Amenorrhea Research Articles

First and second-generation endometrial ablation devices: A network meta-analysis

ObjectiveFirst-generation and second-generation endometrial ablation (EA) techniques, along with medical treatment and invasive surgery, are considered successful lines of management for abnormal uterine bleeding (AUB). We set out to determine...

Anatomical and Functional Evaluation of Modified Abbe-McIndoe Vaginoplasty at a Tertiary Care Hospital.

Mayer-Rokitansky-Kuster-Hauser (MRKH) Syndrome, the second important cause of primary amenorrhea, is characterized by complete mullerian agenesis in the presence of normal karyotype and normal functioning ovaries. Incidence is one in 4500 females. Treatment options include surgical and non-surgical methods. Surgical treatment by creating a neovagina between bladder and rectum is preferred as it gives immediate results. To evaluate the anatomical and functional outcomes of modified vaginoplasty procedures conducted in our institution. An ambispective cohort study was conducted in the Department of Obstetrics and Gynaecology, at a tertiary care hospital and included 10 cases of MRKH syndrome, who underwent surgical treatment in our department. Postoperative outcome was noted. Sexual function was evaluated using the Female Sexual Function Index (FSFI) score. The mean duration of surgery was 40 minutes. The average blood loss during surgery in patients undergoing vaginoplasty was 60 ml. The mean length of the neovagina as measured 1 month after surgery was 7.9 cms. FSFI score was >30 in eight patients. Two patients were lost to follow-up. Modified McIndoe vaginoplasty is a simple, safe, and cost-effective procedure in the hands of experts. Only mature patients willing to follow the instructions and planning to get married soon should undergo this surgery.

Clinical and genetic characteristics of disorders of sex development in Sudanese patients

Given the scarce data on DSD in Sudan, we aimed to characterize DSD's clinical and genetic profile in Sudanese patients. We studied 60 patients with DSD using clinical data, cytogenetics, and PCR for the SRY gene. The results showed that 65% grew up as females and 35% as males. There was a high percentage of consanguineous parents (85%). Female genital mutilation (FGM) was performed in 75% of females. Patients who presented after pubertal age were 63%, with ambiguous genitalia in 61.7%, followed by primary amenorrhea (PA) in 30%. The SRY gene was positive in 3.3% of patients with 46,XX karyotype and negative in 6.7% of patients with 46,XY karyotype. 5αR2D-DSD was seen in 43.3%, gonadal dysgenesis in 21.7%, Ovotesticular syndrome in 6.7%, Swyer and Turner syndrome in 5% each, and Androgen Insensitivity Syndrome (AIS) in 3.3%. In conclusion, DSD in Sudan has a distinct profile with late presentation, dominated by 5αR2D-DSD due to the increased consanguineous marriage, and FGM represents a significant risk for DSD patients.

Anomalies of Sexual Differentiation in the Medicine and Endocrinology Department of the Mali Hospital - Bamako

Introduction: Abnormalities of sexual differentiation are conditions due to various congenital or hormonal etiologies. The aim of our study was to describe the clinical aspects of sexual differentiation abnormalities in the department of medicine and endocrinology. Methodology: Our study was retro-prospective and descriptive ranging from September 2011 to July 2021 (i.e. 10 years), carried out in the Medicine and Endocrinology department of the Mali Hospital. Results: Ten patients out of 8213 consultants were collected, representing a hospital frequency of 0.12%. Six (6) of them were of female phenotype, and 2 of male phenotype. The average age was 21.71 years with extremes ranging from 17 days to 46 years. Clinically, patients with a female phenotype presented an anomaly of the external genitalia (5/10), axillary and pubic hypopilosity (6/10), delayed puberty (5/10), primary amenorrhea (5/10), and the presence of a bilateral inguinal mass (2/10). For patients with a male phenotype (2/10); bilateral gynecomastia (2/10), macroskelia (1/10) with wingspan of 197cm, axillary and pubic hypopilosity (1/10), an anomaly of the external genitalia (2/10). Conclusion: anomalies of sexual differentiation, although relatively rare, exist in Mali and throughout the world.

