Prevalence of hyperandrogenism in Iraqi women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a mainly common endocrine disorder. Hyperandrogenism is the major standard in the diagnosisof PCOS development.Eighty women diagnosed with PCOS and twenty healthy women(aged 20-40 years)were enrolled in this study which was conducted at the infertility clinic of Kamal AL-Samaraay Hospital/ Baghdad. The diagnosis of PCOS was made according to the Rotterdam criteria. Body mass index (BMI, Kg/m 2 )was calculated by a specific formula. History of menstrual irregularity, hirsutism, acne, and alopecia was taken. Hormone levels in serum, namely luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone were measured in all patients and control subjects.There was a statistically significant difference (P <0.05) in the BMI between the PCOS and control women.Also, the prevalence of overweight and obesity was much higher in PCOS women than in their matching control. The serum levels of LH, FSH, and testosterone were significantly different (P <0.05) in PCOS as compared to healthy women. Clinical hyperandrogenism (hirsutism and alopecia) were present in most of PCOS women, while acne wasa less useful clinical sign of hyperandrogenism.Inaddition, the prevalence of hirsutism and alopecia was increased in obese when compared with overweight and lean PCOS women.

-Ultrasound of the ovaries (presence of 8 or more sucapsular cysts ≤10 mm in diameter with augmented ovarian stroma). -The laboratory results which included endocrine secretion evaluation by measurement of hormonelevels in serum, namely, luteinizing hormone (LH), follicle stimulating hormone (FSH), and Testosterone (T).Serum concentrations of three hormones were measured by using mini-VIDAS (VIDAS 12 model, 1992), through an enzyme linked fluorescent assay (ELFA) technique. The exclusion criteria included the use of hormonal contraception, fertility medications in the three months prior to enrollment, hyperprolactinemia, thyroid dysfunction, cushing's syndrome, and congenital hyperplasia. Statistical analysis of data was carried out using (SPSS Version 20). Significance of variances was assessed using t-test and a P value ≤ 0.05 was considered to be significant.

3-Results Body mass index (BMI)
An increase in BMI was found in PCOS patients as compared with the control group. There was a significant (P<0.05) difference in the mean of BMI between the PCOS group (32.3±0.5 g/m 2 ) and the control group (28.8±1.0 kg/m 2 ) as shown in table 2. -The difference between the two groups was statistically significant (*= P <0.05).
In the present study, we classified the body weight in the studied groups according to BMI, as shown in table 3. The prevalence of overweight and obesity in women with PCOS is much higher than in their matching control.

(*P<0.05)= Significant Menstrual cycle dysfunction
In the present study, the whole PCOS group was split into three subgroups according to the menstrual status; fourteen patients were with eumenorrhea (17.5%), eight patients were withabnormal uterine bleeding (10.0%), forty seven patients were with oligomenorrhea(58.75%) and eleven patients were with amenorrhea (13.75%), as shown in table 5. The differences were significant (P<0.05) among lean, overweight, and obese PCOS patients.  Table-6. The difference between the twogroups was statistically significant (P <0.05).

Serum FSH level
The mean serum level of FSH for the control group was 7.1±0.4 mlU/ml, whereas, in the group of PCOS patients, it was 4.2±0.5mlU/ml, as shown in table 6.The difference between the two groups was statistically significant (P <0.05).

Serum testosterone level
The mean serum level of testosterone within the control group was 0.3±0.03 ng/ml, while, in the group of PCOS patients, it was 1.05±0.1ng/ml, as shown in table 6.The difference between the two groups was statistically significant (P <0.05).

LH/FSH ratio
The LH/FSH ratio for patients with PCOS was 1.8±0.6 and for the control group was 0.5±0.3, with a significant difference between the two groups, as shown in table 6. -The difference between the two groups was statistically significant (*= P <0.05).

