High prevalence of insulin resistance, obesity and dyslipidemia in PCOS patients: IJOGR

According to research, about 5% to 10% of women aged 18 to 44 are affected by PCOS, so it is very common in endocrine among women of childbearing age. Women with symptoms of obesity, acne, amenorrhea, growing hair loss, and infertility are often diagnosed with PCOS. Women with PCOS have higher rates of endometrial cancer, heart disease, dyslipidemia, and type 2 diabetes mellitus.

Gupta and Yadav carried out a study of status of fasting serum insulin and lipid profile in PCOS patients and to determine correlation between BMI and HOMA index in PCOS patients.

Aims and Objectives of the study included:

1. To evaluate the status of serum lipid, insulin levels in patients of PCOS in M.Y. Hospital, Indore.
2. To find out the correlation between the mathematical index of insulin resistance and BMI in PCOS.

Study was done at Department of Obstetrics and Gynaecology, MGM Medical College and M. Y. Hospital, Indore (M.P). Sample Size included 100 patients with study duration 18 months. It was a Cross-sectional study that included subjects with a diagnosed case of PCOS.

PCOS can be defined as a disease in which several genetic and environmental factors determine physiological, therapeutic, and biological changes. Although the genetic etiology of PCOS remains unknown, family history of PCOS is common; however, family communication with PCOS is unclear. The natural factors involved in PCOS (e.g. obesity) can be exacerbated by poor dietary choices and physical inactivity; infectious and toxic substances can also play a role. The reproductive and physiological features of PCOS are sometimes reversed by lifestyle changes such as weight loss and exercise.

The pathophysiology of PCOS includes impairment in the autotrophic-pituitary axis, alterations in insulin secretion and function, and ovarian function. Although the cause of PCOS is unknown, PCOS is also associated with insulin resistance and obesity.

Insulin helps regulate ovarian function, and the ovaries respond to elevated levels of insulin by producing androgens, which can lead to ovarian cancer.

Clinical symptoms of PCOS include an increase in luteinizing hormone (LH) and gonadotropin-releasing hormone (GnRH), as well as untreated follicular-stimulating hormone (FSH) levels. As a result of the increase in GnRH, stimulation of ovarian thecal cells leads to increased production of androgens. Subsequent confinement can be enhanced by providing exogenous FSH.

Obesity is a common complication of PCOS but does not need to be diagnosed. PCOS presents as a phenotype indicating a vicious cycle of neuroendocrine, metabolic, and ovarian dysfunction. PCOS shows the interaction between many proteins and genes influenced by epigenetic and environmental factors. Clinical and chemical hyperandrogenism are important features of PCOS.

Ovary, adrenal, and androgen excess

PCOS is characterized by increased levels of ovarian closure and/or adrenal androgen. Internal ovarian factors such as altered steroid production and extracellular factors such as hyperinsulinemia lead to increased ovarian androgen production. Feature factors include more growing follicles in women with PCOS compared with normal controls with the premature binding of antral follicles at 5 to 8 mm.

Neuroendocrine traits

Increased LH pulse frequency, LH pulse amplitude, and increased LH / FSH ratios are found in women with PCOS. The first features of PCOS occur during the first years of adolescence, with the activation of the hypothalamic GnRH pulse generator, the increase in gonadotropin, and the increase in ovarian estrogen production.

Loci identified in the genome-wide association (GWASs) study included LHCGR, FSHR, and FSH-β polypeptide (FSHB) genes, suggesting neuroendocrine involvement in PCOS pathophysiology.

Valproate and HPO Axis function

Valproic acid (VPA), a fatty chain-fatty acid derived from valeric acid, is used to treat epilepsy, bipolar disorder, and to prevent migraine headaches. VPA raises GABA levels by interfering with the reduction of GABA. GnRH neurons express both GABAA and GABAB receptors, signaling the involvement of GABA signaling in GnRH secretion. Signing with the GABAA receptor can produce an exciting response to GnRH neurons.

Women treated with VPA may have symptoms similar to PCOS. Lean women with PCOS had a much higher concentration of CSF GABA compared to dependent female dependent women; women with PCOS also showed an increase in LH pulse amplitude and LH pulse frequency in normal blood sampling. This clinical support suggests that GABA signaling may influence neuroendocrine changes associated with PCOS such as LH pulse frequency

Insulin resistance, hyperinsulinemia

Women with PCOS have an internal IR with more independence and levels of androgen concentration. Women who are more dependent on PCOS show an increase in body mass index (BMI) leading to IR. Normal-weight girls with PCOS-weight have IR peripheral, increased liver fat, and mitochondrial muscle dysfunction compared to normal-weight girls.

Clinical Implementation

PCOS is a hormonal disease that leads to various diseases. It is a common cause of infertility among women. Although symptoms and signs vary, the three most common factors associated with PCOS include abnormal ovulation, elevated androgen levels, and multiple cysts in the ovaries. High androgen levels occur in most women with PCOS. Hirsutism, acne, and alopecia are directly related to increased androgen levels, and the prevalence of polycystic ovarian morphology in pelvic ultrasound is found in 70% of patients with PCOS.

Signs and symptoms of polycystic ovary syndrome

1. Enlarged ovaries with numerous small cysts

2. Irregular menstrual cycles

3. Pelvic pain

4. Hirsutism

5. Alopecia

6. Acne

7. Acanthosis nigricans

8. Skin tags

In this study, 24% of PCOS patients were obese. The body mass index between two groups of patients with polycystic ovary syndrome and the control group had a significant difference. There was a statistically significant association between high serum total cholesterol and low HDL with polycystic ovary syndrome. Also, the mean of serum lipid levels in the case and control groups were significantly different.

In overnight fasting, triglycerides and cholesterol were also higher in cases than in the control group. The prevalence of high triglyceride and low HDL in the case group was more than control. The cutoff for HOMAIR was taken 3.8 and 92% of PCOS patients had IR.

The present study was conducted to assess the importance of insulin resistance and derangement of lipid profile in PCOS patients. From the observation of the study, authors concluded:

1. There was a statistically significant (p value <0.005) increase in BMI of cases in comparison to controls
2. In the majority of PCOS patients HOMA index for insulin resistance was found to be on the higher side (92%), which is statistically significant(p value<0.0001).
3. 64% cases had high triglycerides levels (>160mg/dl) which is statistically significant (p value<0.0001).
4. 82% cases had low HDL levels (<50mg/dl) which is statistically significant(p value><50mg/dl) which is statistically significant (p value<0.0001).
5. Among all 24% had high BMI and 44% had borderline BMI (p value<0.0001) It shows that there is a correlation between the increased occurrence of Insulin resistance in PCOS patients with high BMI.
6. It was also found that there is significant derangement of LDL, VLDL, and serum cholesterol levels in PCOS patients (p value<0.0001) which is statistically significant.
7. It shows that patients with a family history of hypertriglyceridemia are at high risk for the development of PCOS and its complications.

Source: Gupta and Yadav / Indian Journal of Obstetrics and Gynecology Research 2021;8(3):305–309

https://doi.org/10.18231/j.ijogr.2021.065