitansky syndrome was made.

The care of patients with secondary hypothalamic amenorrhoea.

Secondary hypothalamic amenorrhoea is a common menstrual disorder affecting women of reproductive age. In some cases, periods become absent due to prolonged stress on the body, caused by undereating, overexercising and psychological stress. Secondary hypothalamic amenorrhoea is often underdiagnosed and undertreated, and patients may be prescribed oral contraception, which can mask the problem. This article will mainly focus on lifestyle factors associated with this condition and its association with disordered eating.

MENSTRUAL DISORDER IN ADOLESCENTS DURING WAR.

OBJECTIVE: The aim: To investigate the peculiarities of menstrual cycle disorders in teenagers against the background of excessive stress in order to develop a scientifically based set of measures for their correction. PATIENTS AND METHODS: Materials and methods: 120 girls aged 9-18 who were in the war zone or became forced migrants were examined. Examination methods included anamnesis collection, assessment of psycho-emotional state, anthropometry, laboratory and instrumental studies. RESULTS: Results: It was found that the frequency of menstrual cycle disorders in the subjects was 65.8% (n = 79). Among menstrual cycle disorders: dysmenorrhea - 45.6% (n = 36), excessive menstruation - 27.8% (n = 22), secondary amenorrhea - 26.6% (n = 21). 71.7% (n = 86) of the examinees noted a change in eating behavior over the past few months. Almost half of these children had dyshormonal disorders or met the criteria of metabolic syndrome - 45.3% (n = 39). CONCLUSION: Conclusion: Timely detection and adequate correction of psycho-emotional and metabolic disorders in adolescent girls in stressful conditions contributes to the prevention of disorders of menstrual and reproductive function.

Amenorrhea, premenstrual tension syndrome, and dysmenorrhea among women of reproductive age on hemodialysis: A national study in Egypt.

BACKGROUND AND AIM: The current literature concerning the reproductive health of end stage renal disease (ESRD) females is scarce, outdated, and largely unknown in women living in developing countries. This study aims to estimate the prevalence of menstrual abnormalities and their associated factors among ESRD women in reproductive age undergoing chronic hemodialysis (HD) in Egypt. METHODS: Thirty-five dialysis centers were selected by simple random sampling to represent the different regions of Egypt. Non-pregnant women in the reproductive age (15-50 years) receiving dialysis at the participating centers completed a questionnaire about their menstrual health during a routine hemodialysis session. Their responses were verified by reviewing the medical records and assessing their clinical data. RESULTS: Out of the 472 women, 32.6% had amenorrhea. Menstrual irregularities were reported in 37% of the menstruating women. Premenstrual tension syndrome (PMS) was reported in 70% while dysmenorrhea in 58%. Amenorrhea was more prevalent in non-working women who started hemodialysis after the age of 30. PMS was more encountered in women with hypertension or in those with obstructive uropathy or autoimmune disease as a cause of ESRD. Dysmenorrhea was more prevalent among patients with autoimmune disease or chronic hepatitis C virus and those who started dialysis after the age of 30. CONCLUSION: Secondary amenorrhea, dysmenorrhea, and PMS are common among premenopausal women with ESRD on dialysis. Several factors including socio-economic factors, cause of ESRD, and hypertension contribute to these disorders. Future studies are needed to understand the underlying pathophysiologic mechanisms and management of these abnormalities.

Menstrual changes after spinal cord injury.

STUDY DESIGN: This was a single-centre, prospective, descriptive, hospital-based study in females with spinal cord injuries (SCI). OBJECTIVES: To study menstrual changes after SCI. SETTING: The in-patient and out-patient services of the Department of Physical Medicine and Rehabilitation of a tertiary care institute in India between October 2018 and October 2020. METHODS: SCI females who were included in the study answered a questionnaire regarding amenorrhea after injury, menstrual cycle regularity, frequency, duration, flow, dysmenorrhoea and presence of autonomic dysreflexia during menstruation. All the study related data was analysed using SPSS version 24. A p value < 0.05 was considered as statistically significant. RESULTS: 40 females were included. 31 (77.5%) had amenorrhea. The mean duration of return of menstruation was 2.65 months. There was significant reduction in the duration of menstrual flow (p value < 0.001), amount of flow (p value = 0.041) and dysmenorrhea (p value < 0.001) after SCI. CONCLUSIONS: Amenorrhea was seen in 77.5% females. Most of them resumed their menstrual cycle. The menstruation duration and flow were reduced significantly. There is a need to address concerns and reassure females regarding resumption of menstruation after SCI.

