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Copyright of Folia Pharmaceutica Cassoviensia is the property of University of Veterinary Medicine & Pharmacy in Kosice and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and objectives: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background: DICER1, a cancer predisposition syndrome (CPS), seems to escape timely diagnosis in pediatric patients. Case report 1: A 16-year-old female patient was referred to the endocrinology ward due to a large goiter. Her medical history indicated normal sexual maturation, with menarche occurring at 13.5 years. Over the past 2.5 years, she had developed pronounced androgenic symptoms, including a deepened male voice; facial, back, and neckline acne; hirsutism; and menstrual irregularities leading to secondary amenorrhea. A thyroid ultrasound identified a multinodular goiter (MNG) with cystic–solid lesions containing calcifications. An abdominal ultrasound identified a 5.7 × 6.9 cm solid mass in the right adnexal region, displacing the uterus to the left. Histopathological examination confirmed a Sertoli–Leydig cell tumor. The patient was subjected to a total thyroidectomy. Histopathology revealed benign follicular cell-derived neoplasms. Thyroid follicular nodular disease (TFND) was diagnosed bilaterally. DNA analysis using NGS, confirmed via the Sanger method, revealed a pathogenic heterozygotic variant c.2953C>T [p.Gln985*] in exon 18 of the DICER1 gene. Case report 2: A 12-year-old male patient was admitted to the pediatric surgery unit due to a 33 mL goiter. A month prior to his admission, the patient discovered a palpable nodule in his neck, accompanied by hoarseness. An ultrasound revealed MNG. Molecular analysis revealed a pathogenic heterozygotic variant c.2782C>T [p.Gln928*] in exon 17 of the DICER1 gene. Subsequently, a total thyroidectomy was performed, and histopathological examination revealed TFND bilaterally. Conclusions: Recent advances in genetic evaluation and in histological approaches indicate that MNG/TFND, although rare in the pediatric population, when accompanied by characteristic ultrasound and histopathological features, and by additional features such as androgenization, may warrant assessment also of the DICER1 gene within CPS molecular panel screening. [ABSTRACT FROM AUTHOR]

Copyright of Romanian Journal of Family Medicine / Revista Română de Medicina Familiei is the property of Media DOM Express and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Menstruation is an important physiological function of the female reproductive system. The absence of menstruation is called amenorrhea. Many genetic and nongenetic causes are responsible for primary or secondary amenorrhea. This study aimed to determine the types chromosomal abnormalities among patients with primary or secondary amenorrhea. Methods: It was a cross-sectional study conducted in the Department of Pathology, Bangabandhu Sheikh Mujib Medical University, Dhaka, from September 2019 to August 2021. A total of 115 women who had come for a karyotype test with complaints of pathological amenorrhea were purposively selected. One hundred five cases presented with primary amenorrhea, and 10 cases presented with secondary amenorrhea. Karyotype analysis in peripheral blood by G-banding was carried out using the standard method. Results: Among the 105 patients with primary amenorrhea, 53.3% of patients had a normal karyotype (46, XX), and 46.6% had chromosomal abnormalities (numerical or structural). Turner syndrome classic, 45, XO (16.2%) and 46, XY DSD (Disorders of Sexual Development) (11.4%) were the two most frequent chromosomal abnormalities found in the patients with primary amenorrhea. Among the 10 cases with secondary amenorrhea, seven patients had normal karyotype, and three patients had chromosomal abnormalities (2 had sex chromosomal abnormalities, and 1 had a structural abnormality of autosome). Conclusion: The study of chromosomal abnormalities will help in the early and accurate diagnosis of the underlying aetiology of primary or secondary amenorrhea. It will also help in the management and proper counselling of cases.

Novina Novina,1 Mulyanusa Amarullah Ritonga,2 Aliyya Salsabila Yusuf3 1Department of Child Health, Faculty of Medicine, Universitas Padjadjaran / Hasan Sadikin General Hospital, Bandung, West Java, Indonesia; 2Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Padjadjaran / Hasan Sadikin General Hospital, Bandung, West Java, Indonesia; 3Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, IndonesiaCorrespondence: Novina Novina, Department of Child Health, Faculty of Medicine, Universitas Padjadjaran / Hasan Sadikin General Hospital, Jl. Pasteur No. 38 Kel. Pasteur Kec. Sukajadi, Bandung, 40161, Indonesia, Tel/Fax +62 22 2035957, Email novina@unpad.ac.idPurpose: To provide characteristics and hormonal profiles of secondary amenorrhea cases in adolescent patients treated at Hasan Sadikin General Hospital in Bandung.Patients and Methods: The study was retrospective in nature and involved the analysis of medical records from 2017 to 2022 for 44 adolescent patients aged 10– 18 who had secondary amenorrhea.Results: There were 44 adolescents included in this study after excluded 69 adults from 113 secondary amenorrhea cases. The majority of patients were 14– 17 years old (38.63%), in senior high school (45.45%), had started menarche at 11 years old (45.45%), had normal nutritional status (65.91%), and had normal stature (65.91%). The underlying diseases found in most patients were systemic lupus erythematosus (SLE) and tuberculosis. Among the patients, 29 had FSH, LH, and estradiol levels measured. The results of hormonal assays showed a wide range of abnormal serum levels, with normal to low concentrations of FSH and low levels of LH and estradiol. The median (interquartile range) results for FSH, LH, and estradiol were 4.57 (0.64, 90.65), 1.635 (0.06, 55.76), and 24.3 (0.2, 154.71), respectively. Positive significant correlation between FSH and LH (p < 0.01) was found in children with secondary amenorrhea.Conclusion: Hormonal assay for FSH, LH, and Estradiol showed a wide range of abnormal serum level. Normal to low concentration levels of FSH and low LH and estradiol. The majority of secondary amenorrhea patients are associated with autoimmune disease and infection.Keywords: adolescent, follicle-stimulating hormone, estradiol, luteinizing hormone, secondary amenorrhea, underlying disease

