Amenorrhea Research Articles

True hermaphroditism: A nightmare for an adult

Abstract The disorder of sex development is a rare disorder that usually occurs in early childhood. As adults, those with disorder of sexual development present with gynecomastia, primary amenorrhea, and primary infertility, which often causes great psychological impact. We report a unique case of a male adult hermaphrodite presenting with hematometra and hematosalpinx. Early management including psychiatry counseling, gender reassignment, and surgery is essential. Our patient underwent müllerian tissue removal with phallus reconstruction.

Seminoma in 46, XY Gonadal Dysgenesis: Rare Presentation and Review of the Literature.

Swyer syndrome is a rare congenital condition that serves as a risk factor for developing germ cell tumors. The condition belongs to the group of 46, XY Disorders of Sexual Development (DSD) is characterized by complete gonadal dysgenesis and is mostly manifested as delayed puberty and primary amenorrhea during adolescence. Individuals with Swyer syndrome are known to be phenotypically female with normal internal and external female genitalia at birth. 46, XY gonadal dysgenesis involves a high risk of gonadoblastoma development with malignant potential such that the onset is greatest at or after the event of puberty. This report of a 12-year-old phenotypic female with 46, XY gonadal dysgenesis, who developed an advanced metastatic seminoma, aims to emphasize the rarity of the development of a seminoma in the context of 46, XY CGD.

A RARE CAUSE OF HYPOPITUITARISM - SHEEHAN SYNDROME

Sheehan syndrome is a rare complication of post-partum hemorrhage causing post-partum ischemic necrosis of the pituitary gland. It is a disease with declining incidence, more prevalent in developing countries. The incidence of Sheehan syndrome is 1 in 100,000 births. It was first described by a British pathologist Harold Leeming Sheehan in 1937.We present the case of a 42 year old female who presented with bilateral knee pain for 4 years, on over-the-counter steroids. She gave a history of lactational failure and secondary amenorrhea following childbirth. Her investigations revealed central hypothyroidism and she was diagnosed as Sheehan syndrome.

Magnetic resonance imaging in patients of Mayer–Rokitansky–Kuster–Hauser (MRKH) syndrome presenting with primary amenorrhoea: a prospective study

BackgroundThis study aims to characterize the spectrum of imaging findings in patients of Mayer–Rokitansky–Kuster–Hauser (MRKH) syndrome presenting with primary amenorrhoea.Objectives(1) To aid in clinical diagnosis of MRKH syndrome. (2) To detect the associated non gynecological anomalies. (3) To arrive at optimal management options.ResultsThis prospective observational study was performed in 14 subjects who presented with primary amenorrhoea and diagnosed as MRKH on MRI from 1st January, 2021 to 30 June, 2022. Out of 14 patients, 4 patients showed hypoplastic uterus while remaining 10 showed complete uterine agenesis. Mean volume of hypoplastic uterus was 5.3 ml. Out of 10 patients with complete uterine agenesis, 9 showed bilateral rudimentary uterine buds connected by a fibrous band while 1 showed unilateral bud. 3 uterine buds showed three layered zonal differentiation of which 2 showed blood within lumen suggesting functioning endometrium. 1 uterine bud was located outside pelvis. Bilateral ovaries were noted in all 14 patients of which 4 ovaries were located outside pelvis and 1 ovary showed endometrioma within. 10 patients showed complete agenesis of proximal 2/3rd of vagina. Among non-gynecological findings, 2 showed unilateral renal agenesis and 1 showed unilateral hypoplastic kidney. 1 patient showed dorsal dermal sinus.ConclusionsThe findings in MRKH patients varies from complete uterine agenesis with rudimentary uterine buds or normal positioned hypoplastic uterus. The uterine buds can be functional with collection within endometrium and could lead to endometrioma formation due to retrograde menstruation. Ovaries and uterine buds can have an extra-pelvic location.