Unusual coexistence of restrictive heart disease and Kallmann syndrome: a case report

BackgroundKallmann–Morsier syndrome is a rare disease characterized by the association of congenital gonadotropic deficiency and anosmia or hyposmia. The cardiac manifestations associated with this syndrome are little known. Through this case, we will characterize the cardiac involvement of this disease in the light of what is already described in the literature.Case presentationWe report the case of a young patient who presented with a picture of cardiac decompensation revealing restrictive heart disease. In her exploration, she was found to have primary amenorrhea, leading to the diagnosis of Kallmann syndrome. Medical treatment was optimized for the management of her cardiac decompensation as well as hormonal replacement treatment for her delayed puberty and growth.ConclusionsCardiac manifestations in Kallmann–Morsier syndrome are few reported in the literature, and restrictive heart disease is uncommon with no cases report till now. This association suggests a possible common genetic origin that should be explored in the future.

Management of Amenorrhoea (Ihtibas-al-Tamth) in Unani System of Medicine: A Review

Menstrual patterns can be an indicator of overall health and self-perception of well-being. Amenorrhoea is the absence of menses in women of reproductive agewhich may be primary or secondary. Primary amenorrhoea refers to the absence of menarche at the age of 16 and secondary amenorrhoea is the cessation of menses for at least 6 months in already cycling women. Secondary amenorrhoea is more common than primary amenorrhea. Ihtibas al-Tamth (amenorrhoea) is defined in the Unani system of medicine as the absence of monthly bleeding for more than 2 months or a decrease in the quantity of menstrual blood. The etiologies of amenorrhoea may be considered categorically as outflow tract abnormalities, primary ovarian insufficiency, hypothalamic or pituitary disorders, other endocrine gland disorders, sequelae of chronic disease, physiologic, or induced. The causes of Ihtibas al-Tamth are related to Quwwat Dafia al-Badan, Madda and Johar Khun-i-Hayd, or Ala Makhraj -i-Hayd. Su’-i-Mizaj Barid, Yabis, Harr or Harr wa Yabis, Su’-i-Mizaj Maddi or Sada can lead to Du’f al-Quwwat-i-Dafia. Abnormality in quality and quantity of Madda in Su’-i-Mizaj Maddi can also lead to ihtibas al-tamth. Amenorrhoea is not a diagnosis but a symptom indicating anatomical, genetic and neuroendocrine abnormalities. It can be determined by two different groups of causes: (a) anatomical defects of the genital organs; (b) endocrine dysfunctions. Both congenital and acquired anomalies in the structure of the uterus and vagina could produce amenorrhoea; nevertheless, in most patients, amenorrhoea is related to an ovarian malfunction. Symptoms usually associated with amenorrhoea are headache, nausea, back ache and lower abdominal pain, tiredness, and some respiratory problems. Main principle of treatment includes Tawleed-i-Dam, Tanqiya-i-Akhlat Ghaleeza, Talteef-i-Khilt, Tafteeh-i-Uruq Raham and Tahzeel if obesity is the cause. Surgical intervention if hymen is imperforated. Some regimenal therapies are also beneficial in amenorrhoea, such as Fasd-i-Safin, Hammam-i-Murattib and Hijama-i-Nariya on calf area. Some Unani drugs, which are beneficial in amenorrhoea, are Habb-i-Mudir, Safoof-i-Baboona, Kushta Faulad, and Safoof Muhazzil. In the present scenario, it is utmost important to educate the patients to live a healthy and hygienic life and to avoid those factors which cause amenorrhoea.

Magnetic resonance imaging features of complete androgen insensitivity syndrome in comparison to Mayer-Rokitansky-Küster-Hauser syndrome.

