PCOS is one of the most common endocrine disorders which continue into and after menopause. In recent years, it has become apparent that PCOS is not only the most frequent cause of anovulation
and hirsuitism, but is also associated with characteristic metabolic disturbances that have important implications for long term health [23
]. There are little studies of PCOS in perimenopausal women.
Of 100 women of 35-54 years who had presented with menstrual abnormalities with or without hirsutism and obesity, 12% had PCOS as per inclusion criteria (two of them had hypothyroidism also). Incidence is lower than reported, 37.3% in Kashmiri women presenting with hirsutism by Zargar et al [40
] but they had included women of 15-75 years. PCOS has been well studied in young women. It is reported that PCOS is diagnosed in at least 5% to 10% of women between adolescence and menopause, making it one of the most prevalent hormonal disorders in this population [41
]. Koivuner et al. [42
] reported that PCOS varies with age but continues to be more common among women aged less than 35 years than in those above 35 years. Incidence of PCOS in perimenopausal women is not well known. Present pilot study is of women beyond 35 years of age without any record or history suggestive of PCOS so as to say it could have been continuation of PCOS at young age. Studies are needed about de novo PCOS in perimenopausal women as well as follow up of young women with PCOS through menopause which as of now does not seem to be easy in India unless women keep records and population based studies are done. Present study is of perimenopausal women where studies are scarce.
In the present pilot study with few cases it was found that more women with PCOS were from upper class but difference was insignificant (p value >0.05,). This needs further studies in a large population. Of 100 women, 6% women presented with oligomenorrhoea, 4% hypomenorrhoea, 8% oligohypomenorrhoea, 6% secondary amenorrheoa, 24% had menorrhagia, 32% had infrequent heavy uterine bleeding and 20% had polymenorrhagia. More women with oligomenorrhoea had PCOS (33%), 4 out of 12, similar to the study done by David et al. [4
] who reported that 70% of women of PCOS have oligomenorrhoea however their study subjects were of 15-45 years. In the present pilot study most of the women with PCOS were obese, having hirsutism with menstrual abnormalities (p value <0.05, significant difference). Association of obesity was significantly high, 9 (75%) of 12 had WHR >0.8 with PCOS compared to those with no PCOS, WHR >0.8 in 40%, (16 out of 40). (p<0.05). Of 12 women with PCOS, 7 were obese similar to the study reported by Robert et al. [34
], 35-50%. Hyperandrogenism is the prominent biochemical abnormality in women with PCOS. 6 (50%) of 12 had clinical features of hyperandrogenism. However Winter et al. [43
] reported that hyperandrogenism partly resolves before menopause in women who have PCOS in young age. The reduction in hyperandrogenism explains the tendency of some women with PCOS to menstruate regularly as they grow older [44
]. Etling et al. [45
] also suggested that menstrual cycle abnormalities tend to normalize with age. This could be due to diminishing follicle cohort following ovarian aging [46
]. It is possible that younger women with PCOS become better over the years, so follow up of women towards menopause and beyond is needed. Welt et al. [47
] reported that inhibin known to stimulate ovarian androgen production decreases in normal women during middle age and contributes to decrease in testosterone production. It may also result from an age-related decrease in one of the testosterone biosynthesis enzymes, P450c17, implicated, in the development of PCOS [48
]. However it could be that in those in whom such change does not occur will have menstrual abnormalities. Testosterone remains elevated in older women with PCOS, and may contribute to their increased risk for cardiovascular disease, endometrial cancer, and other diseases.
Of 12 women with PCOS after clinicosonographic biochemical findings, 8 had fibroid uterus, all underwent hysterectomy. Polsen et al. [49
], Teleman and Mahailovici [50
] also reported that hysterectomy, because of fibroids and menorrhagia had to be done more frequently among PCOS subjects.
In the present study PCO was significantly more in women with PCOS (75%, 9 out 0f 12) compared to women with no PCOS (20.45%, 18 of 88). Welt et al [51
] compared USG appearance of ovaries in normal women with PCOS and reported that 14% of women with PCOS did not have PCO on USG. Hence absence of PCO does not rule out PCOS and presence does not diagnose PCOS.