4-Discussion
Results of this study showed that women with PCOS had higher BMI than age-matched controls.Also, the prevalence of overweight and obesity was much higher in PCOS women than in their matching controls. Obesity condense the metabolic disorder and clinical criteria in women with PCOS. This finding was in agreement with a study by [15]whichindicated that obesity is a familiar morbidity associated with PCOS and that the accompanying insulin resistance is a key pathogenesis of PCOS. The relationship of obesity with PCOS was already illustrated, which gives insight into the expansion of typical criteria for obesity in PCOS. Similar results by other reports [16,17] were concluded in women with PCOS, where mean BMI in PCOS women was significantly higher than the control groups. Valkenburg et al [18] revealed that obesity (BMI ≥ 30 kg/m 2 ) occurred more recurrently in PCOS women compared with the control group, while another study [19]indicated that the threat of PCOS is minimally enhanced with obesity, though the degree of obesity of PCOS patients has augmented, similar to that observed in women without PCOS in the present study. This information indicates that obesity in PCOS women reflects environmental factors to a great degree. Apridonidzeet al [20] stated that the increased weight and obesity (mostly abdominal) were widespread in women with PCOS, while another investigation found no difference in BMI between any of the PCOS groups and their matching controls [21].
Clinically, hyperandrogenic women with PCOS demonstratedhirsutism, acne, and temporal balding. The current study revealed that the frequency and percentage of clinical hyperandrogenism were augmented with increased BMI and that there were significant differences (P<0.05) in hirsutism, acne, and alopecia among lean, overweight, and obese PCOS patients. The clinical hyperandrogenism is augmented by overweight and obesity.We found that obese women with PCOS had a higher prevalence of clinical hyperandrogenism and, hence,obesity was considered to be responsible for hyperandrogenemia and the resulting hormonal abnormality and reproductive disorder in women with PCOS. These results agree with other authors [22] who found that PCOS women with obesityare susceptible to have higher hirsutism and acne signs than their lean counterparts. In fact, sex hormone binding globulin levels are decreased in obese women with PCOS, particularly if they present with abdominal obesity. It was found that overweight girls had significant hyperandrogenemia compared to their counterparts with normal weight [23], findings indicating that obesity plays an exciting role in the early progress of androgen excess, which may render PCOS more rapid. Corbould [24]reported that a key feature of PCOS is the increased levels of androgens. A side from their effects on ovarian function and phenotypical features, like alopecia, they also affect where fat is stored in the body.Majumdar and Singh [25]found that hyperandrogenism was present with hirsutism and acne was significantly higher in the overweight PCOS women.
A study conducted in Iran reported that women who had hirsutism were significantly more obese and younger than those without hirsutism [26]. Another study from Germany assessed the class of life reported by 120 PCOS women and the outcome revealed obesity and hirsutism to be associated to lower class of life scores [27].
It was alsoreported that the prevalence of menstrual irregularity and the clinical features of hyperandrogenism (hirsutism, acne, alopecia) were elevated in obese than in lean women with PCOS, but there was no statistically significant difference between the two studied groups [28].However, another study demonstrated that42% of the PCOS women had typical BMI (lean), but the clinical signs (hirsutism and acne) were analogous to PCOS women with increased BMI (overweight/obese) [29].Norman et al [30] reported that PCOS is a varied endocrine disorder. The main endocrine disturbance is an extreme androgen secretion or activity, with frequent clinical signs of hyperandrogenism such as hirsutism, acne, and alopecia can appear as a result of hypersecretion of androgen by the ovary. Azziz et al [13]showed that about 60% of PCOS women are hirsute, which is the most common clinical feature of hyperandrogenemia. Ikhenaet al [31] mentioned thatscalp hair thinning is a prevalent sign in PCOS women. Tissue, rather than systemic endocrine environment appear to be of significance for scalp hair growth and density. Birchet al [32] found that PCOS women were six times more possible to distinguish scalp hair thinning compared with 6% incidence described in their matching controls. In the present study, we showed that 65.0 % of PCOS patients had clinical signs of alopecia, while a previous study [33] reported that alopecia is common in 22% of women aggregating diagnostic criteria for PCOS. Androgenic alopecia is linked with other aspect of clinical hyperandrogenism, but not with more risk of biochemical hyperandrogenemia or metabolic disorder than with PCOS alone.
Menstrual disturbance was the main frequently present complaint in PCOS women. The present study showed that 82.5 % of PCOS patients had clinical signs of menstrual disturbance (abnormal uterine bleeding, oligomenorrhea and amenorrhea) compared to 94% in a previous study [28]. Results of this study showed that obese PCOS women had a higher occurrence of menstrual dysfunction (abnormal uterine bleeding, oligomenorrhea, and amenorrhea) than lean and overweight PCOS women. This explains the fact that increased BMI was also associated with an increased rate of menstrual dysfunction.High serum levels of LH and testosterone in PCOS women may be associated with menstrual cycle dysfunction.
However, it was demonstrated that 79.2% of PCOS women with BMI > 23 and 44% of those with BMI ≤ 23 were with menstrual disturbance [25]. Other studies [22,34,35] showed that, as compared to non-obese PCOS women, obese women with PCOS have more menstrual irregularity and uterine dysfunctional bleeding, in additionto an increased occurrence of infertility, which were also related with an abdominal distribution of fat. Harris et al [36] reported that extended and irregular menstrual cycles, a feature of PCOS, was related with elevated androgen and slight sex hormone binding globulin levels, and that this altered hormonal environment may raise the risk of certain histologic ovarian cancer. Azzizet al [37]found that 75-85 % of women with PCOS had clinically obvious menstrual disturbance, while another studyfound that 75% of PCOS patients were with clinically obvious menstrual disturbance [38]. It was reported thatirregular menstrual cycle was analogous in the lean and overweight/obese PCOS groups [29].
The results of LH, FSH, and testosterone levels as well as LH/FSH ratio in the present study were in agreement with the results of previous investigations [39][40][41][42] who showed that theelevations in testosterone and LH levels, accompanied by reducedFSH level and higher LH:FSH ratio, were the main endocrine changes observed in women with PCOS. Lewandowski et al [43] found that PCOS women have an increased speed of hypothalamic GnRH pulses, leading to an increase in the LH/FSH ratio. Ibrahim and Abdelsalam [44] reported in their study that a significant increase was found in LH, testosterone and LH/FSH ratio, while FSH level was insignificantlyincreased in PCOS women. Cascella et al [45], along with another study [46],reported that the level of LH was significantly elevated in PCOS women than in the control group, while the level of FSH did not alter significantly. In another study [47], elevated levels of FSH and LH were reported in PCOS women.Elevated LH relation to FSH was also documented in PCOS women compared with control subjects [48]. Furthermore, there wasa insignificant variation (P>0.05) in LH/FSH ratio between the two groups.

Conclusion
Polycystic ovary syndrome is a frequent endocrinopathy disturbing women of reproductive age. It is the widespread reason of infertility. Moreover, more than half of the PCOS patients were obese. Based on the available data, clinicalsymptomssuch as menstrual cycle dysfunction and hyperandrogenism present with hirsutism, acne, and temporal balding were excessive in obese women with PCOS. However, the role of weight reduction is useful in the management of PCOS. This study clearly shows that the majority of patients with PCOS have high levels of testosterone and LH that seem to correlate with clinical hyperandrogenism in PCOS patients.