Complete androgen insensitivity syndrome (CAIS) and Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) share common clinical features such as female phenotype, vaginal hypoplasia, and primary amenorrhea. Magnetic resonance imaging (MRI) is performed to investigate the cause of primary amenorrhea. However, the MRI features are also similar in both disorders. They are ultimately diagnosed by chromosome testing, but there is a possibility of misdiagnosis if chromosome testing is not performed. This study aimed to identify MRI features that are useful for differentiating CAIS from MRKHS. This multicenter retrospective study included 12 patients with CAIS and 19 patients with MRKHS. Three radiologists blindly evaluated the following features: (1) detection of vagina, (2) detection of nodular and cystic structures in the lateral pelvis; undescended testicles and paratesticular cysts in CAIS and rudimentary uteri and ovaries in MRKHS, (3) their location, (4) number of cysts in the cystic structures, and (5) signal intensity on diffusion-weighted images (DWI) and apparent diffusion coefficient (ADC) values of the nodular structures. Statistical comparisons were performed using Mann-Whitney U and Fisher's exact tests. Compared with MRKHS, the CAIS group showed significantly detectable vagina, more ventrally located nodular and cystic structures, fewer cysts within the cystic structures, and nodular structures with higher signal intensity on DWI and lower ADC values. MRI features of detectable vagina, location of nodular and cystic structures, number of cysts within the cystic structures, signal intensity on DWI and ADC values of the nodular structures were useful in differentiating CAIS from MRKHS.

Primary Amenorrhoea

The amenorrhoea is the normal physiological feature in prepubertal girls, failure to commence menstruation is primary amenorrhea. A normal uterovaginal anatomy and functional hypothalamic pituitary ovarian (HPO) axis is essential for menstruation. The detailed relevant medical and family history along with thorough physical examination adds in for requesting relevant investigations to find out the cause. In the absence of secondary sexual characteristics, hormonal disturbances are the most likely cause while anatomical problems are more common in the presence of secondary sexual characteristics, along with physiological delays and endocrinopathies. Investigate primary amenorrhoea without secondary sexual development at 13 years and with secondary sexual development at 15 years of age, consider early referral if suspicion of chromosomal abnormality, hyperandrogenemia, anatomical abnormalities or primary amenorrhoea persists for five years after thelarche. The multidisciplinary team approach, to support patient and parents with evidence base knowledge for decision-making is the corner stone. It is important to address patient and their family needs, individually for the best outcome.

Melatonin and sexual development of adolescents with type 1 diabetes

Objective — to study the level of daily melatonin excretion in adolescents with type 1 diabetes mellitus (DM1) at the stages of puberty, taking into account the course of puberty. Materials and methods. The investigation involved 172 patients with DM1 aged 9—18 years (85 boys and 87 girls), who stayed in the Endocrinology Department of the SI «Institute for Children and Adolescents Health Care of the NAMS of Ukraine» for examinations and treatment. The DM1 duration was 1 to 10 years. With account of the level of sexual development at the time of examination, adolescents were divided into the following subgroups: prepuberty (T1); early puberty (T2); puberty itself (T3); late puberty (T4). The nature of sexual maturation was assessed with account of the norms for the corresponding age. The nature of melatonin production was assessed by the excretion of its main metabolite — 6-­sulfatoxymelatonin in daily urine, which was determined by fluorometric method. Statistical processing of the results was carried out using application packages Microsoft Excel and SPSS 17.0. Results and discussion. The effects of puberty on melatonin production have been determined, with its increase during puberty and late puberty. It has been proven that violation of the puberty course is accompanied with changes in the melatonin levels, corresponding to the degree of sexual development of girls and boys with DM1. In conditions of accelerated puberty, the melatonin level increases, and it decreases in case of slowdown sexual development. In girls of 14—18 years old, the lowest melatonin levels were determined in patients with delayed sexual development and primary amenorrhea. During sexual maturation, formation of epiphyseal­pituitary­gonadal and epiphyseal­pituitary­thyroid links takes place, their nature changes in the course puberty. Conclusions. In adolescents with DM1, the age-related dynamics of daily melatonin excretion during puberty is preserved, with an increase in its levels during late puberty. Melatonin levels in patients with DM1 depend on the sexual maturation course, and they are altered in case of its disorders. Regardless of gender, at delayed sexual development significantly lower melatonin levels were registered in comparison with patients with normal sexual development. The nature of correlations between melatonin and hormonal indicators depends on the level of an adolescent’s sexual development and gender.

