Abstract

Introduction: Anovulation presents a variety of clinical problems like amenorrhea, irregular menses and hirsutism. When anovulation and android obesity are present, hyperinsulinemia may be an underlying disorder in most of cases. Aims and Objectives: To study the markers of insulin resistance (IR) in women with chronic anovulation, which are waist-hip ratio (WHR), fasting plasma insulin (FPI) and fasting plasma glucose/Fasting plasma insulin (FPG/FPI). Material and methods: The present study was conducted in Dept. of Obstetrics and Gynecology, LLRM Medical College, Meerut from Nov. 2003 to Oct. 2004. Total 37 cases of anovulatory bleeding on the basis of history and clinical examination were included in the study and they were examined for following parameters: Body mass index (BMI) (kg/m²), waist circumference (WC), WHR, FPG/FPI (>4.8 = IR). The tests applied to see the distribution and significance were binomial, Chi-square, fisher’s exact test. Observations and results: Out of
37 patients with chronic anovulation, 28(75.5%) had WHR >0.85 (android obesity), 23(62.2%) had fasting hyperinsulinemia and only 11 (29.11%) patients had IR. All the patients of IR, had android obesity; 90.9% of patients with IR had fasting hyperinsulinemia. Conclusion: Thus, it can be concluded that there is strong association of android obesity and chronic anovulalion and these patients are at risk of  type 2 diabetes mellitus.

Keywords: Chronic anovulation, hyperinsulinemia, waist circumference, hip circumference, waist-hip ratio

In the present scenario, anovulation is very common problem. It presents with a variety of clinical manifestation including amenorrhea, irregular menses, hirsutism. Normal ovulation requires coordination of the menstrual system at all levels:

• The central hypothalamo-pituitary axis.
• The feedback signals.
• Focal response within ovary.

Obese anovulatory women have a characteristic distribution of body fat known as android obesity, which refers to fat located in the abdominal wall and visceral mesentric location. This fat distribution is associated with hyperinsulinemia, impaired glucose tolerance (IGT), diabetes mellitus and increased androgen production rates, decrease sex hormone-binding globulin (SHBG), increased free testosterone and estradiol levels. Waist-hip ratio (WHR) is a mean to estimate the degree of upper and lower abdominal fat, which is increased in android obesity. Since polycystic ovary syndrome (PCOS) is a state of chronic anovulation, it is reasonable to study the presence of insulin resistance (IR), body mass index (BMI) and WHR in patients with anovulatory dysfunctional uterine bleeding (DUB).

AIMS and OBJECTIVES

The aims and objectives of the study were to investigate markers of IR in women with chronic anovulation without features of PCOS. The markers studied were:

• Fasting plasma insulin (FPI) levels.
• Ratio of fasting plasma glucose to fasting plasma insulin (FPG:FPI).

MATERIAL and METHODS

This study was conducted in the Dept. of Obstetrics and Gynecology, SVBP Hospital, LLRM Medical College, Meerut for period of 1 year. (November 2003 to 2004), 37 outdoor attending patients who diagnosed as a case of anovulatory bleeding on the basis of history and clinical examination formed the subject of this study.

Inclusion Criteria

• Postmenarchal adolescent 2 years after menarchae.
• Perimenopausal women with anovulation as determined by clinical presentation of menstrual dysfunction ranging from irregular cycle to amenorrhea.

Every eugonadotrophic, nonhyperprolactenemic amenorrhea were included.

Women were examined for the following parameters

• BMI = (if >27 = obesity)
• Waist circumference (WC) (if >90 cm = obesity)
• WHR (if >0.85 = android obesity)
• FPG and FPI ratio (if <4.5 = IR)
• WC was the smallest circumference between rib cage and iliac crest.
• Hip circumference was the maximal circumference over the buttocks.
• The statistical tests applied on the data determining the frequency distribution of obesity, WHR, FPG/FPI, hyperinsulinemia in general population is binomial test.

The statistical test applied to determine the significant association between markers of IR and clinical features of anovulatory DUB were Chi-square test/fisher exact test.

The p-value <0.05 was taken as statistically significant.

OBSERVATIONS and RESULTS

In the present study the mean age of patient was 24.7 years. But maximum number of patients belonged to 26-30 years of age. Out of total 37 cases, 64.9% had BMI >27, which is statistically significant. Among total cases, 75.7% had WHR >0.85, 62.2% had hyperinsulinemia and 29.1% had IR which was statistically significant (Table 1).

Out of 11 IR patients 90.9% were obese and 9.1% were nonobese but this association was found insignificant (p = 0.33) (Table 2).

All patients of IR had WHR >0.85 and this association was found statistically significant (p = 0.025) (Table 3).

Among 11 IR patients, 90.9% had hyperinsulinemia and 9.1% had normal insulin level, which was statistically significant (p = 0.020) (Table 4).

Out of 23 patients with fasting hyperinsulinemia 65.2% were obese and 34.8% were nonobese. Association between these entities was statistically insignificant (p = 0.613) (Table 5). Among all patients with fasting hyperinsulinemia 87% had android obesity (WHR >0.85) and 13%  had WHR <0.85. This association between hyperinsulinemia and android obesity was statistically significant.

DISCUSSION

In the present prospective study 37 patients with chronic anovulation without any clinical features of hyperandrogenism were evaluated. In terms of distribution of body fat, WHR >0.85 (i.e. android obesity), was found in 28 patients (75.5%). This observation was consistent with various studies which showed that android obesity was related with metabolic disturbances.^1-5 Intra-abdominal fat accumulation causes metabolic derangement which results in altered physiology. The presence of IR was observed in
11 (29.7%) subjects from study group of 37 subject. Evidence of IR in PCOD subjects is available in literature. But this significant association with chronic anovulation shows that IR is a feature not specific to PCOS but associated with anovulation. Among 11 IR subjects 90.9% were obese and only 9.1% were nonobese. This observation was consistent with the previous observation on patient with chronic anovulation who concluded from their study that association between percentage body fat and FPG/FPI was not significant.⁶

WHR >0.85 i.e. android obesity was found in 75.5% of chronic anovulatory patients.

All cases with increased WHR (>0.85) (75.5% of total), were found with IR. This is consistant with the previous studies which show that it is the intra-abdominal fat accumulation which is associated with metabolic abnormalities.^1,7-9

From 23 patients with fasting hyperinsulinemia, 65.2% were obese and 34.8% were nonobese. Previous study by McAuley KA, et al, showed plasma insulin concentration as a useful surrogate marker of IR.¹⁰

Out of 23 patients with fasting hyperinsulinemia 87% had android obesity, thereby showing that derangement of insulin levels are associated with accumulation of intra-abdominal fat. This finding is consistant with the observation in which WHR was found to be a significant predictor of insulin concentration.^3-5

CONCLUSION

Thus in chronic anovulatory patients there is presence of derangement in carbohydrate metabolism, which may lead to development of type 2 diabetes mellitus in these patients. Although, percentage of patients with IR were less, it had the best association with other markers of IR.

While presence of IR and markers of IR are hallmark of PCOS, the present study though involving small number of patients does indicate a similar biochemical derangement in non PCOS chronic anovulators.

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