CLINICAL AND GENETIC STUDIES OF POLYCYSTIC OVARIAN SYNDROME

Abstract

Polycystic Ovarian syndrome (PCOS) is the most common endocrine disorder of reproductive age group and its familial presence has been proved. The present study was carried out in two parts. First part comprises clinical, sonographic, endocrine, biochemical characteristics and second part includes epidemiological aspect and association of known loci with micro satellite markers of PCOS. At the end, relationship among clinical, endocrine and association of micro satellite markers ~ith PCOS loci was done. This study was carried out in 6 Pakistani families for which data were obtained through interview of the subjects from Gynecology advisory Centre, Islamabad. PCGS and non-PCGS women were diagnosed applying diagnostic criteria for PCGS of Rotterdam 2003 consensus. This study was carried out from Nov 2001 to December 2005 . Main clinical features recorded for PCGS and non-PCGS women were menstrual problems, obesity, sub-fertility and hirsutism. It was found that 38.24 % of PCGS women were obese (BMI 30-35 Kg/m2 ) in these families . Menstrual cycle problems (secondary amenorrhea and oligomenorrhea) of PCGS women were seen in 32.40 % and 52.90 % respectively. Sub-fertility was found in 50 % of PCGS women. Moderate and severe hirsutism in PCGS women was present in 47 % ane:: 5.8 % respectively. Acanthosis nigrans was present in 52.9 % of PCGS women. Sonographic findings like follicular number with small diameter (2-8 mm), stromal thickness in mm, ovarian volume were significantly more in PCGS women than in non-PCGS women. Mean serum LH levels in pre-menopausal PCGS women were significantly more compared to non-PCGS pre-menopausal women. Raised serum LH: FSH ratio in pcas women was seen in 32.4 % which was significantly high compared to non-PCGS women. Serum fasting insulin levels were more than 10 uIU/l in both peGS and non-PCGS women which was a manifestation ofhyperinsulinemia. Triglyceride levels and fasting blood sugar levels in non-PCGS were more compare to peGS women. Diabetes mellitus type 2 was present in 17.8 % of PCGS andt:1onpeGS women. In the second part of the study, recessive mode of inheritance was ascertained in all of the six families . Association of steroid marker D15S519 was seen in family 5. Likewise, marker D5S822 was strongly linked to family 2. Weak association with insulin markers were found in family 1 and 6. Relationship of clinical features and Vl endocrine parameters with known loci was also an interesting feature of the study. In family 5, mean serum testosterone levels were maximum and association with steroid marker D15S519 was seen here. In family 2, mean serum LH levels were highest and association with marker for follistatin gene D5S822 was found. In conclusion, we predict from this study that as there are more clinical manifestat~ons in peas women of these families but due to its genetic etiology, endocrine and metabolic problems are more or less equalent in these families. So, early prevention by life style modification is the most understood method to save from long term complications.