Severe Asherman Syndrome: Secondary Amenorrhoea, Hysteroscopic Management Followed by Fruitful Pregnancy: A Case Report

Severe Asherman Syndrome: Secondary Amenorrhoea, Hysteroscopic Management Followed by Fruitful Pregnancy: A Case Report

Interpretation of Mayer-Rokitansky-Küster-Hauser syndrome by systematic literature review

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, also known as Müllerian aplasia, is a rare congenital anomaly affecting the female genital tract, characterized by the absence of the uterus, cervix and upper vagina in women with normal appearance, karyotype 46 XX and normal endocrine function. The aim of the study was to interpret the main risk factors, clinical criteria and diagnosis of MRKH syndrome and its psychosocial impact through a literature review. A descriptive documentary literature review was conducted, analyzing articles published between 2019 and 2023 in high-impact journals. Sixteen articles were identified, including case studies and theoretical sources of information. The syndrome was found to affect approximately 1 in 4 000 to 5 000 women, with possible genetic basis. Two types are distinguished: type I, with absence of the uterus and vagina, and type II, with additional kidney and skeletal malformations. Diagnosis is made by ultrasound and MRI, and treatment includes the creation of a neovagina through surgical or non-surgical procedures. The syndrome carries a significant emotional and psychological burden due to infertility and sexual difficulties. It was concluded that MRKH involves risk factors such as family history, primary amenorrhea and normal development, requiring a multidisciplinary approach and including treatment options. In Ecuador, the lack of protocols and awareness presents challenges for those affected. It is vital to raise awareness of this condition and support research to improve the quality of life of those affected

Exome Sequencing to Identify Novel Variants Associated with Secondary Amenorrhea and Premature Ovarian Insufficiency (POI) in Saudi Women.

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. 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. 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.

Selective peripheral tissue response to high testosterone levels in an infertile woman without virilization signs.

Total testosterone, which is peripherally converted to its biologically active form dihydrotestosterone (DHT), is the first-line hormone investigation in hyperandrogenic states and infertility in premenopausal women. Polycystic ovary syndrome (PCOS), the most common cause of hyperandrogenism and infertility in young women, is often associated with mild elevations of total testosterone. Whereas very high levels of total testosterone (>2-3 SD of normal reference), are most often associated with hyperandrogenic signs, menstrual irregularity, rapid onset of virilization, and demand a prompt investigation. Herein, we report a case of a 32-year-old woman who was referred to the endocrinology outpatient clinic due to secondary amenorrhea and extremely high testosterone levels without any virilization signs. We initially suspected pitfalls in the testosterone laboratory test. Total serum testosterone decreased after a diethyl-ether extraction procedure was done prior to the immunoassay, but testosterone levels were still elevated. An ovarian steroid-cell tumor (SCT) was then revealed, which was thereby resected. Twenty-four hours post surgery, the total testosterone level returned to normal, and a month later menstruation resumed. This case emphasizes that any discrepancy between laboratory tests and the clinical scenario deserves a rigorous evaluation to minimize misinterpretation and errors in diagnosis and therapeutic approach. Additionally, we describe a possible mechanism of disease: a selective peripheral target-tissue response to high testosterone levels that did not cause virilization but did suppress ovulation and menstruation. Total testosterone is the most clinically relevant hormone in investigating hyperandrogenic states and infertility in premenopausal women. Very high total testosterone levels in women (>2-3 SD of normal reference) are most often associated with hyperandrogenic signs, menstrual irregularities, and a rapid onset of virilization. In women with very elevated testosterone levels and the absence of clinical manifestations, laboratory interference should be suspected, and diethyl ether extraction is a useful technique when other methods fail to detect it. Ovarian steroid cell tumors (SCT) encompass a rare subgroup of sex cord-stromal tumors and usually secrete androgen hormones. SCTs are clinically malignant in 25-43% of cases. A selective response of peripheral target tissues to testosterone levels, with clinical manifestations in some tissues and no expression in others, may reflect differences in the conformation of tumor-produced testosterone molecules.