Abstract Objective Premature ovarian insufficiency (POI) is characterized by early hypoestrogenism. An increased risk of cardiovascular (CV) disease is a long-term consequence of POI. A challenge of hormone therapy (HT) is to reduce the CV risk. Methods Cross-sectional study with lipid profile analysis (total cholesterol, LDL-C, HDL-C, VLDL-C and triglycerides), blood glucose levels and arterial blood pressure of women with POI using HT, compared with age and BMI-matched women with normal ovarian function (controls). Results The mean age and BMI of 102 POI patients using HT and 102 controls were 37.2 ± 6.0 and 37.3 ± 5.9 years, respectively; 27.0 ± 5.2 and 27.1 ± 5.4 kg/m2. There wasn't difference between groups in arterial systolic and diastolic blood pressure, blood glucose levels, total cholesterol, LDL-C, VLDL-C and triglycerides. HDL-C levels were significantly higher in the POI group (56.3 ± 14.6 and 52 ± 13.9mg/dL; p = 0.03). Arterial hypertension was the most prevalent chronic disease (12% in the POI group, 19% in the control group, p = ns), followed by dyslipidemia (6 and 5%, in POI and control women). Conclusion Women with POI using HT have blood pressure levels, lipid and glycemic profile and prevalence of hypertension and dyslipidemia similar to women of the same age and BMI with preserved gonadal function, in addition to better HDL levels.

Background and objectives: 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. Results: 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. Conclusions: 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.

Background: Amenorrhea, the medical term for the absence of menstruation, can lead to infertility and, consequently, have profound societal implications. This case-control study aimed to investigate the association between hyperprolactinemia and thyroid hormone levels in individuals experiencing amenorrhea. Methods: We conducted hormonal evaluations on 50 UCMS hospital patients who had been diagnosed with secondary amenorrhea. Fifty-two women who were otherwise healthy served as controls. Cases and controls were analyzed for thyroid dysfunction and serum prolactin levels. Results: An intriguing revelation emerged from the study: patients exhibited notably higher average prolactin levels in their serum compared to the control group. When juxtaposing hyperprolactinemic and normoprolactinemic individuals, the former displayed marginally reduced average serum fT3 and fT4 levels, with comparable mean TSH levels across both groups (P=0.049). Prolactin's relationship with BMI, TSH, and age proved positive, while it conversely correlated with fT3, fT4, and chronological years. Moreover, hyperprolactinemic subjects experienced a negative correlation between prolactin and TSH (r=-0.115, P=0.481), normoprolactinemic counterparts displayed a positive correlation (r=0.296, P=0.126). Conclusions Assessing amenorrhea diagnostically calls for measuring prolactin, fT3, fT4, and TSH levels, as the interplay of hyperprolactinemia and thyroid dysfunction could be key hormonal factors in the equation. [ABSTRACT FROM AUTHOR]

The purpose of the study was to evaluate the prevalence, co-morbidities, pharmacological therapy, and effectiveness of common lifestyle changes for metabolic dysfunction in women with the polycystic ovarian syndrome (PCOS) and related comorbidities in the gynaecology division. This 6-month prospective observational study of 120 PCOS patients who were gynaecology patients at a tertiary care hospital was conducted from September 2021 to February 2022. An interview with the patient was done using an assessment form. This study highlighted the supportive evidence among PCOS patients for the advantages of changing one's lifestyle. This study involved 90 PCOS individuals out of a total of 120 participants, many of them were in the 20–30 age group. This research analyses the high prevalence of cardiovascular disease co-morbidities and demonstrates that a high BMI is the most common risk factor for PCOS. The findings of our study indicate the necessity of evaluating the complications seen in individuals who are at risk, such as infertility. This line of research demonstrates the critical impact that medication and lifestyle modifications play in managing PCOS. Patients with the polycystic ovarian syndrome should get advice regarding lifestyle modifications from a clinical pharmacist.

Copyright of Pediatric Endocrinology, Diabetes & Metabolism is the property of Termedia Publishing House and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: DICER1, a cancer predisposition syndrome (CPS), seems to escape timely diagnosis in pediatric patients. Case report 1: A 16-year-old female patient was referred to the endocrinology ward due to a large goiter. Her medical history indicated normal sexual maturation, with menarche occurring at 13.5 years. Over the past 2.5 years, she had developed pronounced androgenic symptoms, including a deepened male voice; facial, back, and neckline acne; hirsutism; and menstrual irregularities leading to secondary amenorrhea. A thyroid ultrasound identified a multinodular goiter (MNG) with cystic–solid lesions containing calcifications. An abdominal ultrasound identified a 5.7 × 6.9 cm solid mass in the right adnexal region, displacing the uterus to the left. Histopathological examination confirmed a Sertoli–Leydig cell tumor. The patient was subjected to a total thyroidectomy. Histopathology revealed benign follicular cell-derived neoplasms. Thyroid follicular nodular disease (TFND) was diagnosed bilaterally. DNA analysis using NGS, confirmed via the Sanger method, revealed a pathogenic heterozygotic variant c.2953C>T [p.Gln985*] in exon 18 of the DICER1 gene. Case report 2: A 12-year-old male patient was admitted to the pediatric surgery unit due to a 33 mL goiter. A month prior to his admission, the patient discovered a palpable nodule in his neck, accompanied by hoarseness. An ultrasound revealed MNG. Molecular analysis revealed a pathogenic heterozygotic variant c.2782C>T [p.Gln928*] in exon 17 of the DICER1 gene. Subsequently, a total thyroidectomy was performed, and histopathological examination revealed TFND bilaterally. Conclusions: Recent advances in genetic evaluation and in histological approaches indicate that MNG/TFND, although rare in the pediatric population, when accompanied by characteristic ultrasound and histopathological features, and by additional features such as androgenization, may warrant assessment also of the DICER1 gene within CPS molecular panel screening.

