Pathogenetic aspects of menstrual and reproductive disorders in obese women

Efendieva R.M., Dikke G.B., Abusueva Z.A., Shilova N.V.

1) Dagestan State Medical University, Makhachkala, Russia; 2) Inozemtsev Academy of Medical Education, St. Petersburg, Russia; 3) National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), Moscow, Russia

Background: Obesity, which prevalence in Russia ranges from 24 to 36%, leads to negative consequences for reproductive health - menstrual cycle disorders (MCD) and infertility. The results of the study of the mechanisms of the obesity influence on the menstrual cycle, folliculogenesis and ovulation are still controversial.
Objective: Assessment of the metabolic, hormonal, immune, vitamin and mineral status in patients with obesity and determination of the most significant risk factors for menstrual and reproductive dysfunction.
Materials and methods: Design: a simple observational study. 70 patients were included: Group I (n=40) – with obesity and oligo-/amenorrhea-type MCD, and Group II (n=30, control) – healthy. Clinical and laboratory research methods, pelvic ultrasound and folliculometry were used.
Results: The age of the participants ranged from 20 to 37 years (mean – 27.9 (SD 3.8), p=0.99). The body mass index (BMI) in patients with obesity corresponded to stage I (32.1 kg/m2), oligomenorrhea occurred in 90% of them, amenorrhea – in 10%, heavy menstrual bleeding (HMB) in 85%, ovulation was recorded 2.5 times less frequently than in group II (35 versus 86.7%, respectively, OR 0.40, 95% CI: 0.23–0.26), and the risk of anovulation was 5 times higher, respectively (OR 4.88, 95% CI: 1.90–12.48). The profile of obese patients showed the following: insulin resistance (HOMA index – 3.1 c.u.), significant increase in the insulin (by 3 times), homocysteine ( by 2.4 times), CRP (by 6 times), leptin (by 6 times), free testosterone (by 3 times), DHEA-S (by 1.4 times), cytokines (by 6 times on average) levels, decreased levels of HDL and LH (both – by 1.5 times), folic acid (by 3 times), manganese and 25-hydroxycalciferol (by 2 times) compared to the control group. Based on the analysis of the principal components, it was established that the factor loadings of the key markers reflected a greater contribution of the metabolic factor and, to a lesser extent, the hormonal factor in the formation of anovulation in obese patients. The most significant risk factors for anovulation were insulin resistance and leptin, insulin, triglycerides, LDL levels above the reference values and HDL level below the reference values. Among the hormonal profile parameters, the key marker of anovulation was a decrease in LH levels in combination with low serum folate concentrations. The inflammatory status typical for obese patients was associated with MCD but did not affect ovulatory function.
Conclusion: In patients with stage I obesity, metabolic disorders play a leading role in the pathogenesis of MCD and anovulation, and hormonal disorders play a lesser role.

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About the Authors

Ramina M. Efendieva, Postgraduate Student, Department of Obstetrics and Gynecology, Faculty of Medicine, Dagestan State Medical University, Makhachkala, Russia; romidok@mail.ru, ORCID: https://orcid.org/0009-0002-1729-478 (corresponding author)
Galina B. Dikke, Dr. Sci. (Med.), Professor, Department of Obstetrics and Gynecology with the Course of Reproductive Medicine, Inozemtsev Academy of Medical Education, St. Petersburg, Russia; galadikke@yandex.ru, ORCID: https://orcid.org/0000-0001-9524-8962
Zukhra A. Abusueva, Dr.Sci. (Med.), Professor, Department of Obstetrics and Gynecology, Faculty of Medicine, Dagestan State Medical University, Makhachkala, Russia; zuhraabusueva@mail.ru, ORCID: https://orcid.org/0000-0002-7729-1606
Natalia V. Shilova, Cand. Sci. (Med.), Associate Professor, Department of Industrial Pharmacy, National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), Moscow, Russia; nvshilova@gmail.com, ORCID: https://orcid.org/0000-0001-6734-0147

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