A Clinical Study on the Gynaecological Parameters Pertaining to Polycystic Ovarian Syndrome (PCOS)

Introduction

Polycystic ovarian syndrome (PCOS), a multifactorial endocrine disorder that occurs due to both environmental and genetic causes, has foremost influence on women of reproductive age.¹ Globally, PCOS affects 4% to 20% of women of reproductive age group.² Prevalence of PCOS in India ranges from 3.7% to 22.5%.³ This varied discrepancy in prevalence is because of the ethnicity of the population studied, criteria used for diagnosis, socioeconomic status, and access to medical care.² PCOS was first named as ‘Stein-Leventhal syndrome’ in 1935 based on several findings in obese infertile women.⁴ Although the clinical features of PCOS are diverse, the classical characteristic features of this syndrome include hyperandrogenism which can be clinical or biochemical, irregular anovulatory cycles, glucose intolerance and insulin resistance (IR). Women with PCOS have a higher prevalence of obesity which tends to be of the android/ central type where there is visceral fat accumulation.^5,6 It is the primary cause for IR and future implications include diabetes and cardiovascular diseases. Central obesity further intensifies IR, irrespective of the weight of the women, as android obesity is also observed in lean PCOS women with normal body mass index (BMI).⁷ IR is a significant feature of PCOS seen in approximately 50–70% of the affected women.⁸ The main concern in women of reproductive age group with PCOS is infertility because of oligomenorrhea or secondary amenorrhea leading to anovulation. Post-treatment for conception, using ovulation induction or assisted reproductive technology, usually has a poor pregnancy outcome in women with PCOS. There may be an increased risk for spontaneous abortions, gestational diabetes, preeclampsia, and preterm births.⁹

The aetiopathogenesis of infertility and spontaneous abortions include obesity, IR, hyperandrogenism, and elevated levels of luteinizing hormone (LH). They are also the main features of PCOS. Due to concerns about the associated morbidities of PCOS, this study aimed to see if there was any significant correlation between certain early clinical findings and PCOS. Early diagnosis and non-invasive intervention will go a long way in helping women with PCOS lead a healthier life without the associated comorbidities.

Materials and Methods

This was an observational cross-sectional study conducted among women attending the Obstetrics and Gynaecology outpatient department (OPD) in a medical research centre. The study was carried out between September 2018 and March 2020 after the ethical clearance (VIEC/2018/APP/048) was obtained from the Institutional Ethics Committee. The study was conducted following the ethical principles mentioned in the Declaration of Helsinki. Consenting women aged between 18 to 45 years were included in the study. Women were diagnosed with PCOS based on the Rotterdam’s 2003 criteria¹⁰ which states that the presence of at least two of the following is required: irregular menstrual cycles (anovulation/ oligoovulation), clinical hyperandrogenism (hirsutism, acne, or alopecia)/ biochemical hyperandrogenism (high androgen levels) and polycystic ovaries on pelvic ultrasound scanning. Women clinically diagnosed with Congenital adrenal hyperplasia, Cushing’s syndrome, Androgen secreting tumours and Functional hypothalamic amenorrhea were excluded from the study.

Informed written consent was obtained from all the subjects. Menstrual history like age of menarche, type of menstrual cycle (Regular, oligomenorrhea or secondary menorrhea) was noted. Anthropometric details such as BMI which was calculated as weight (kg)/ height (m)² , waist circumference (WC) measured midway between the lowest rib and just above the belly button, hip circumference (HC) measured at the widest part of the buttocks or hip and waist – hip ratio (WHR) were calculated. Details regarding type of infertility (primary or secondary) and duration of infertility were noted. Pregnancy loss history, if any, was noted and also if the patients had spontaneous abortions or recurrent pregnancy loss (RPL) characterised as loss of three or more consecutive pregnancies was noted. Acanthosis nigricans defined as dark velvety hyperpigmentation of the skin usually in the posterior and lateral creases of the neck, the axilla, and the groin was noted and considered as a surrogate marker for IR.

The data was analysed using descriptive statistics. Quantitative data was presented as n, mean, standard deviation, range, whereas qualitative data was presented with frequency and percentages. Comparison between two groups and inferential data was evaluated using p-value and 95% CI with Chi-square test. Excel and Statistical Analysis System (SAS) version 9.4 software have been used for the analysis.

Results

A total of 90 patients who fulfilled the Rotterdam criteria were included in the study. The age group of the subjects ranged between 20 years to 42 years with a mean of 27.91 ± 4.49 years.

Age of menarche ranged from 11 years to 17 years among these women. The mean age of menarche was 12.97 ± 1.175 years. Menstrual characteristics of oligomenorrhea and secondary amenorrhea were seen in 51 and 14 women, respectively. Regular menstrual cycles were seen in only 25 of the 90 women as shown in Figure 1.

BMI was calculated as weight (kg)/ height (m)² and based on WHO criteria, was classified as underweight when BMI <18.5, BMI of 18.5 to 25 as normal, 25 to 30 as overweight, 30 to 35 as obese and BMI > 35 as being severely obese. BMI characteristics of study population is depicted in Table 1.