ABSTRACT BACKGROUND: Chromosomal abnormalities (CAs) have been described in patients with secondary amenorrhea (SA). However, studies on this association are scarce. OBJECTIVES: To evaluate the frequency and types of CAs detected by karyotyping in patients with SA. DESIGN AND SETTING: This retrospective study was performed in a reference clinical genetic service in South Brazil. METHODS: Data were obtained from the medical records of patients with SA who were evaluated between 1975 and 2022. Fisher’s bicaudate exact test and Student’s t-test were used, and P < 0.05 was considered significant. RESULTS: Among 43 patients with SA, 14 (32.6%) had CAs, namely del (Xq) (n = 3), 45,X (n = 2), 46,X,r(X)/45,X (n = 2), 46,XX/45,X (n = 1), 46,X,i(q10)/45,X (n = 1), 47,XXX (n = 1), 46,XX/47,XXX (n = 1), 46,XX/47,XX,+mar (n = 1), 45,XX,trob(13;14)(q10;q10)/46,XXX,trob(13;14)(q10;q10) (n = 1), and 46,XX,t(2;21)(q23;q11.2) (n = 1). Additional findings were observed mostly among patients with CA compared with those without CA (P = 0.0021). No difference in the mean age was observed between the patients with SA with or without CAs (P = 0.268025). CONCLUSIONS: CAs are common among patients with SA, especially those with short stature and additional findings. They are predominantly structural, involve the X chromosome in a mosaic, and are compatible with the Turner syndrome. Patients with SA, even if isolated, may have CAs, particularly del (Xq) and triple X.

Secondary amenorrhea is the absence of menses for more than 3 months in women who previously had regular menstrual cycles or 6 months for those with irregular cycles. Workup of secondary amenorrhea includes laboratory analysis to assess pituitary function, specifically luteinizing hormone (LH) and follicle stimulating hormone (FSH). If low, structural evaluation of the pituitary gland with MRI is recommended. We report a case of a 31-year-old female with history of transfusion-dependent Diamond-Blackfan anemia and type 2 diabetes that reported amenorrhea for 1 year following intrauterine device (IUD) removal. Due to low LH and FSH, the patient underwent an MRI of the pituitary gland. Imaging demonstrated complete absence of MRI signal within the pituitary parenchyma, which confirmed pituitary dysfunction from secondary hemochromatosis, presumably due to iron overload from multiple transfusions. As a result of her imaging and laboratory assessment, she was placed on an iron chelator and oral contraception., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Background: Premature ovarian insufficiency (POI) is defined as the onset of a menopausal state prior to 40 years of age. Of the various causes of POI, genetic abnormalities account for 10.8% of all cases, which can be categorized into either chromosomal or gene anomalies. Chromosomal abnormalities of the isochromosome Xq [i(Xq)] type have been recognized as common causes of POI. Cases: A 16-year-old female presented with secondary amenorrhea that had persisted for one year. Her physical examination was unremarkable, including a height of 158 cm and the presence of secondary sexual characteristics. Her serum level of follicle-stimulating hormone was elevated (66 mIU/mL), whereas her estradiol and anti-Müllerian hormone levels were decreased (

Background: Nearly 90% of all the hormone-producing ovarian tumours are sex cord-stromal tumours (SCSTs). The Ovarian fibroma is a hormonally inactive variant of SCST. It is composed of spindle, oval, round cells producing collagen and accounts for approximately 4% of all ovarian neoplasms. Amongst the other SCSTs, Inhibin B is an important tumour marker. It is a heterodimeric glycoprotein hormone that is secreted primarily by the granulosa cells of the developing follicles. High levels of Inhibin-B can hamper follicular recruitment, leading to amenorrhea in a reproductive age woman. Finding: In this case report, we describe a rare case of a reproductive age female presenting with secondary amenorrhea, having an Ovarian Fibroma, producing massive amounts of Inhibin B. Significance: Although some pathological variants of ovarian fibromas like cyst-adeno-fibroma and ovarian fibro-thecoma are known to secrete inhibin B, benign /pure ovarian fibromas rarely do so. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency is considered a major public health problem worldwide and has been reported as having an association with depression. However, studies on the association between vitamin D deficiency and depressive symptoms in secondary amenorrhea (SA) patients are still scarce. This study examined the relationship between serum 25-hydroxyvitamin D (25(OH)D) levels and depressive symptoms among Korean women with SA. In this cross-sectional observational study, 78 patients with SA were initially recruited. Clinical and biochemical parameters, including serum 25(OH)D level, were measured. Data from 63 SA patients who met the study inclusion criteria and completed psychiatric assessments were finally analyzed. We analyzed their association with depression using a hierarchical regression model. The average serum 25(OH)D level was 34.40 ± 24.02 ng/mL, and 41.3% of the women with SA were vitamin D-deficient (<20 ng/mL). The total score of the Korean version of the Hamilton Depression Rating Scale (K-HDRS) was negatively related to serum 25(OH)D levels, free testosterone, and serum anti-Müllerian hormone (AMH) after adjusting for age and BMI (r = −0.450, p < 0.001; r = −0.258, p = 0.045; and r = −0.339, p = 0.006, respectively). Serum 25(OH)D levels and AMH levels were the most powerful predictors of depressive severity when using the K-HDRS in SA patients (β = −0.39, p < 0.005; β = −0.42, p < 0.005, respectively). This study showed that low serum 25(OH)D levels were associated with the severity of depressive symptoms in SA patients. This observation suggests that the evaluation of vitamin D deficiency for the risk of depression may be necessary in patients with SA. [ABSTRACT FROM AUTHOR]

Premature ovarian insufficiency (POI) has a strong genetic component, but, in most cases, the etiology remains unidentified. PSMC3IP is an autosomal recessive gene for POI and ovarian dysgenesis, and so far, biallelic mutations in this gene have been described in only four independent families, with all affected members showing primary amenorrhea. Here, we report on the first family with recessive variants in the PSMC3IP gene and POI in a patient with secondary amenorrhea. Whole-exome sequencing (WES) was performed on a 29-year-old woman with secondary amenorrhea and POI; she was found to carry compound heterozygous variants in the PSMC3IP gene: c.206_208delAGA and c.189 G > T. Her younger sister, who also presented with a suspect of POI due to infertility and very low levels of anti-müllerian hormone (AMH), was found to carry the same PSMC3IP variants. Our case report shows the importance to include PSMC3IP in designed POI NGS panels or in WES/WGS studies in patients with either primary or secondary amenorrhea. [ABSTRACT FROM AUTHOR]