123. Suspected MRKH in the setting of primary amenorrhea and VACTERL

123. Suspected MRKH in the setting of primary amenorrhea and VACTERL

119. Sclerosing Stromal Ovarian Tumors: A Rare Cause of Primary Amenorrhea and Hyperandrogenism in Adolescents

119. Sclerosing Stromal Ovarian Tumors: A Rare Cause of Primary Amenorrhea and Hyperandrogenism in Adolescents

12. Recharacterizing Primary Amenorrhea in a Large Diverse Cohort

12. Recharacterizing Primary Amenorrhea in a Large Diverse Cohort

A RARE CASE OF OVARIAN AGENESIS AND HYPOPLASTIC UTERUS IN A PREPUBERTALGIRL WITH NORMAL 46, XX KARYOTYPE

Delayed onset of puberty and primary amenorrhea pose diagnostic challenges, often associated with diverse etiologies including hypothalamic-pituitary disorders, gonadal dysgenesis, and müllerian duct malformations.Historically, such syndromes have been associated with XY chromosomal components, but rare cases in karyotypically normal females (46, XX) have been reported. Comparisons with similar cases, including atypical forms of Mayer-Rokitansky-Küster-Hauser (MRKH) syndromeare made, highlighting the rarity of this condition. Despite advancements, the genetic basis remains unspecified, underscoring the need for further research. We present a unique case of gonadal agenesis and hypoplastic uterus in a 46,XX individual, without associated organ system anomalies, contributing to primary amenorrhea. Diagnostic evaluations including hormonal assessment, and pelvic MRI confirmed the absence of ovaries and severe hypoplasia of paramesonephric duct (PMND) derivatives. Treatment with 17beta estradiol successfully induced puberty, highlighting the clinical importance of timely intervention. Early detection of such cases is crucial for providing comprehensive support and improving patient outcomes.

Cervical atresia and an obliterated upper vagina presenting as primary amenorrhea

Cervical atresia and an obliterated upper vagina presenting as primary amenorrhea

Prolactinoma Presenting with Secondary Amenorrhoea in a Young Girl

Prolactinoma is the most common secreting pituitary adenoma. It has different clinical presentation in men and women which varies with age. Young women present with menstrual problems, infertility and galactorrhoea, whilst older women and men may present with loss of libido, visual disturbances and in late cases, ith osteoporosis. In approaching a young woman with secondary amenorrhoea, other cuses such as pregnancy, functional hypothalamic amenorrhea, pituitary adenoma, Polycystic Ovarian Syndrome (PCOS) or primary ovarian insufficiency should be ruled out. Prolactinoma can be confirmed in the presence of high serum prolactin level and adenoma on pituitary gland magnetic resonance imaging (MRI). Dopaminergic agonist, cabergoline is efficacious in restoring gonadal and sexual functions by normalising prolactin levels. We presented a case report onan 18-year-old girl who presented with secondary amenorrhoea for six months. On further evaluation she was noted to have galactorrhoea with substantially high prolactin level of 466.9 ng/mL (normal range: 4.0- 23) and the MRI showed a pituitary tumour measuring 1.2 x 1.1 x 1.4 cm. A diagnosis of macroprolactinoma was made and she was managed with cabergoline with gradual dose increment. At 6 months of treatment, her menstrual cycle and serum prolactin had normalised. A repeat MRI pituitary one year later showed reduction in tumour size.

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

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