The WHR was calculated as waist (inches)/ hip (inches). WC > 88 cms and WHR ≥ 0.85 is indicative of abdominal obesity^11,12 and this was seen in 67 (74.4%) and 86 (96.6%) of the women, respectively. The other anthropometric details are presented in Table 2.

Infertility was observed in 53 (58.8%) out of 90 subjects. Amongst these, 44 women had primary infertility and nine had secondary infertility. The duration of infertility ranged between 1 year and 12 years and the mean was 3.42 ± 2.472 years. Infertility when compared with BMI and WC in the present study was not statistically significant as seen in Table 3.

Spontaneous abortions were observed in 24 (26.6%) out of 90 women. Among the 24 women, 18 patients had spontaneous abortion once, five patients had spontaneous abortion twice, and one patient had RPL. Based on Chi square test of independence, there was no significant association between body mass index (BMI), waist circumference (WC) & SA which is depicted in Table 4.

Acanthosis nigricans (AN), a surrogate marker of insulin resistance was observed in 61 (67.7%) patients. A Chi square test of independence was performed to examine the relation between BMI, WC & AN (Table 5). It shows the relation between these variables to be significant. Subjects with BMI ≥ 25 kg/m² which includes categories of overweight, obese and severely obese, and subjects with WC ≥ 88 are more likely to get AN than those with a BMI < 25 kg/m² (normal and underweight) and WC < 88.  

Discussion

This cross sectional, observational study was carried out in women attending the gynaecology OPD in a medical research centre. After screening, 90 women were found to be eligible and were enrolled in the study after they provided consent. They attended the OPD with chief complaints ranging from menstrual irregularities to inability to conceive. Some were previously diagnosed with PCOS and at the same time, almost all were aware of the condition called PCOS.

The age of the 90 subjects varied from 20 years to 42 years with the mean age being 27.91 ± 4.49 years. Onset of menarche ranged between 10 years to 17 years where the mean age was found to be 12.97 ± 1.17 years. Similar findings were reported in the study by Spandana JC et al. where the mean age of menarche was 12.62 ± 1.11 years.¹¹ Carroll J et al.¹³ concluded in their study that age at menarche in women with PCOS is influenced by BMI and genetic variants; meaning that those with a high BMI tend to have an early menarche and those with a lesser BMI have a late age at menarche. It is the genetic association of variant rs7759938 gene which plays a major role than BMI in determining the menarche. Women with PCOS and a normal BMI of <25 kg/m² carry the C allele at rs7759938 whereas those with a BMI >25 kg/m² , considered overweight, carry the T allele at rs7759938 gene.

The menstrual history in the present study showed 27.7% women to have regular menstrual cycles, same as in another study where 37% of women with PCOS had regular cycles.¹¹ Menstrual dysfunction which is commonly observed in women with PCOS is treated symptomatically without any intervention. In a study by Panidis D et al.¹⁴ 1285 women with PCOS had menstrual dysfunctions like oligomenorrhea and secondary amenorrhea. In addition, further comparison of insulin profiles showed increased IR compared to subjects with regular cycles. IR is one of the major key factors in increasing the production of LH due to rapid gonadotropin releasing hormone pulse frequency. This rise in LH causes thecal hyperplasia which in turn leads to hyperandrogenism. Increased secretion of androgens supresses the production of follicle stimulating hormone and hinders growth of the dominant follicle in the ovary.¹⁵ This results in anovulation which ultimately leads to irregular menstrual cycles in women with PCOS. In this study, 56.6% women had oligomenorrhea and 15.5% showed secondary amenorrhea. Other studies have also reported oligomenorrhea and secondary amenorrhea to be 74%, 69.2%, 20% and 26%, 21.1%, 43%, respectiv ely.^16,17,18Anthropometric details of BMI, WC, HC and WHR were recorded in women with PCOS as adiposity in the abdominal region plays a crucial role in infertility and abortions. In the present study, 35 women had a BMI < 25 kg/m2 and 20 among them were diagnosed with infertility. In addition to having normal BMI and infertility, 18 of the 20 women had a high WC and WHR i.e., central obesity.

Primary infertility is when a woman has never been pregnant and secondary infertility is when the woman had at least one prior pregnancy.¹⁹ Primary infertility was observed in 44 subjects and secondary infertility was seen in nine women. Spandana JC et al also reported primary infertility (82%) and secondary infertility (18%) in a cross-sectional observational study that included 100 women with PCOS.¹¹ The duration of infertility ranged between 1 to 15 years in their study, with a mean age of 7.02 ± 3.29 years. In the present study, the mean duration of infertility was 3.42 ± 2.47 years and ranged between 1 to 12 years.