Age and menstrual cycle may be important in establishing pregnancy in female athletes after retirement from competition

ABSTRACT Background Although it has been shown that amenorrhea associated with low energy availability or relative energy deficiency in sport affects body physiology in female athletes, the association between menstrual dysfunction during active sports careers and reproductive function after retirement is not clear. Objective To investigate the association between menstrual dysfunction during their active sports career and post-retirement infertility in female athletes. Methods A voluntary web-based survey was aimed at former female athletes who had become pregnant and gave birth to their first child after retirement. Nine multiple-choice questions were included, on maternal age, competition levels and menstrual cycles during active sports careers, time from retirement to pregnancy, the time of resumption of spontaneous menstruation after retirement, conception method, and mode of delivery, etc. Regarding cases of primary and secondary amenorrhea among the abnormal menstrual cycle group, only those whose spontaneous menstruation had not recovered from retirement to the time of pregnancy were included in the study. The association between the presence of abnormal menstrual cycles from active sports careers to post-retirement pregnancy and the implementation of infertility treatment was evaluated. Results The study population included 613 female athletes who became pregnant and gave birth to their first child after retiring from competitive sports. Of the 613 former athletes, the infertility treatment rate was 11.9%. The rate of infertility treatment was significantly higher in athletes with abnormal than normal menstrual cycles (17.1% vs. 10.2%, p = 0.0225). Multivariable logistic regression analysis showed that maternal age (adjusted odds ratio [OR] 1.194; 95% confidence interval [CI] 1.129, 1.262) and abnormal menstrual cycles (OR and 1.903; adjusted OR 1.105, 3.278) were the relevant factors for infertility treatment. Conclusion It was suggested that menstrual dysfunction that persist from active sports careers to post-retirement may be a factor in infertility when trying to conceive after retirement.

Calcipenic Rickets Accompanied by Hypercoagulability, Hypokalemia and a History of Secondary Amenorrhea: A Case Report

mineralization. This case report aims to present a patient with calcipenic rickets, which are accompanied by hypercoagulability, hypokalemia, and secondary amenorrhea. In this case, a woman, 21 years old, unmarried, living outside the city of Palembang, came to the endocrine polyclinic with complaints of leg pain, making it difficult to walk along with growth retardation. In addition, there is a lump on the right arm and left knee that does not enlarge, height and weight do not increase, and both legs are bent. Based on physical examination, the general condition looked moderately ill, with vital signs within normal limits, body weight 26 kg, height 123 cm, and body mass index 17.8 kg/cm2. In the superior extremity, a 2-3 cm mass was found in the right humerus. In the lower extremities, there was a mass measuring 3 cm in the left lateral genu, supple and easy to move, with no pain. On examination of genital maturity, Tanner 2 was found. Laboratory evaluation results at the first visit to the endocrine clinic showed increased fibrinogen, d-dimer level, parathyroid hormone, and alkaline phosphatase. In addition, there was a decrease in calcium, potassium, vitamin D-25 OH, phosphorus, growth hormone, and anti-Mullerian hormone. Bone age examination shows bone age according to girls aged 15 years. The patient was diagnosed with calcigenic type rickets with hypercoagulability, hypokalemia, and secondary amenorrhea. Initial management is given calcium 500-4000 g/day, potassium 40-100 mEq/24 hours, warfarin 2 mg/24 hours, acetylsalicylic acid 80 mg/24 hours, vitamin D 1000 mg/24 hours, CaCO3 500 mg/8 hours, potassium chloride 600 mg/12 hours. In conclusion, cases of rickets are quite rare and require further examination to establish a diagnosis.

Hormono-metabolic disorders in women with hypothalamic syndrome in the ontogenetic aspect

Introduction. The rising incidence of obesity among children and adolescents has become a major public health problem. Problems of female reproductive function associated with obesity include menstrual irregularities, complications of pregnancy and childbirth, and infertility.Aim. To conduct a prospective analysis of carbohydrate, lipid metabolism, neuroendocrine regulation in women with primary infertility and hypothalamic syndrome of puberty.Materials and methods. Prospective, longitudinal study of adolescent girls (n=170) with hypothalamic dysfunction for 14.2±1.6 years, mean age was 14.41±0.26 years. The second stage of the study included an assessment of the hormonal status and metabolic changes in 86 women, of which 46 were fertile, 26 had primary infertility and 14 had secondary infertility, mean age was 21.89±1.15 years. Clinical and laboratory methods were used to study the indicators of lipid and carbohydrate metabolism, pituitary-ovarian and adrenal hormonal regulation systems, instrumental and functional research methods, as well as statistical analysis methods were carried out.Results. Among adolescent girls with hypothalamic dysfunction a high proportion of secondary amenorrhea − 31% (p=0.042) and metabolic syndrome − 86% was revealed, as well as a significant increase in follicle-stimulating hormone, testosterone, cortisol and a decrease in the concentration of progesterone, inhibin B, an increase in cholesterol, low density lipoproteins, triglycerides, the HOMA index, insulin and a decrease in high density lipoprotein cholesterol. We found a high proportion of polycystic ovary syndrome − 19.8%, polymenorrhea − 18.6%, oligomenorrhea − 19.8%, primary infertility − 30.2%, (p=0.001) in women with a history of hypothalamic obesity in the pubertal period. We determined a set of primary infertility predictors: the presence of triglyceridemia and hyperlipidemia in the puberty period (OR 9.5; 95%CI [1.7–51.9]) and hormone-dependent diseases in the reproductive period (OR 5.6; 95%CI [2.5–18.2]).Conclusion. In our opinion, timely prevention and correction of lipid metabolism disorders in adolescents, as well as early detection of hormone-dependent diseases in the reproductive period are promising for the prevention of reproductive disorders.

