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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.

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.

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.

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 (

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.

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: 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.

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.

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.

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.

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.

OBJECTIVE: To evaluate clinically, and with laboratory, tests, women with polycystic ovary syndrome (PCO). PATIENTS: One hundred and twelve women with PCO were studied. METHODS: The following data was recorded: Current age; age at menarche; menstrual irregularity, occurrence of similar cases in the family; fertility, obstetric history; body mass index (BMI); and presence of hirsutism. Serum measurements of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, free testosterone, and dehydroepiandrosterone sulfate were taken. RESULTS: All patients presented either oligomenorrhea (31 percent), periods of secondary amenorrhea (9 percent), or both alterations (60 percent). The majority of the patients were infertile (75.6 percent). The LH/FSH ratio was higher than 2:1 in 55 percent of the patients and higher than 3:1 in 26.2 percent. The ultrasonographic aspect of the ovaries was considered to be normal in 31 percent. CONCLUSION: The main clinical feature of the PCO is the irregularity of menses since menarche, and that the laboratory tests would be important to exclude other disorders such as hyperprolactinemia or hyperandrogenemia caused by late-onset congenital adrenal hyperplasia.