Studies have concluded that obesity exacerbates the reproductive and metabolic features of PCOS.¹⁹ A community-based cohort study among Australian women found a 15-fold increase in risk of infertility in women diagnosed with PCOS, independent of BMI.²⁰ Subfertility is seen in obese ovulatory women as reported in another cohort study by Van Der Steeg JW et al.²¹ Women with ovulatory cycles and with at least one patent tube were included in this study while women with anovulatory cycles and two-sided tubal pathology were excluded. It was concluded that the probability of pregnancy reduced by 4% when the BMI is more than 29 kg/m² . This was the first prospective cohort study to claim an association between infertility in women with ovulatory cycles and BMI. With obesity being the common factor here, infertility is further worsened with a higher BMI.

Overweight (BMI ≥ 25 kg/m² ) and obese women (BMI ≥ 30 kg/m² ) have an increased risk of miscarriage.²² In the case control study by Landres IV et al,²³ it was found that euploid abortions were seen in 47.9% (n=204) of women with PCOS. In our study, eight women with BMI < 25 kg/m² and 16 women with BMI ≥ 25 kg/m² had spontaneous abortions, respectively.

It is a proven fact that obesity increases the rates of spontaneous abortions.²⁴ Regardless of the diagnosis of PCOS, reproductive concerns are frequent in obese women, with the link between PCOS and obesity being intricate and not well understood.5 The prevalence of polycystic morphology of the ovaries amongst women with recurrent miscarriage was 40.7% in a study by Rai R et al.²⁵ It also states that ovarian morphology by itself is not a risk factor for pregnancy loss.

WHR ≥ 0.85 is considered an indicator for the presence of PCOS and this predicts the occurrence of metabolic syndrome in the future in these women.²⁶ They recorded a WHR ≥ 0.85 in 45.8% subjects in their study. It was concluded that instead of BMI, the waist circumference or the WHR can be used for predicting obesity related health issues.¹² However, in a review by Lord J et al⁶ to determine whether measuring waist circumference is the best method for assessing central obesity, they opine that WC is a much better predictor of metabolic consequence when compared to WHR. In another study by Kurpad SS et al, they found that as the prevalence of abdominal obesity using waist circumference was higher than WHR, WC correlated better with BMI than WHR.²⁷ In the present study, WHR ≥ 0.85 was present in 86 subjects (96.6%) with a mean of 0.93 ± 0.051, while WC was seen in 67 subjects (74.4%) with a mean of 94.01 ± 4.42 cm. In a study by Alves AC et al,²⁸ 145 cases of PCOS from a population-based birth cohort study were selected to determine the impact of abdominal obesity by investigating their metabolic profile where WC was used as the measure of central obesity. The authors concluded that abdominal obesity and increased WC aggravates the risk of metabolic and cardiac dysfunction in women with PCOS.

In this study, neither the BMI nor the abdominal obesity increased the risk of spontaneous abortion and infertility as seen in Tables 4, 5. This correlation could not be justified probably due to the smaller sample size of this study.

Kahn and colleagues²⁹ first identified the link between acanthosis nigricans and insulin resistance in 1976. Patidar PP et al³⁰ also concluded in their study that AN can be used as a clinical surrogate for assessment of severity of IR. In a recent cross-sectional study conducted among 146 women with PCOS in Jordanian population, AN was seen in 46 women (31.5%).³¹ In another study by Ramanand SJ et al³² in 120 newly diagnosed postpubertal PCOS patients, AN was observed in 53 women (44.16%) where obesity positively correlated with the same. Similar observation has been made in the present study in which out of 90 subjects, acanthosis nigricans was noted in 61 (67.7%) subjects. Amongst these 61 women with AN, 80% of them had a BMI ≥ 25 kg/m2 and 74.6% had WC ≥ 88 cm. Women with BMI < 25 kg/ m² and WC < 88 cm are less likely to develop AN.

In another observational cross-sectional hospital-based study by Upadhya JP³³ which included 200 women with PCOS, AN was observed in 33 (16.5%) women. Amongst them, 31 had WHR more than 0.81 indicating that body fat distribution might be associated with AN. Gill H et al³⁴ indicated in their study that Asian Indians are more susceptible to IR even with a low BMI because of the presence of higher percentage of body fat and abnormal adiposity. IR is also known to have an impact on the maturation of the oocyte and implantation of the zygote instigating an early pregnancy loss.⁹

Conclusion

In women with PCOS, android obesity and IR form a malicious cycle fuelling each other continuously. In the present study, a wide array of symptoms were presented by women with PCOS which correlated with the measurements of BMI, WHR and WC. The significance of results in this study has been affected by the duration and the sample size and an extended study may prove to have significant values regarding infertility, spontaneous abortions and metabolic correlation in PCOS, with emphasis on AN.

Conflict of interest

None

Acknowledgement

I would like to acknowledge Dr. Prabhakar G, Dean, VIMS & RC for the opportunity. My sincere gratitude to Dr. Rajini T and Dr. Shobha T R, Senior consultant, Department of OBG, Sanjay Gandhi Hospital for their guidance. Many thanks to Dr. Varsha Mokashi, Head of Department of Anatomy, and the faculty and staff of the Departments of Anatomy and Gynaecology, VIMS & RC, for their support and encouragement.