Diagnosis of 17-alpha hydroxylase deficiency performed late in life in a patient with a 46,XY karyotype.

17-Alpha-hydroxylase deficiency (17OHD) is a rare autosomal recessive disease, representing 1% of cases of congenital adrenal hyperplasia. A 44-year-old female presented to the emergency department complaining of generalized asthenia and polyarthralgia for about 2 weeks. On examination, she was hypertensive (174/100 mmHg), and laboratory results revealed hypokalemia and hypocortisolism. She had an uncharacteristic morphotype, BMI of 16.7 kg/m2, cutaneous hyperpigmentation, and Tanner stage M1P1, with normal female external genitalia. She reported to have primary amenorrhea. Further analytical evaluations of her hormone levels were performed CT scan revealed adrenal bilateral hyperplasia and absence of female internal genitalia. A nodular lesion was observed in the left inguinal canal with 25 × 10 mm, compatible with a testicular remnant. Genetic analysis identified the c.3G>A p.(Met1?) variant in homozygosity in the CYP17A1 gene, classified as pathogenic, confirming the diagnosis of 17OHD. Karyotype analysis was compatible with 46,XY. The association of severe hypokalemia, hypertension, hypocortisolism, and oligo/amenorrhea and the absence of secondary sexual characteristics favored the diagnosis of 17OHD, confirmed by genetic testing. As in other published clinical cases, diagnosis outside pediatric age is not rare and should be considered when severe hypokalemia occurs in hypertensive adults with a lack of secondary sexual characteristics. The association of severe hypokalemia, hypertension, hypocortisolism, and oligo/amenorrhea and the absence of secondary sexual characteristics favor the diagnosis of 17-alpha-hydroxylase deficiency (17OHD). Diagnosis outside pediatric age is not rare. 17OHD should be considered when severe hypokalemia occurs in hypertensive adults with a lack of secondary sexual characteristics.

Prenatal Diagnosis and Fetal Sonographic Features of Swyer Syndrome

AbstractSwyer syndrome, also known as complete gonadal dysgenesis, is characterized by an individual who has an XY karyotype but is phenotypically female. It is typically diagnosed in adolescence after investigations for primary amenorrhea. The estimated prevalence is 1 in 20,000 to 80,000 births. Mutations in the DNA-binding region of the SRY gene account for approximately 15 to 20% of cases, with the remaining cases caused by other gene mutations. There are no reports of the established diagnosis of Swyer syndrome prenatally, or of the sonographic features that may be associated with it. This report outlines the details of a 33-year-old primigravida in whom a fetal cystic hygroma was noted on ultrasound at 12 weeks gestation. Chorionic villous sampling revealed a diagnosis of fetal Swyer syndrome. The fetus progressed to develop severe fetal hydrops and a parental decision for termination of pregnancy was made at 15 weeks of gestation.

Congenital adrenal hyperplasia in adolescence - a gynecological perspective.