Etiology and Secular Trends in Primary Amenorrhea in 856 Patients: A 17-Year Retrospective Multicenter Study in Korea.

BACKGROUND: This study was performed to evaluate etiologies and secular trends in primary amenorrhea in South Korea. METHODS: This retrospective multi-center study analyzed 856 women who were diagnosed with primary amenorrhea between 2000 and 2016. Clinical characteristics were compared according to categories of amenorrhea (hypergonadotropic/hypogonadotropic hypogonadism, eugonadism, disorders of sex development) or specific causes of primary amenorrhea. In addition, we assessed secular trends of etiology and developmental status based on the year of diagnosis. RESULTS: The most frequent etiology was eugonadism (39.8%). Among specific causes, Müllerian agenesis was most common (26.2%), followed by gonadal dysgenesis (22.4%). Women with hypergonadotropic hypogonadism were more likely to have lower height and weight, compared to other categories. In addition, the proportion of cases with iatrogenic or unknown causes increased significantly in hypergonadotropic hypogonadism category, but overall, no significant secular trends were detected according to etiology. The proportion of anovulation including polycystic ovarian syndrome increased with time, but the change did not reach statistical significance. CONCLUSION: The results of this study provide useful clinical insight on the etiology and secular trends of primary amenorrhea. Further large-scale, prospective studies are necessary.

High levels of physical activity in female adolescents with anorexia nervosa: medical and psychopathological correlates.

PURPOSE: While overexercise is commonly described in patients who experience anorexia nervosa (AN), it represents a condition still underestimated, especially in the paediatric population. METHOD: The present study aims at assessing the possible associations between levels of physical activity (PA) and clinical features, endocrinological data and psychopathological traits in a sample of 244 female adolescents hospitalised for AN subdivided into two groups according to PA levels (high PA vs. no/low PA). The two groups were compared through multivariate analyses, while multiple regression analysis was conducted to determine whether physical activity predict specific outcomes. RESULTS: No significant differences were found between the two groups in terms of last Body Mass Index (BMI) before illness, BMI at admission and disease duration, while a difference emerged in delta BMI(rapidity of weight loss), significantly higher in high-PA group (p = 0.021). Significant differences were observed in Free triiodothyronine- (p < 0.001), Free thyroxine (p = 0.046), Follicle-stimulating hormone (p = 0.019), Luteinising hormone (p = 0.002) levels, with values remarkably lower in high-PA group. Concerning psychopathological scales, the high-PA group showed worst Children's Global Assessment Scale (CGAS) scores (p = 0.035). Regression analyses revealed that higher PA predicts higher delta BMI (p = 0.021), presence of amenorrhea (p = 0.003), lower heart rate (p = 0.012), lower thyroid (Free triiodothyronine p < 0.001, Free thyroxine p = 0.029) and gynaecological hormones' levels (Follicle-stimulating hormone p = 0.023, Luteinising hormone p = 0.003, 17-Beta estradiol p = 0.041). Concerning psychiatric measures, HPA predicts worst scores at CGAS (p = 0.019), and at scales for evaluation of alexithymia (p = 0.028) and depression (p = 0.004). CONCLUSIONS: Results suggest that high levels of physical activity in acute AN associate with worst clinical conditions at admission, especially in terms of endocrinological and medical features. LEVEL OF EVIDENCE: Level III.

A case of isolated hypothalamitis with a literature review and a comparison with autoimmune hypophysitis.

Idiopathic hypothalamitis is a rare condition that can cause anterior pituitary dysfunction and central diabetes insipidus (CDI), occasionally accompanied by a disturbance of autonomic regulation known as hypothalamic syndrome. This condition has been described as a subtype of autoimmune (lymphocytic) hypophysitis; however, some cases of isolated hypothalamic involvement with no inflammatory lesions in either the pituitary gland or infundibulum have been reported. The detailed epidemiology and pathophysiology of isolated hypothalamitis have not been clarified. We herein report a case of a solitary hypothalamic lesion in a young woman who showed spontaneous development of CDI and panhypopituitarism accompanied by hyperphagia. The hypothalamic lesion increased from 11 × 7 to 17 × 7 mm over 16 months based on the sagittal slices of magnetic resonance imaging examinations. The negative results for anti-pituitary antibodies and anti-Rabphilin-3A antibodies suggested that upward extension of lymphocytic adenohypophysitis or infundibulo-neurohypophysitis was unlikely. Infectious disease, granulomatosis, Langerhans cell histiocytosis, vasculitis, and systemic neoplastic diseases were excluded by the findings of a laboratory investigation, cerebrospinal fluid examination, and imaging studies. To make a definitive diagnosis, we performed a ventriculoscopic biopsy of the hypothalamic lesion. Histology revealed an infiltration of nonspecific lymphoplasmacytes with no evidence of neoplasm, which was consistent with a diagnosis of idiopathic hypothalamitis. Subsequently, the patient was treated with methylprednisolone pulse therapy followed by oral prednisolone. The hypothalamic lesion improved and remained undetectable after withdrawal of the prednisolone, suggesting that the glucocorticoid treatment was effective for isolated hypothalamitis while the patient remains dependent on the replacement of multiple hormones.