Menstrual cyclicity is a marker of health for reproductively mature women. Absent menses, or amenorrhea, is often the initial sign of pregnancy--an indication that the system is functioning appropriately and capable of generating the intended evolutionary outcome. Perturbations of menstrual regularity in the absence of pregnancy provide a marker for physiological or pathological disruption of this well-orchestrated process. New-onset amenorrhea with duration of 3 to 6 months should be promptly evaluated. Secondary amenorrhea can reflect structural or functional disturbances occurring from higher centers in the hypothalamus to the pituitary, the ovary, and finally, the uterus. Amenorrhea can also be a manifestation of systemic disorders resulting in compensatory inhibition of reproduction. Identifying the point of the breakdown is essential to restoring reproductive homeostasis to maintain future fertility and reestablish reproductive hormonal integrity. Among the most challenging disorders contributing to secondary amenorrhea is primary ovarian insufficiency (POI). This diagnosis stems from a number of possible etiologies, including autoimmune, genetic, metabolic, toxic, iatrogenic, and idiopathic, each with associated conditions and attendant medical concerns. The dual assaults of unanticipated compromised fertility concurrently with depletion of the normal reproductive hormonal milieu yield multiple management challenges. Fertility restoration is an area of active research, while optimal management of estrogen deficiency symptoms and the anticipated preventive benefits of hormone replacement for bone, cardiovascular, and neurocognitive health remain understudied. The state of the evidence for an optimal, individualized, clinical management approach to women with POI is discussed along with priorities for additional research in this population. [ABSTRACT FROM AUTHOR]

Primary ovarian insufficiency (POI) is one of the major causes of female infertility associated with the premature loss of ovarian function in about 3.7% of women before the age of 40. This disorder is highly heterogeneous and can manifest with a wide range of clinical phenotypes, ranging from ovarian dysgenesis and primary amenorrhea to post-pubertal secondary amenorrhea, with elevated serum gonadotropins and hypoestrogenism. The ovarian defect still remains idiopathic in some cases; however, a strong genetic component has been demonstrated by the next-generation sequencing (NGS) approach of familiar and sporadic POI cases. As recent evidence suggested an oligogenic architecture for POI, we developed a target NGS panel with 295 genes including known candidates and novel genetic determinants potentially involved in POI pathogenesis. Sixty-four patients with early onset POI (range: 10–25 years) of our cohort have been screened with 90% of target coverage at 50×. Here, we report 48 analyzed patients with at least one genetic variant (75%) in the selected candidate genes. In particular, we found the following: 11/64 patients (17%) with two variants, 9/64 (14%) with three variants, 9/64 (14%) with four variants, 3/64 (5%) with five variants, and 2/64 (3%) with six variants. The most severe phenotypes were associated with either the major number of variations or a worse prediction in pathogenicity of variants. Bioinformatic gene ontology analysis identified the following major pathways likely affected by gene variants: 1) cell cycle, meiosis, and DNA repair; 2) extracellular matrix remodeling; 3) reproduction; 4) cell metabolism; 5) cell proliferation; 6) calcium homeostasis; 7) NOTCH signaling; 8) signal transduction; 9) WNT signaling; 10) cell death; and 11) ubiquitin modifications. Consistently, the identified pathways have been described in other studies dissecting the mechanisms of folliculogenesis in animal models of altered fertility. In conclusion, our results contribute to define POI as an oligogenic disease and suggest novel candidates to be investigated in patients with POI. [ABSTRACT FROM AUTHOR]

Primary ovarian insufficiency (POI) is one of the major causes of female infertility associated with the premature loss of ovarian function in about 3.7% of women before the age of 40. This disorder is highly heterogeneous and can manifest with a wide range of clinical phenotypes, ranging from ovarian dysgenesis and primary amenorrhea to post-pubertal secondary amenorrhea, with elevated serum gonadotropins and hypoestrogenism. The ovarian defect still remains idiopathic in some cases; however, a strong genetic component has been demonstrated by the next-generation sequencing (NGS) approach of familiar and sporadic POI cases. As recent evidence suggested an oligogenic architecture for POI, we developed a target NGS panel with 295 genes including known candidates and novel genetic determinants potentially involved in POI pathogenesis. Sixty-four patients with early onset POI (range: 10–25 years) of our cohort have been screened with 90% of target coverage at 50×. Here, we report 48 analyzed patients with at least one genetic variant (75%) in the selected candidate genes. In particular, we found the following: 11/64 patients (17%) with two variants, 9/64 (14%) with three variants, 9/64 (14%) with four variants, 3/64 (5%) with five variants, and 2/64 (3%) with six variants. The most severe phenotypes were associated with either the major number of variations or a worse prediction in pathogenicity of variants. Bioinformatic gene ontology analysis identified the following major pathways likely affected by gene variants: 1) cell cycle, meiosis, and DNA repair; 2) extracellular matrix remodeling; 3) reproduction; 4) cell metabolism; 5) cell proliferation; 6) calcium homeostasis; 7) NOTCH signaling; 8) signal transduction; 9) WNT signaling; 10) cell death; and 11) ubiquitin modifications. Consistently, the identified pathways have been described in other studies dissecting the mechanisms of folliculogenesis in animal models of altered fertility. In conclusion, our results contribute to define POI as an oligogenic disease and suggest novel candidates to be investigated in patients with POI.