Analysis of congenital adrenal hyperplasia (CAH) cases, gynaecological implications, referral reasons to gynaecologist and treatment. Retrospective, longitudinal, single-centre study with female CAH paediatric patients ≥ 10 years-old, followed between 1998-2018 in gynaecology and endocrinology departments at a public university tertiary hospital. 47 patients, 34.0% (n = 16) with classic, 66.0% (n = 31) with non-classic forms (NCAH), CYP21 deficit and 46,XX karyotype. We found a normal median menarche age (11.5 IQR 2 [6-15] years-old), but significantly earlier in NCAH (p = 0.003). Precocious puberty occurred in 48.9%, n = 23. Primary amenorrhea occurred in salt-wasting form (21.4%, n = 3). Oligomenorrhea and hirsutism were significantly more prevalent in NCAH (p = 0.018, p = 0.014 respectively) and acanthosis nigricans and virilization signs in classic forms (p = 0.05, p = 0.000 respectively). Sixteen patients (34.0%) were referred to gynaecology, mostly due to menstrual irregularities (50.0%, n = 8). Medical treatment with isolated or combined corticoids, oestrogen and progestogen were chosen in all but one case. Gonadotropin-releasing hormone analogues were used in 19.0% (n = 9). Surgery was performed in 34.0% (n = 16) patients, median age 2.0 IQR 2.5 (0.6-90) years-old. This paper highlights the importance of a multidisciplinary approach. Early treatment contributes to a phenotypical feminine differentiation and normalization of the hypothalamus-pituitary-ovarian axis, which is essential given the gynaecologic and obstetric consequences of untreated cases.

Thalassemia care in Nepal: In dire need of improvement.

Thalassemia care in Nepal: In dire need of improvement.

Sheehan's syndrome misdiagnosed as encephalitis: A case report and literature review

AbstractA 48‐year‐old female patient was hospitalized for 5 days after a cold. Encephalitis was considered after preliminary history and routine examination, but the patient did not show significant improvement after antiviral treatment. At this time, magnetic resonance imaging indicated pituitary atrophy, and the patient's medical history was assessed. She had a history of postpartum bleeding and amenorrhea 15 years ago. The supplementary examination indicated hormonal abnormalities. These suggested that the patient may have had Sheehan's syndrome (SS). After hormone supplementation treatment for 10 days, her condition improved. This case suggested that in female patients with neuropsychiatric disorders with a history of previous postpartum hemorrhage, attention needs to be paid to screening for SS to improve the related diagnosis and treatment rate.

Primary amenorrhea - where is the issue? A systematic review of literature in search of an answer

Introduction and purpose: Primary amenorrhea is not a common problem, but it is a cause for concern to the people who are affected by it as well as for their guardians. There are many factors which lead to this particular condition. Making an accurate diagnosis is pivotal in order to provide the patient with correct professional treatment and restore their health. Aim of the study: Systematic review of the existing evidence on most common reasons which lead to primary amenorrhea. Brief description of the state of knowledge: Primary amenorrhea is a medical state, defined as a deficiency of primary menstrual bleeding in girls during their adolescence. Primary amenorrhea is diagnosed by meeting the criteria: no period by the age of 14 in the absence of growth or development of secondary sexual characteristics, or no period by the age of 16 regardless of the presence of normal growth and development with the appearance of secondary sex characteristics. There are multiple causes of this condition. Searching for a solution is heavily dependent on additional symptoms. Lack of menarche can be caused by anatomical anomalies of the female genital system, ovaries dysplasia, dysfunction of hypothalamus and pituitary gland, as well as by medical circumstances which are not included in those groups. Summary: The important thing is to make the proper diagnosis of primary amenorrhea. Menstruation disorders are not only gynecological problems, they can also cause systemic, psychological and sexual difficulties. It might impact the future life of maturing young girls.

CLPP inhibition triggers apoptosis in human ovarian granulosa cells via COX5A abnormality-Mediated mitochondrial dysfunction.

Premature ovarian insufficiency (POI) is characterized by early loss of ovarian function before the age of 40years. It is confirmed to have a strong and indispensable genetic component. Caseinolytic mitochondrial matrix peptidase proteolytic subunit (CLPP) is a key inducer of mitochondrial protein quality control for the clearance of misfolded or damaged proteins, which is necessary to maintain mitochondrial function. Previous findings have shown that the variation in CLPP is closely related to the occurrence of POI, which is consistent with our findings. This study identified a novel CLPP missense variant (c.628G > A) in a woman with POI who presented with secondary amenorrhea, ovarian dysfunction, and primary infertility. The variant was located in exon 5 and resulted in a change from alanine to threonine (p.Ala210Thr). Importantly, Clpp was mainly localized in the cytoplasm of mouse ovarian granulosa cells and oocytes, and was relatively highly expressed in granulosa cells. Moreover, the overexpression of c.628G > A variant in human ovarian granulosa cells decreased the proliferative capacity. Functional experiments revealed that the inhibition of CLPP decreased the content and activity of oxidative respiratory chain complex IV by affecting the degradation of aggregated or misfolded COX5A, leading to the accumulation of reactive oxygen species and reduction of mitochondrial membrane potential, ultimately activating the intrinsic apoptotic pathways. The present study demonstrated that CLPP affected the apoptosis of granulosa cells, which might be one of the mechanisms by which CLPP aberrations led to the development of POI.