18-Year-old patient with Klinefelter syndrome (47, XXY) and complete androgen insensitivity syndrome (CAIS) - case report.

AIMS: The aims of the presented case report are to emphasize the importance of a proper diagnostics and treatment in the case of the coexistence of Klinefelter syndrome (KS, 47 XXY) and complete androgen insensitivity syndrome (CAIS). Since there is no causal treatment it is necessary to provide the patient with a good quality of life, including psychological and sexological support. MATERIALS AND METHODS: The presented case report is the retrospective analysis of the patient's medical history over the 3 years. RESULTS: At the age of 15, the patient was directed to genetic testing due to primary amenorrhea. The results of the patient showed an incorrect male karyotype with the SRY gene present (47, XXY). A molecular diagnostics revealed a very rare variant of the androgen receptor (AR) mutation responsible for tissue insensitivity to androgens. The detected mutation has not been described in the available databases so far. Following a diagnosis of the presence of Klinefelter syndrome (KS, 47 XXY) together with complete androgen insensitivity syndrome (CAIS), the patient underwent a bilateral gonadectomy. CONCLUSIONS: In women with KS and CAIS physiological reproduction and maintenance of normal sex, hormone levels are not possible. A gonadectomy is performed due to the risk of malignant testicular tumors.

Diagnosis and Surgical Treatment of Uterine Isthmus Atresia: A Case Report and Review of the Literature.

Uterine isthmus atresia is a rare Müllerian duct anomaly occasionally diagnosed in adolescents with primary amenorrhea and cyclic abdominal pain. A case is presented of a 14-year-old female with monthly cyclic lower abdominal pain of a 2-year duration. Magnetic resonance imaging and 3-dimensional ultrasound showed separation of a 10-mm fibrotic tissue between the cervical canal and the endometrial cavity. In an attempt to preserve reproductive ability, an end-to-end anastomosis was laparoscopically performed between the cervical canal and uterine cavity. A platinol stent (WallFlex Biliary RX; Boston Scientific, Boston, MA) was placed by hysteroscopy to avoid stenosis after surgery. Laparoscopic end-to-end anastomosis is proposed to treat congenital uterine isthmus atresia.

Reproductive prognosis of patients with hypogonadotropic hypogonadism: Retrospective review of 16 cases with amenorrhea.

AIM: The aim of this study was to evaluate the general characteristics, menstruation status, and fertility outcomes of patients with hypogonadotropic hypogonadism (HH). METHODS: We evaluated 16 patients with HH who visited our institution between April 2012 and March 2016 with a complaint of amenorrhea. RESULTS: Four (25%) patients had primary amenorrhea and the remaining 12 (75%) cases had secondary amenorrhea. Among the patients with primary amenorrhea, weight loss was considered to be the underlying cause in one (25%) patient, whereas the remaining three (75%) cases were idiopathic HH. Among HH cases with secondary amenorrhea, six (50%) developed amenorrhea following weight loss, whereas the remaining six cases were of unknown etiology. Among the 16 patients with HH, we observed the sporadic restart of the menstrual cycle in four (25%) women during follow-up. Infertility treatment was administered to nine patients with HH who wished to become pregnant. Clomiphene citrate was effective in four patients with secondary amenorrhea and induced follicular development. Seven of nine patients with HH (77.8%) became pregnant following infertility treatment. In some cases of HH, the serum levels of gonadotropin increased sporadically during follow-up, regardless of the recovery of menstruation. We followed one patient with HH for more than 20 years. Although her gonadotropin levels were generally low and sometimes fluctuated without spontaneous menstruation, they increased dramatically to menopausal levels at 50 years of age. However, they again decreased to hypogonadotropic levels. CONCLUSION: As the pathophysiology varied widely among patients, the etiologic factors underlying HH might also vary.