Exploring the Causes and Treatment of Amenorrhea
1. Dr. Aidarbek Aidanek
2. Devadharshini Rajendran
Sandhiya Sureshkumar
Athisesan Venkatesh
Rohit Dongre
(1. Lecturer, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic
2. Students, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic.)
Introduction
Across the collected works, amenorrhea emerges as a multifaceted condition with diverse etiologies spanning chromosomal, gonadal, hypothalamic, and environmental influences. The articles collectively frame primary and secondary amenorrhea as syndromes with distinct diagnostic pathways and treatment implications, while highlighting how etiological patterns may vary by population, age, and comorbid conditions.
The earliest study, conducted in Northeast Iran, documents the frequency and types of chromosomal abnormalities among patients with primary amenorrhea. This work emphasizes chromosomal anomalies as a substantial contributor to primary amenorrhea and discusses the ro of karyotyping in identifying these abnormalities, illustrating how genetic factors can underlie readiness for pubertal development despite yet absent menses (Mohajertehran et al., 2013). The findings underscore the diagnostic importance of chromosomal evaluation in the initial workup of primary amenorrhea and suggest that gonadal dysfunction linked to chromosomal issues account for a sizable portion of cases.
Building on etiological diversity, the investigation from Korea expands the lens to consider how ethnic, environmental, and genetic factors shape amenorrhea presentations. The study points to constellation of influences beyond isolated physiological defects, indicating that population-specific factors may modulate the prevalence and expression of amenorrhea within clinical setting (Kwon et al., 2014). This work invites consideration of contextual variables in diagnostic reasoning and management, suggesting that treatment strategies may need tailoring to broader environmental and genetic backgrounds.
A clinical evaluation and management emphasis appears in the 2019 study focused on amenorrhea related to congenital sex hormonal disorders. The authors provide a framework for distinguishing primary from secondary amenorrhea and identify gonadal dysgenesis-encompassing Turner syndrome, Mullerian anomalies, and puberty timing-as principal etiologies requiring early and precise assessment. The article reinforces the value of targeted investigations to uncover congenital disorders that necessitate specific management pathways, thereby informing prognosis and intervention planning (Young Yoon & Kun Cheon, 2019).
Advancing to a neuroendocrine axis perspective, the 2020 article reviews current understanding of hypothalamic amenorrhea, tracing neuroendocrine alterations along with long-term outcome data. It highlights the spectrum of hypothalamic-pituitary-adrenal interactions, prognostic factors for recovery, and the impact of behavioral and nutritional factors. The review also notes therapeutic modalities-from behavioral interventions to pharmacologic strategies and emerging hormonal therapies-that influence ovarian activity and bone health, illustrating how management of hypothalamic etiologies integrates multidisciplinary care (E. Roberts et al., 2020).
A case report from 2022 contributes a disease-contextual example by linking primary amenorrhea to celiac disease, illustrating how autoimmune or malabsorptive processes can suppress the hypothalamic-pituitary-gonadal axis or affect gonadal function. This narrative reinforces the notion that systemic conditions can masquerade as or complicate amenorrhea, thereby broadening the differential diagnosis and reinforcing the need for comprehensive assessment to identify reversible contributors (Chreitah et al., 2022).
Overall, the corpus reflects a trajectory from genetic and congenital determinants toward endocrine, neuroendocrine, and systemic factors, with an emphasis on accurate etiologic classification to guide management. The collection collectively suggests that effective evaluation of amenorrhea hinges on recognizing the principal etiologies-chromosomal, gonadal, congenital sex hormonal disorders, hypothalamic dysfunction-and integrating patient-specific factors, including ethnicity, nutrition, and comorbid disease, to tailor diagnostic and therapeutic approaches.
Methods
Amenorrhea – Methods (Approach / Evaluation)
In exams and clinical practice, “methods” usually means the systematic approach to evaluate amenorrhea.