Of 12 women who had PCOS, 8 (66.66%) had insulin
resistance. Shayya et al. [52
] reported that the impairment of insulin metabolism is central to the pathophysiologic cascade of PCOS. A positive but weak correlation between age and fasting glucose
to insulin ratio has been reported, suggesting that a slight amelioration of insulin resistance occurs in PCOS with age [39
]. Earlier Poretsky [55
] reported that coexistence of insulin resistance and ovarian hyperandrogenism is a well-known phenomenon although the precise mechanism has not been clearly defined, the hypothesis that hyperandrogenism of insulin-resistant state is due to ovarian stimulation by high levels of circulating insulin. Rosenbaum et al. [56
] reported a defect in glucose transport as a result of diminished production of GLUT-4 glucose transporter protein, a cause of insulin resistance in women with PCOS. In the present study all, perimenopausal women with PCOS had metabolic disorders (4 had Diabetes mellitus, 3 had hypertension, 2 had diabetes and hypertension, 2 had hyperlipidemia with diabetes and hypertension, one had hypothyroidism, significantly higher compared to women with no PCOS or hypothyroidism or hyperthyroidism. Researchers reported that PCOS is associated with characteristic metabolic disturbances that have important implications for long term health [23
]. Most affected women are hyperinsulinemic and have altered lipid profiles, hypertension, increased risk of cardiovascular diseases. In perimenopausal women with PCOS, dyslipidemia is variable, significantly higher triglycerides, low density lipids, cholesterol
and high density lipids [57
] and is related to elevations in circulating androgen levels [31
]. The incidence of heart disease with menopause is 6-7 times greater in women with PCOS, than in normal population [22
]. Dursun et al. [24
] did a study on patients with PCOS and reported increased risk for the development of hypertension and atherosclerotic heart disease (AHD). Kidson [10
] have reported that 42% of women before the age of 60 years undergoing coronary angiography for ischaemic heart disease had PCO on ultrasound and out of these 10% were diagnosed to have PCOS. Kandarakis et al [29
], and Wild et al [60
] report that clinical presentation of PCOS is highly variable, so is missed unless investigated. These women are prone to developing complications obesity, impaired glucose tolerance and type-2 diabetes, dyslipidemia, metabolic syndrome and cardiovascular disease and endometrial cancer. Those with metabolic syndrome and/or type 2 diabetes mellitus are at high risk for cardiovascular disease (CVD). BMI, waist circumference, serum lipid/glucose, and blood pressure determinations are recommended for all women with PCOS, oral glucose tolerance testing in those with obesity, advanced age, personal history of gestational diabetes, or family history of type 2 diabetes mellitus.
The PCOS is a familial disorder, though genetic basis of the syndrome remains to be studied in depth. Familial clustering of PCOS and its symptoms reflect a strong genetic pathogenesis contributing to the development of PCOS [61
]. In the present pilot study overall 10 (83.33%) of the 12 women with PCOS had significant positive family history of diabetes, hypertension, ischemic heart disease and menstrual irregularities in mother, 36 (40.90%) of 88 women without PCOS had significant family history (p<0.05). Exact mechanism of inheritance has not been uncovered by researchers despite rigorous efforts. Ovalle et al. [62
] after review of literature, have reported that it remains to be determined whether PCOS and type 2 diabetes mellitus represent no more than different clinical manifestations of the same insulin resistance syndrome, with their phenotypic differences due to the presence or absence of a coincidental genetic defect at the level of the ovary or pancreas, respectively, or representing the result of etiologically different subtypes of IR syndromes. Sheehan [14
] reported that the significance of epigenetic role play in PCOS is evident from the fact that active amendments in lifestyle or dietary ingredients attenuate some of the detrimental effects and so adherence to regular physical activity for weight loss with intake of food bearing low glycaemc index and fat content have perpetually been the first line of management of PCOS. Also, existing evidence on epigenetic modifications in development of PCOS associated co-morbidities like CVD and type–2 diabetes mellitus (T2DM) are a definite prelude towards imminent epigenetic studies in PCOS [15