AMH producing purely cystic virilizing adult granulosa cell tumor in 17 years old girl: a case report and review of literatures

BackgroundAndrogen-producing granulosa cell tumor in adolescent girl is rare condition and clinical characteristics are not fully elucidated.Case presentationSeventeen years old girl complained of secondary amenorrhea was referred to our out-patient consultation. Markedly elevated serum testosterone, LH, and AMH levels were noted. Mild hirsutism and clitoromegaly were presented. Transabdominal ultrasonography and MRI revealed cystic mass occupied pelvic cavity probably originated from left ovary. Right ovary showed polycystic appearance. Laparoscopic left ovarian cystectomy was performed. After the surgery, her menstruation resumed along with normalized hormonal parameters, and clinical hyperandrogenism were improved. Since the scarcity of cellular lining of inner cyst wall, definitive pathological diagnosis was difficult. After the consultation with gynecological pathologist, the tumor was diagnosed as sex cord stromal tumor, highly suspicious for adult granulosa cell tumor. Residual left salpingo-oophorectomy was performed by additional laparoscopic surgery. Her serum testosterone and AMH levels were remained low with regular menstrual cycles and no evidence of recurrence.ConclusionsAndrogen-producing cystic granulosa cell tumor is rare gynecological disorders, which need both gynecologic oncological and endocrinological approach. Its clinical manifestations may bring some clues to the pathogenesis of ovulatory dysfunctions, such as polycystic ovary syndrome.

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

BackgroundOld 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 presentationWe 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.ConclusionLaparoscopic cervico-isthmic anastomosis could reconstruct the uterine outflow tract successfully, alleviate symptoms, and achieve a good short-term outcome.

ANALYSIS OF THE COURSE OF PREGNANCY, CHILDBIRTH AND THE STATUS OF NEWBORNS BORN BY DISPLACED WOMEN

Aim of the study: to analyse the effect of involuntary migration on the course of pregnancy, labour and delivery, and neonatal outcomes in pregnant women in the third generation. Materials and methods. This paper presents an analysis of a prospective study of the course of pregnancy, childbirth, and the condition of new-born infants born by displaced Azerbaijani women. A prospective analysis was made in the course of puberty and the state of reproductive health in 54 refugee women of early reproductive age, who were divided into two groups, aged 18-25 and 26-35 years. Results. A study conducted among third generation women revealed pronounced negative trends in both somatic and reproductive health among refugee women in this group. Their average age ranged from 18 to 35. Most of the patients, 37 (68.5%), were born with a birth weight of less than 3000g. The mean age of parents at the time of girl's birth was 25.4±2.26 years for mothers, 26.9±5.29 years for fathers, i.e., in the immediate post-stress period. The subjects are characterized by menstrual cycle dysfunction (63%-29.5%). Hypermenorrhoea occurs in 46% of the subjects, primary amenorrhoea in 8.2%, and secondary amenorrhoea in 3.3%. There is also a high percentage of inflammatory diseases of the female genital organs (93.4%). A high percentage of somatic pathologies is found in the female patients: iron deficiency anaemia - 77.8%, gastrointestinal diseases - 48.1%, thyroid diseases - 9.3%, urinary diseases - 22.5%, helminthiasis - 16.7%, etc. Sexually transmitted infections were diagnosed in chronic form in 14 patients. The rate of placental insufficiency of grade 1a and 1b was diagnosed in 29%-16%, and delayed foetal development of grade 1 and 2 in 12%-8% respectively. Asphyxia (27%), newborn hypotrophy (7.5%), prematurity (18%) is characteristic of the newborns of this group of patients. Conclusion. Analysis of the results of a comprehensive study of the health of pregnant refugee women has shown that even in the third generation the stress associated with forced migration of the older generation and adverse socio-medical problems are reflected in the formation and functioning of the reproductive age of the younger generation.

Secondary amenorrhoea with absent axillary hair

Secondary amenorrhoea with absent axillary hair

100. Updated Causes of Primary Amenorrhea

100. Updated Causes of Primary Amenorrhea

Mixed gonadal dysgenesis, differencial diagnosis of primary amenorrhoea

Mixed gonadal dysgenesis, differencial diagnosis of primary amenorrhoea