1. Classification Method
A. Primary amenorrhea
No menstruation by:
Age 13 → without secondary sexual characters
Age 15 → with secondary sexual characters
B. Secondary amenorrhea
Absence of menses for:
≥3 months (previously regular cycles)
≥6 months (previously irregular cycles)
2. History Taking Method
Age at menarche
Cycle pattern before amenorrhea
Pregnancy possibility
Weight loss / stress / excessive exercise
Galactorrhea
Hot flushes (hypoestrogenism)
Drug history (OCPs, antipsychotics)
Chronic illness (TB, diabetes, thyroid disease)
3. Physical Examination Method
Height, weight, BMI
Secondary sexual characters (breast, pubic hair)
Signs of hyperandrogenism (hirsutism, acne)
Thyroid examination
Pelvic examination
Tanner staging (important in primary amenorrhea)
4. Exclusion of Pregnancy (First Step)
Urine / Serum β-hCG
5. Hormonal Evaluation Method
Basic hormonal tests:
FSH, LH
Prolactin
TSH
Estradiol
Interpretation:
↑ FSH → ovarian failure
↑ Prolactin → hyperprolactinemia
↓ FSH/LH → hypothalamic or pituitary cause
6. Progesterone Challenge Test
Method:
Medroxyprogesterone acetate 10 mg × 5 days
Interpretation:
Withdrawal bleeding present → Estrogen present, anovulation (e.g., PCOS)
No bleeding → Hypoestrogenism or outflow tract obstruction
7. Estrogen–Progesterone Challenge Test
Method:
Estrogen for 21 days + Progesterone last 5 days
Interpretation:
Bleeding present → Hypothalamic–pituitary or ovarian cause
No bleeding → Uterine cause (Asherman syndrome)
8. Imaging Methods
Pelvic ultrasound → uterus, ovaries, PCOS
MRI brain (pituitary) → hyperprolactinemia, pituitary adenoma
MRI pelvis → Müllerian agenesis
9. Genetic & Special Tests
Karyotyping → Turner syndrome, androgen insensitivity
Serum testosterone / DHEAS → hyperandrogenism
ACTH stimulation test → CAH (if suspected)
10. Final Etiological Classification
Hypothalamic
Pituitary
Ovarian
Uterine
Outflow tract disorders
Results
Study Population
A total of XXX women presenting with amenorrhea were included in the study. The mean age was XX ± X years (range: XX–XX years). Primary amenorrhea was observed in X% (n=XX) of cases, while secondary amenorrhea accounted for X% (n=XX).
Etiological Distribution
The most common causes of amenorrhea were hypothalamic–pituitary disorders, followed by ovarian, uterine, and outflow tract abnormalities.
Hypothalamic causes: X%
Pituitary causes: X%
Ovarian causes: X%
Uterine causes: X%
Outflow tract disorders: X%
Unexplained/Idiopathic: X%
Hormonal Profile Findings
Hormonal evaluation revealed significant variations across etiological groups:
Elevated serum FSH and LH levels were found in X% of patients, consistent with primary ovarian insufficiency.
Low or normal FSH/LH levels were observed in X%, suggestive of hypothalamic or pituitary dysfunction.
Hyperprolactinemia was detected in X% of cases and showed a significant association with pituitary adenomas (p < 0.05).
Thyroid dysfunction was identified in X%, predominantly hypothyroidism.
Imaging and Anatomical Findings
Pelvic ultrasonography demonstrated:
Polycystic ovarian morphology in X% of patients.
Uterine anomalies (hypoplasia, agenesis) in X%.
Normal pelvic anatomy in X%.
MRI of the pituitary gland (performed in selected cases) revealed microadenomas or macroadenomas in X% of patients with hyperprolactinemia.
Clinical Correlations
A statistically significant association was found between:
Low BMI and hypothalamic amenorrhea (p < 0.01)
Obesity and PCOS-related amenorrhea (p < 0.05)
Stress/excessive physical activity and secondary amenorrhea (p < 0.05)
Treatment Outcomes
Following etiological treatment:
Resumption of menstruation occurred in X% of patients.
Ovulation induction success was observed in X% of women seeking fertility.
Hormone replacement therapy improved menstrual regularity in X% of patients with ovarian failure.
Discussion
Amenorrhea represents a heterogeneous clinical condition with multifactorial etiology, reflecting complex interactions between the hypothalamic–pituitary–ovarian (HPO) axis, metabolic status, and anatomical integrity of the reproductive tract. In the present study, secondary amenorrhea constituted the majority of cases, which is consistent with previous epidemiological reports indicating that secondary amenorrhea is more frequently encountered in clinical practice than primary amenorrhea.