APS (autoimmune polyglandular syndrome) is defined as the coexistence of at least two kinds of endocrine autoimmune diseases. APS type 3 comprises autoimmune thyroid diseases and other autoimmune diseases but does not involve autoimmune Addison’s disease. So far, APS-3 combined with isolated gonadotropin-releasing hormone (GnRH) reduction caused by the suspected autoimmune hypothalamic disease has not been reported. We recently received a 43-year-old woman with a one-year history of Graves’ disease (GD) and a four-month history of type 1 diabetes presented with hyperthyroidism and hyperglycemia. After the GnRH stimulation test, she was diagnosed with secondary amenorrhea attributed to suspected autoimmune Hypothalamitis and APS type 3 associated with Graves’ disease and Latent Autoimmune Diabetes (LADA). According to this case, the hypothalamus cannot be spared from the general autoimmune process. It is recommended to carry out the GnRH stimulation test when encountering APS patients combined with secondary amenorrhea.

APS (autoimmune polyglandular syndrome) is defined as the coexistence of at least two kinds of endocrine autoimmune diseases. APS type 3 comprises autoimmune thyroid diseases and other autoimmune diseases but does not involve autoimmune Addison's disease. So far, APS-3 combined with isolated gonadotropin-releasing hormone (GnRH) reduction caused by the suspected autoimmune hypothalamic disease has not been reported. We recently received a 43-year-old woman with a one-year history of Graves' disease (GD) and a four-month history of type 1 diabetes presented with hyperthyroidism and hyperglycemia. After the GnRH stimulation test, she was diagnosed with secondary amenorrhea attributed to suspected autoimmune Hypothalamitis and APS type 3 associated with Graves' disease and Latent Autoimmune Diabetes (LADA). According to this case, the hypothalamus cannot be spared from the general autoimmune process. It is recommended to carry out the GnRH stimulation test when encountering APS patients combined with secondary amenorrhea. [ABSTRACT FROM AUTHOR]

This article provides an approach to amenorrhea and is intended for pre-clinical and clerkship medical students. Primary amenorrhea refers to the absence of menarche by 15 years or 3 years post thelarche while secondary amenorrhea is the cessation of menses for 3 months inwomen with a previously regular cycle or for 6 months in women with previously irregular menses. While amenorrhea can be physiological it can also reflect an anatomical or more complex hormonal problem that students must learn to identify and investigate. [ABSTRACT FROM AUTHOR]

This is a pictorial review on the radiological approach to patients with amenorrhea using a level-based framework. The prevalence of amenorrhea is 3 to 4% with wide-ranging causes involving multiple clinical disciplines. Normal menstruation depends on complex coordinated hormonal functions of the hypothalamic–pituitary–ovarian axis exerting its effect on an intact uterine end-organ and outflow tract. A disruption of any of these factors may result in amenorrhea. Categorizing the causes of primary and secondary amenorrhea into uterine, ovarian/gonadal, and intracranial levels provides a logical framework for its evaluation. A systematic level-based approach by targeted ultrasound of the pelvic structures is suggested, with different aims in primary versus secondary amenorrhea. Pelvic sonographic findings of various conditions within the uterine and ovarian/gonadal levels are illustrated. Conditions due to an intracranial cause result in downstream effects on the uterus and ovaries and can often be suspected based on a combination of clinical assessment, ultrasound findings, and laboratory investigations. By correlating pelvic ultrasound findings with underlying pathology, the clinical radiologist is able to provide useful diagnostic information in the management of these patients. [ABSTRACT FROM AUTHOR]

Perforated transverse vaginal septum (TVS) leading to secondary amenorrhea in unmarried girl is a rare entity. A 20 years old unmarried girl presented to gynaecology OPD with history of amenorrhea since one month and 12 days, pain lower abdomen with swelling since 7 days and difficulty in voiding urine since 2 days. She had history of regular menstrual cycles since the age of 13 years. Local examination revealed pinkish mass bulging through introitus. MRI showed vaginal outlet obstruction with haematocolpos and haematometra. Diagnosis was confirmed and case was successfully managed during examination under anaesthesia. This case highlights the evolution from perforated transverse low vaginal septum with normal and regular menstrual cycles to a complete septum (due to retained menstrual blood and tissue debris) which leads to secondary amenorrhea.

Background: Menarche is an important milestone in a feminine reproductive life, and regular menstrual cycles reflect normal functioning of the hypothalamic-pituitary-ovarian axis, a vital sign of women's general health. Aim of the study: We explored the age at menarche and the following menstrual cycles characteristics among 85 unmarried Transfusion-Dependent ß-Thalassemia (TDT) women, born between 1965 and 1995, concerning iron chelation therapy (ICT) with desferrioxamine (DFO) and nutritional status, assessed by body mass index (BMI). Results: 53 adolescents who had begun ICT before the age of 10 years experienced menarche at 13,7 ± 1,6 years (mean ± DS), whereas 32 who began treatment after ten years experienced menarche significantly later (15.5 ± 1.9 yrs; p: 0.001). At the age of menarche: BMI-Z score (n= 67, - 0,09 ±1) was inversely correlated with both age at starting ICT (r = - 0,39; p = 0001) and age at menarche (- 0,45, p = 0,0001). Serum ferritin levels (SF) were significantly correlated with the age at starting chelation therapy (n = 79; r = 0,34; p = 0,022). In 56 TDT adolescents who developed secondary amenorrhea (SA), the SF levels were significantly higher (4,098 ± 1,907 ng/mL) compared to 23 TDT adolescents with regular menstrual cycles (2,913±782 ng/mL; p = 0,005). Nutritional status of "thinness" at menarche was associated with a lower prevalence of subsequent regular menstrual cycles and a higher prevalence of early SA. Conclusion: An early ICT in TDT patients was associated with a normal "tempo" of pubertal onset and a higher frequency of subsequent regular menstrual cycles. In TDT patients, who developed SA, a diagnosis of acquired central hypogonadism was made, mainly due to the chronic exposure to iron overload, however other potential causes linked to nutritional status, deficient levels of circulating nutrients, and the chronic disease itself cannot be fully excluded. [ABSTRACT FROM AUTHOR]

