LH/FSH, BMI and Clinical Profile in Polycystic Ovarian Syndrome: A Correlative Study

Background and Objectives: Polycystic ovarian disease (PCOS) is probably the most prevalent endocrinological disorder affecting females and is the most common cause of menstrual disturbance during the reproductive age. It is characterized by polycystic ovaries on ultrasound and/or clinical and biochemical signs and symptoms of hyperandrogenism and/or oligo- anovulation. Therefore, this study was designed to determine relationship among LH/FSH ratio, BMI and the clinical profile of females suffering from PCOS. Materials and Methods: Blood samples from 50 study subjects were taken after getting informed consent for hormone profile (FSH and LH) by ELISA kit of Kamiya Biomedical company. Body Mass index (BMI) and Ultra-sonogram related findings of polycystic ovarian syndrome patients were recorded. Statistical analysis was done by using SPSS-20. Results: LH/FSH values were significantly higher among infertile and fertile females (P=0.05). BMI was also significantly correlated statistically in female patients with and without hirsutism (P=0.005). BMI (P=0.00) and LH/FSH (P=0.004) were also found to be associated significantly with obesity in patients with PCOS. Conclusion: Since FSH was significantly correlated with obesity and infertility while BMI was associated with obesity and hirsutism among the clinical profiles, lifestyle interventions to decrease the overweight and obesity would be able to reduce the unwanted clinical symptoms of infertility and hirsutism in females with polycystic ovary syndrome.


INTRODUCTION
Polycystic Ovarian Syndrome (PCOS) is probably the most prevalent endocrinological disorder affecting females and it is the most common cause of menstrual disturbance during the reproductive age. It is characterized by presence of polycystic ovaries on ultrasound and/or clinical & biochemical signs of hyperandrogenism and/or oli-anovulation [1]. PCOS was first described by Stein and Leventhal in 1935 in women with of PCOS is multifactorial and complex. The disease has genetic basis affected by environmental factors [2,3].
Obesity is an important risk factor for PCOS. Literature review shows that 30-70% of PCOS females are obese, though disease is also seen in females of normal weight but with less frequency. The presence of obesity markedly modifies the clinical and biochemical expression of disease and makes the management of the syndrome very difficult [4].
When defined by the presence of oligomenorrhea and hyperandrogenism, 75% of women with PCOS have an LH level that is above the normal range for women in the early follicular phase and 94% have an increased LH to FSH ratio [6].
However, further studies have demonstrated an inverse relationship between LH and body weight that is continuous across a wide spectrum of body weights in PCOS patients, supporting the model of an intrinsic neuroendocrine abnormality in all oligomenorrheic PCOS patients that is modified by obesity [7,8].
Moreover, manifestations of PCOS may include menstrual irregularities, obesity and elevated serum LH levels [9].
The characteristic increase in LH relative to FSH release, have long been appreciated in PCOS. Because of the pulsatile nature of their release, a single test fails to detect an increased LH/FSH ratio. This, as well as its lack of specificity, has led to the recommendation that LH/FSH ratios not be included in the diagnostic criteria for PCOS [10,11].
Approximately half of PCOS women are obese or overweight and obesity has important role in the development of the Hyperandrogenic state [12] [13]. Even those with normal BMI, PCOS sufferers tend to have android body type with waist to hip ratio greater than 0.8 [14].
The study is designed to demonstrate a correlation/ association among LH/FSH ratio, BMI, and the clinical profile of females suffering from PCOS.

Subjects
It was a comparative study, carried out in the Department of Pathology, Allama Iqbal Medical College Lahore after approval of Ethical Review Committee. The samples were taken from Infertility clinic of Obstetrics and Gynaecology Department of Jinnah Hospital, Lahore. Purposive sampling technique was used and a total of 50 subjects were recruited for this study after an informed consent. The study included all diagnosed cases of females of reproductive age, married or unmarried presenting with clinical features of PCOS confirmed on Ultrasound. Patients with hyperandrogenism and anovulation other than PCOS like Cushing syndrome, untreated hypo or hyperthyroidism, ovarian tumors and adrenal hyperplasia/tumors were excluded from the study.
At the time of sample collection, relevant details of each participant such as age, sex, and clinical features of disease were noted. The detail about their ultrasonic findings and BMI was also noted. Samples were processed for fertility hormone profile by sandwich ELISA technique of Kamiya Biomedical Company with sensitivity of 0.48 miu/ml and high specificity without cross reactivity.
Statistical analysis: The data was entered and analyzed using IBM SPSS 20.0. Mean±SD was used for quantitative variables. Qualitative variables were expressed as frequencies, percentages and graphs. For normally distributed data one way ANOVA and for not normally distributed data Kruskal-Walis test was applied. Post Hoc Tukey test was applied to observe which group means differ in various groups. A pvalue of ≤ 0.05 was considered as statistically significant.

RESULTS
When BMI, FSH and LH were compared between fertile and infertile femles, FSH was significantly correlated with infertility shown in Table 1. When BMI, FSH and LH were compared between menstrually disturbed and undisturbed females, there was no significant difference between two groups shown in Table 2.
When BMI, FSH and LH were compared between females with hirsutism and without hirsutism, BMI is significantly associated with hirsutism shown in Table 3.
When BMI, FSH and LH were compared between females with oligomenorrhea and without oligomenorrhea, there was no significant difference between two groups shown in Table 4. When BMI, FSH and LH were compared between females with amenorrhea and without amenorrhea, there was no statistically significant difference between two groups shown in Table 5.
When BMI, FSH and LH were compared between females with menopause and without menopause, there was no statistically significant difference between two groups shown in Table 6.
When BMI, FSH and LH were compared between females with acne and without acne, there was no statistically significant difference between two groups shown in Table 7.
When BMI, FSH and LH were compared between females with and without obesity, BMI and FSH were significantly correlated with obesity shown in Table 8. When BMI, FSH and LH were compared between patients with and without regular menstrual periods, there was no statistically significant difference between two groups shown in Table 9.

DISCUSSION
In the current study, FSH, LH and BMI were compared among different groups of PCOS categorized on the basis of fertility, menstrual disturbance, hirsutism, oligomenorrhea, amenorrhea, menopause, acne, obesity and regular menstrual periods. FSH was significantly correlated with obesity and infertility while BMI was associated with obesity and hirsutism. The current study is partially in agreement with the study of Shazia Rasool et al. [18]. FSH and LH were significantly different between females with and without amenorrhea that is not similar to the current study. BMI was not significantly different between these groups that is similar to the current study.
According to Ewenighi Chinwe et al. [20] BMI, FSH and LH were statistically significant (0.000) between these groups with and without menopause that is not in accordance with current study.
The current study is in agreement with the study of Sayera Begum et al. [21] who also found no difference in LH, FSH and BMI (P>0.05). BMI (P=0.00) and FSH (P=0.04) are statistically significant between females with and without obesity but no difference is found in LH that is partially in agreement with the study of Abdulrazak et al. [16] who could not found any statistically significant difference in FSH, LH and BMI and study of Manal Ibrahim Mahmoud et al. According to Abdulrazak et al. [16] there was no statistically significant difference in LH, FSH and BMI in females with and without regular menstrual periods that is in accordance with the current study.

CONCLUSIONS
Since FSH was significantly correlated with obesity and infertility while BMI was associated with obesity and hirsutism among the clinical profiles, lifestyle interventions to decrease the overweight and obesity would be able to reduce the unwanted clinical symptoms of infertility and hirsutism in females with polycystic ovary syndrome.