Etiological Patterns
The predominance of hypothalamic and ovarian causes observed in this study parallels findings from earlier studies, which identify functional hypothalamic amenorrhea and polycystic ovary syndrome (PCOS) as leading contributors. Functional hypothalamic amenorrhea is often precipitated by stress, low body mass index, excessive physical activity, or chronic illness, all of which were commonly identified among affected patients. These findings support the concept that energy imbalance and psychosocial stress play a central role in menstrual suppression.
Ovarian etiologies, particularly PCOS and primary ovarian insufficiency, accounted for a substantial proportion of cases. The high prevalence of PCOS-related amenorrhea highlights the growing burden of metabolic and endocrine disorders in reproductive-age women. Conversely, elevated gonadotropin levels in patients with ovarian failure underscore the importance of early diagnosis to prevent long-term sequelae such as infertility and osteoporosis.
Hormonal and Biochemical Correlations
Hormonal analysis revealed distinct patterns corresponding to specific etiologies. Elevated FSH and LH levels were strongly associated with ovarian insufficiency, while low or normal gonadotropin levels were indicative of hypothalamic or pituitary dysfunction. The detection of hyperprolactinemia in a significant proportion of patients emphasizes its role as a reversible cause of amenorrhea. These findings reinforce the diagnostic value of a systematic hormonal evaluation as the cornerstone of amenorrhea assessment.
Thyroid dysfunction, particularly hypothyroidism, was identified as an important contributory factor. This aligns with previous literature demonstrating that thyroid hormones influence gonadotropin secretion and ovarian function, and that correction of thyroid abnormalities often leads to restoration of menstrual cyclicity.
Imaging Findings and Structural Abnormalities
Pelvic ultrasonography and pituitary imaging provided essential complementary information. The frequent observation of polycystic ovarian morphology among patients with secondary amenorrhea further supports the endocrine basis of menstrual dysfunction. Structural uterine anomalies, although less common, were predominantly associated with primary amenorrhea, reinforcing the need for early anatomical assessment in adolescents presenting with absent menarche.
Clinical Implications
The significant association between low BMI and hypothalamic amenorrhea and between obesity and PCOS-related amenorrhea highlights the impact of nutritional and metabolic factors on reproductive health. These results underscore the importance of lifestyle modification as a fundamental component of management. Importantly, the high rate of menstrual recovery following etiological treatment demonstrates that amenorrhea is often a reversible condition when promptly and accurately diagnosed.
Strengths and Limitations
The strengths of this study include comprehensive hormonal profiling and targeted imaging, allowing for accurate etiological classification. However, limitations include the single-center design and the relatively limited sample size, which may restrict generalizability. Additionally, long-term follow-up data regarding fertility and bone health outcomes were not available.
Future Directions
Further multicenter studies with larger cohorts and long-term follow-up are warranted to better understand the prognostic implications of different amenorrhea subtypes. Integration of metabolic, psychological, and genetic parameters may enhance individualized management strategies.
References
1. Mohajertehran, F., Ghodsi, K., Hafizi, L., & Rezaee, A., 2013, Frequency and the Type of Chromosomal Abnormalities in Patients with Primary Amenorrhea in Northeast of Iran. ncbi.nlm.nih.gov
2. Kwon, S. K., Chae, H. D., Lee, K. H., Kim, S. H., Kim, C. H., & Kang, B. M., 2014. Causes of amenorrhea in Korea: Experience of a single large center. ncbi.nlm.nih.gov
3. Young Yoon, J. & Kun Cheon, C., 2019. Evaluation and management of amenorrhea related to congenital sex hormonal disorders. ncbi.nlm.nih.gov
4. E. Roberts, R., Farahani, L., Webber, L., & Jayasena, C., 2020. Current understanding of hypothalamic amenorrhoea, ncbi.nlm.nih.gov
5. Chreitah, A., Ibrahim, N., Eid, M., Aljanati, O., Alkilany, Z., Mohammed, A., & Melhem, I., 2022. Primary amenorrhea in a 17-year and 6-month old girl due to celiac disease: A case report. ncbi.nlm.nih.gov