Secondary amenorrhea is not uncommon in the adolescent female population. There are multiple etiologies to consider, and a comprehensive evaluation is often pursued. Sometimes, however, despite a thorough workup, the diagnosis remains unclear. Here, we report an unusual cause of secondary amenorrhea in a 15-year-old girl. Our patient presented with secondary amenorrhea after a 4-year history of regular menstrual cycles. Her evaluation was notable for very low FSH and low estradiol but normal LH; pregnancy, adrenal, thyroid, prolactin studies, and brain magnetic resonance imaging scan did not reveal a cause of her amenorrhea. Her transabdominal ultrasound showed an enlarged right ovary, initially suggestive of a hemorrhagic cyst. Inhibin A and B were measured because of the persistently low FSH; these were found to be very elevated, concerning for an inhibin-producing tumor. The patient had surgical removal of her right ovary; pathology revealed a juvenile granulosa-cell tumor. Postoperatively, the patient had normalization of serum inhibin A and B and resumption of normal menstrual cycles. This report illustrates that careful consideration of laboratory findings and other studies is essential for correctly identifying the underlying cause of secondary amenorrhea, particularly when the results are not consistent with common causes of this condition. [ABSTRACT FROM AUTHOR]

Objective: To determine whether secondary amenorrhea during teenage years influences bone mineral density (BMD) in female athletes in their 20s. Design: Original research. Setting: Japan Institute of Sports Sciences. Participants: Two hundred ten elite female athletes older than 20 years were included in the study. Main Outcome Measures: Information on the participants' past (ie, during their teenage years) and current menstrual cycle, training time, history of stress fractures, and blood tests for hormones received was obtained. Bone mineral density of the lumbar spine was evaluated by dual-energy x-ray absorptiometry; low BMD was defined as a Z-score ≤-1. We investigated the correlation factors for low BMD in athletes in their 20s by univariable and multivariable logistic regression analysis. Results: A total of 39 (18.6%) female athletes had low BMD. Secondary amenorrhea in their teens [odds ratio (OR), 7.11, 95% confidence interval (CI), 2.38-21.24; P < 0.001] and present body mass index (BMI) (OR, 0.56, 95% CI, 0.42-0.73; P < 0.001) were independent correlation factors for low BMD in the multivariable logistic regression analysis. The average Z-score for those with secondary amenorrhea in their teens and 20s, secondary amenorrhea in their 20s only, and regular menstruation was -1.56 ± 1.00, -0.45 ± 1.21, and 0.82 ± 1.11 g/cm2, respectively. Conclusions: Secondary amenorrhea for at least 1 year during teenage years in female athletes and BMI at present was strongly associated with low BMD in their 20s. [ABSTRACT FROM AUTHOR]

To detect the frequency of secondary amenorrhea in a cohort of Egyptian systemic lupus erythematosus (SLE) patients and to identify potentially related key-players. The medical records of 140 adult SLE patients above 18 and less than 40 years were revised regarding clinical characteristics, immunological features and medications received. The SLE disease activity index (SLEDAI) and damage index (SLICC-DI) were recorded. Patients were divided into two groups: patients who developed secondary amenorrhea and those having normal menstrual cycles. The mean age of the patients was 26.8 ± 5.7 years, the median disease duration was 3.5 years. The patients had renal involvement in 69.3%, neuropsychiatric in 23.6% and cardiac in 37.9%. Cyclophosphamide (CYC) was received by 52.1% and steroids by 139 patients. Secondary amenorrhea was found in 44 patients (31.4%); 36 (81.8%) of them were ≤32 years old. Patients with secondary amenorrhea had a higher frequency of positive anti-double stranded deoxyribonucleic acid (ds-DNA) antibodies (75% vs 50%; p = 0.04) and a shorter disease duration (median 2 years vs 4.5 years; p = 0.005). Lupus nephritis, renal failure, neuropsychiatric manifestations, cardiac involvement and receiving CYC and high-dose steroids tended to be more frequent in those with secondary amenorrhea compared to those without. The median SLICC-DI was higher in those with amenorrhea compared to those without (p = 0.2) Cyclophosphamide is not the only key-player for the development of secondary amenorrhea in SLE; other factors as the shorter disease duration, presence of autoantibodies and major organ involvements may be implicated. [ABSTRACT FROM AUTHOR]

Objectives: In Japan, the prevalence of irregular menstrual cycles and its association with the frequency of night shifts have scarcely assessed. The present study aimed to evaluate the relationship between irregular menstrual cycles and the frequency of night shifts in Japanese female nurses. Methods: We conducted a cross‐sectional web‐based self‐administered questionnaire survey in 2019. An irregular menstrual cycle was defined as a cycle length of ≤21 days or ≥39 days at least a few times over the past year or amenorrhea for at least 3 months. We used Poison regression analysis with a robust error variance to calculate the prevalence ratios adjusted for age, body mass index, hospital size, and the department in which they worked. Results: A total of 1249 women were included, and 679 (54.4%) and 195 (15.6%) of them worked under two and three rotating shifts. The prevalence of irregular menstrual cycles was 24.8%, 37.4%, and 35.9% in the no night, two rotating, and three rotating shifts groups, respectively. While the frequency of night shifts had a dose‐responsive relationship with irregular menstrual cycles in the two rotating shifts group, it was not observed in the three rotating shifts group. However, the risk of work getting affected by dysmenorrhea or premenstrual symptoms increased in the three rotating shifts group. Conclusions: Over 30% of Japanese female nurses working under night shifts had irregular menstrual cycles. The high frequency of night shifts increased the risk of irregular menstrual cycles and secondary amenorrhea in the two rotating shifts group. [ABSTRACT FROM AUTHOR]

Background: Secondary amenorrhea is a condition when period cycle of women with irregular menstruation disappeared within six months in a row or; when the period cycle of regular menstruation women disappeared during three months in a row. In Traditional Chinese Medicine (TCM), amenorrhea is known as Jing Bi. The patient in this study case was having secondary amenorrhea with menstrual complaints not within 3 months and 22 days after the last periods. Patient was classified as secondary amenorrhea with differentiation of Qi and blood deficiency syndrome. Purpose: To know the effect of acupuncture therapy with Sanyinjiao point (SP6), Taichong point (LR3), Zusanli point (ST36), Gui lai point (ST 29) combined with turmeric herbal therapy (Curcuma domestica Val) and klabet seed (Trigonella foenum-graecum L.) in patients with secondary amenorrhea. Methods: Treatment of this secondary amenorrhea case was using acupuncture and herbal therapy. Acupuncture therapy at acupoint Sanyinjiao (SP6), Taichong (LR3), Zusanli (ST36), and Gui Lai (ST29) with tonification principle of Qi and blood and improve menstrual flow. The herbal therapy given were turmeric (Curcuma domestica Val) and fenugreek seeds (Trigonellafoenum-graecum L.), which has estrogenic effect. Results: Estrogen stimulates the lining of the uterus to remove the menstrual blood. In the treatment of secondary amenorrhea, acupuncture therapy was given 21 times, three times a week. Herbal therapy was given for 60 days, taken 2 times a day with dose of 15 grams of turmeric and 4 grams of fenugreek seeds. This therapy might help the menstrual blood exuviation. Conclusion: Acupuncture and herbal therapy can be applied continously to the patient up until regular period cycle are attained.

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Premature ovarian insufficiency (POI) defined as a resolution of menstruation and ovarian function before 40 years of age, affects about 0,01% young women under 20 years old [1-3]. Hormonal tests reveal elevated FSH, low estradiol and anti-Muellerian hormone level (AMH) [1-3]. The etiology of POI is highly heterogenous, it manifests as primary or secondary amenorrhea. Diagnostic process includes several genetical disorders, endocrine or metabolic diseases, autoimmune processes or iatrogenic procedures [1,2,4]. Main health problems are low fertility or infertility, psychological problems and metabolic effects of hypoestrogenism leading to low bone mineral density and cardiovascular diseases. For these reasons hormone replacement therapy should be applied in patients diagnosed with POI [1,2,5]. We present the case of 17,5 year-old girl with autoimmune thyroiditis (hypothyroidism) and POI, presenting secondary amennorrhoea at the age of 15 with no familiar history of menstruation disorders, and literature review. [ABSTRACT FROM AUTHOR]

Pituitary insufficiency is an uncommon disorder. The most common cause is compression due to a pituitary mass. Other causes include inflammatory damage and vascular injury like postpartum pituitary apoplexy. Postpartum pituitary apoplexy, also known as Sheehan's syndrome, leads to hormonal deficiencies and causes postpartum amenorrhea, lactational failure, chronic hyponatremia, hypoglycemia, and loss of secondary sexual characters. Here we are discussing the clinical course of 15 female patients of panhypopituitarism. Most of them had a history of postpartum hemorrhage. Knowledge about this entity is essential as it is a treatable condition and ignorance could prove to be fatal. [ABSTRACT FROM AUTHOR]

Background: Relatively few studies have assessed psychosocial correlates for secondary amenorrhea. Our study of the Gynaecological condition concerning personality factor (on introversion-extroversion dimension), parenting (authoritarian and authoritative) style, depression and perceived stress addresses this gap in the literature. The study inquires, whether these variables are related. Aims and objectives: To evaluate the relation of personality, parenting, stress and depression in patients with secondary amenorrhoea. Methods: Evaluation was done for forty-four young-adult female patients (with their fathers alive) affected by secondary amenorrhea, requesting help for menstrual disorders. The Parental Authority Questionnaire administered on the parent of patients, and Beck Depression Inventory, Perceived stress scale, Kundu Introversion-Extraversion Inventory on patients. In addition to that sixty healthy participants were recruited. The 104 participants were divided into two groups according to the presence (44 cases) or the absence (60 cases) of clinically diagnosed secondary amenorrhea. Results: Appropriate use of correlation coefficient followed by a test of significance revealed significant correlations between the variables which were hypothesised in accordance and hadbeen discussedregarding future research. Conclusions: Secondary amenorrhea was found to be possibly associated with personality factors, stress, depression and the kind of parenting individuals receive during their lifetime.

Abstract In this paper, a case of premature ovarian failure(POF), accompanied with amenorrhea for 2 years was reported. After 2 months of acupuncture, the patient's menstruation was resumed, and after 11 months of treatment, the patient had a spontaneous pregnancy. It is suggested that acupuncture should be used for the patient with POF as early as possible, and if necessary, hormone replacement therapy is still needed, and it is still expected to obtain spontaneous pregnancy before completely exhausted of ovarian function. [ABSTRACT FROM AUTHOR]

Blepharophimosis ptosis epicanthus inversus (BPES) is a relatively rare congenital disorder, which usually presents with classical eye manifestations. In some cases, it is associated with premature ovarian failure (POF). BPES is of two types, type I and type II. Type I is associated with POF along with eyelid malformations, while Type 2 has only eyelid malformations. Here, we report a family of BPES, in whom two sisters presented with secondary amenorrhea. On eye examination, they have blepharophimosis, ptosis, epicanthus inversus and telecanthus. Investigations revealed hypergonadotropic hypogonadism. Their father also has similar eye manifestations. Diagnosis of BPES type I was made and both were started on hormone replacement therapy. To make timely diagnosis of BPES, every patient with POF should specifically be checked for eye manifestations.

Perinatal histories of 172 adolescent girls aged 13–17 years with secondary amenorrhea (SA) and 102 age-matched girls with regular menstrual cycle (comparison group), and reproductive status of their mothers have been studied. It has been found that the most unfavorable factor affecting the formation of SA in adolescent girls is the late menarche in their mothers. It is found that the probability of SA in girls born from the mothers with late menarche right after menarche or after previous menstrual disorders is 16-fold increased. Ir is determined that particularly unfavorable factor, 3-fold increasing the risk of the transformation of olygomenorrhea or pubertal uterine bleeding into SA, is the low birth weight registered in the patient’s history.

Disruptions in the menstrual cycle are a common complaint in primary care and women's health. Irregular or absent menstrual periods should trigger an evaluation to identify the root cause. This article discusses secondary amenorrhea and provides a systematic approach to its diagnostic evaluation, with referral considerations. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a disease which can affect various organs, including human's genital organs such as the endometrium. Tuberculosis endometritis can cause clinical symptoms of secondary amenorrhea and infertility. Infertility in genital TB caused by the involvement of the endometrium. The case presentation is 33-year-old woman from dr. Saiful Anwar hospital to consult that she has not menstruated since 5 years ago (28 years old). The diagnosis was done by performing a clinical examination until the diagnosis of secondary amenorrhea due to tuberculosis endometritis is obtained. A treatment by using category I of anti-tuberculosis drugs was done for 6 months, and afterwards an Anatomical Pathology observation found no signs of the tuberculosis symptoms. Based on that, patient, who was diagnosed to have secondary amenorrhea due to tuberculosis endometritis, has no signs of tuberculosis process after being treated by using category I of anti-tuberculosis drugs for 6 months.

We examined 11 women aged 19-26 years (mean age 22.5±3.5 years) with secondary amenorrhea complaining frequent urination over 1.5 years and repeatedly, but unsuccessful treated for overactive bladder and chronic cystitis. The rare cause of sustained urination disorders in young female patients of reproductive age was established: development of secondary amenorrhea caused by weight loss ('cosmetic' amenorrhea) with subsequent estrogene deficit and urogenital atrophy. Morphological examination of the bladder mucosa, an important clue to the diagnosis, helps to identify the true cause of dysuria, urogenital atrophy of the bladder mucosa, in secondary ('cosmetic') amenorrhea, and determine future course of etiopathogenic treatment of sustained dysuria in young women. The treatment is often effective in case of proper and timely diagnosis and the absence of irreversible changes. [ABSTRACT FROM AUTHOR]

Perrault syndrome (PRLTS) is a heterogeneous group of clinical and genetic disorders characterized by sensory neuronal hearing loss in both sexes and premature ovarian failure or infertility in females. Neurological and hearing loss symptoms appear early in life, but female infertility cannot be detected before puberty. Spastic limbs, muscle weakness, delayed puberty and irregular menstrual cycles have also been observed in PRLTS patients. Mutations in five genes, i.e. HSD17B4, HARS2, CLPP, LARS2, and C10orf2, have been reported in five subtypes of PRLTS. Here, we report a milder phenotype of PRLTS in a Turkish family in which two affected patients had no neurological findings. However, both were characterized by sensory neuronal hearing loss and the female sibling had secondary amenorrhea and gonadal dysgenesis. Genome-wide homozygosity mapping using 300K single-nucleotide polymorphism microarray analysis together with iScan platform (Illumina, USA) followed by candidate gene Sanger sequencing with ABI 3500 Genetic Analyzer (Life Technologies, USA) were used for molecular diagnosis. We found a novel missense alteration c.624C>G; p.Ile208Met in exon 5 of the CLPP at chromosome 19p13.3. This study expands the mutation spectrum of CLPP pathogenicity in PRLTS type 3 phenotype. [ABSTRACT FROM AUTHOR]

Objective: Here, we present a case of ACTH-dependent pituitary macroadenoma (Cushing's disease) resulting in secondary amenorrhea mimicking polycystic ovary syndrome (PCOS). Case Report: A 20-year-old nulligravid woman had been suffering from oligomenorrhea, amenorrhea, and moderate hirsutism since the age of 18 years. She visited a gynecologic clinic where PCOS was impressed according to the clinical manifestation and ultrasound finding. The patient responded to medication in the 1st year, but gradually failed to induce menses. She was advised to visit the endocrinology department for secondary amenorrhea and endocrine survey. Physical examination revealed central obesity, supraclavicle fatpad, abdominal striae, and myopathy of four limbs. Endocrine studies revealed: serum prolactin 21 ng/mL (3.0-20 ng/mL), FSH 5.69 mIU/mL (3.4-10.0 mIU/mL), LH 1.01 mIU/mL (1.1-11.6 mIU/mL), E2 < 20 pg/mL (follicular phase 53-258 pg/mL), ACTH 110 pg/mL (0-46.0 pg/mL), cortisol 26.7 μg/dL at 8 a.m. (5.0-25 μg/dL), cortisol 21.3 μg/dL at 11 p.m. (half of normal morning value). Right pituitary macroadenoma was diagnosed through a series of dexamethasone tests and MRI. The patient received staging surgery including transsphenoidal adenomectomy and right frontotemporal craniotomy. As a result, the patient's physical condition gradually improved, and her menstrual cycle became regular with medication after the operation in the outpatient follow-up. Conclusion: PCOS is a common disease resulting in secondary amenorrhea. However, Cushing's syndrome resulting from pituitary macroadenoma should also be considered. Therefore, a careful history, observation, physical examination, and endocrine studies can differentiate between patients with PCOS and Cushing's disease.

Tuberculosis (TB) is a disease which can affect various organs, including human's genital organs such as the endometrium. Tuberculosis endometritis can cause clinical symptoms of secondary amenorrhea and infertility. Infertility in genital TB caused by the involvement of the endometrium. The case presentation is 33-year-old woman from dr. Saiful Anwar Public Hospital to consult that she has not menstruated since 5 years ago (28 years old). The diagnosis was done by performing a clinical examination until the diagnosis of secondary amenorrhea due to tuberculosis endometritis is obtained. A treatment by using category I of anti-tuberculosis drugs was done for 6 months, afterward an Anatomical Pathology observation found no signs of the tuberculosis symptoms. Based on that, patient, who was diagnosed to have secondary amenorrhea due to tuberculosis endometritis, has no signs of tuberculosis process after being treated by using category I of anti-tuberculosis drugs for 6 months. [ABSTRACT FROM AUTHOR]