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Clinical Practice Patterns of Polycystic Ovary Syndrome Among Doctors of Different Specialties—An Indian Perspective

1. Department of Endocrinology, Center for Endocrinology Diabetes Arthritis & Rheumatism (CEDAR) Superspecialty Clinics, New Delhi, India; 2. Department of Endocrinology, Max Superspecialty Hospital, Patparganj, New Delhi, India; 3. Department of Endocrinology, Maharaja Agrasen Hospital, Punjabi Bagh, New Delhi, India; 4. Department of Endocrinology, Apex Plus Superspeciality Hospital, Rohtak, India; 5. Department of Endocrinology, Kalpavriksh Superspecialty Center, Dwarka, New Delhi, India; 6. Department of Endocrinology, Manipal Hospitals, Dwarka, New Delhi, India; 7. Department of Endocrinology, Gangaram Bansal Superspecialty Hospital, Sri Ganganagar, India; 8. Department of Endocrinology, Bharti Hospital, Karnal, India

Polycystic ovary syndrome (PCOS) is a common hormonal, lifestyle, and metabolic disorder, managed by a diverse team of doctors, such as endocrinologists, gynecologists, dermatologists, and internists, depending on the predominant clinical phenotype and the age of presentation of the individual. 1 Often, there is a lack of coordination between doctors of different specialties, and often the same clinical phenotype may be managed differently by the doctors of different specialties. 2 This may lead to patient dissatisfaction, confusion, and even depression. 2

Study participants
Study participants were a diverse group of practicing doctors ranging from family physicians, internal medicine specialists, gynecologists, pediatricians, and endocrinologists practicing in New Delhi who voluntarily chose to attend the conference. The venue, timing, and the program content of the conference was advertised in the local newspapers, radio, and all major hospitals of the respective cities for 3 months prior to the actual event.
We calculated "weighted percent value" to establish the frequency at which doctors ordered a particular investigation, selecting a particular treatment option, or disease profile with managing PCOS. For questions that had the option to select a particular percentage range (<10%, 10-25%, 25-50%, 50-75%, and >75%), a weighted percent value was calculated by multiplying the median value of each of the percent range with number of participants choosing that option, then adding them up for all the five options, and lastly calculating its mean. For <10%, a median value of 5.0 was considered for calculation; for 10-25%, a median value of 17.5 was considered for calculation; for 25-50%, a median value of 37.5 was considered for calculation; for 50-75%, a median value of 62.5 was considered for calculation; and for >75%, a median value of 87.5 was used for calculation. This method was used for comparing the management preferences of doctors from different specialties for questions 9-13 and 15-20. The weighted percent value was calculated as the sum of the product of the median of each range with number of doctors selecting that option, and then finding the mean of that for a particular specialty by dividing the sum value with number of doctors of that particular specialty who selected the option. For example, the weighted percent value with regards to frequency of testing for serum 17OHP as a part of PCOS work-up among general physicians was 24.92%. This was achieved by finding the sum of 5 x 70 (number of physicians selecting option A) + 17.5 x 96 (number of physicians selecting option B) + 37.5 x 58 (number of physicians selecting option C) + 62.5 x 10 (number of physicians selecting option D) + 87.5 (number of physicians selecting option E) which came to 6,580. The mean of 6,580 for the 264 physicians is 24.92%.

Statistical analysis
Summary statistics were prepared for responses to each question.
Because not every participant answered all questions, the percentage of respondents providing a given answer was calculated individually for each question, using the number of respondents to that question as the denominator. The analysis was performed using the Statistical Package for the Social Sciences (SPSS) (Chicago, IL, USA) version 20.

Results
A total of 695 questionnaires were distributed to the doctors with their conference kit, at the reception area of the conference. From a total of 538 completed questionnaires that were collected (77.41%), 417 questionnaires (60.00%), which fulfilled all criteria, were analyzed. Questionnaires where <80% of the questions answered (n=121) were excluded from analysis.
Of the doctors who answered the question on PCOS and obesity (n=369), 171 doctors (46.34%) felt that 25-50% of women with PCOS had associated obesity.
Polycystic ovary syndrome biochemical-hormonal and radiological evaluation Overall if we look at the preference for different investigations in the diagnostic work-up of patients with PCOS, the most popular investigation was abdominal ultrasound (n=360), followed by hormone analysis (n=314), blood glucose testing (n=285), dyslipidemia (n=188), and liver function test (n=138) (see Table 1). Polycystic ovary syndrome treatment practicesvariation among different specialties 17OHP testing was most commonly ordered by endocrinologists, followed by the general physicians, and least by the pediatricians, which was statistically significant. There was no significant difference in DHEAS and insulin testing among doctors of different specialties. Screening for dysglycemia and dyslipidemia was most commonly performed by endocrinologists, followed by general physicians, and most infrequently by doctors of other specialties and it was statistically different. The use of estrogen + progestogen combination pills for the treatment of PCOS was statistically different among

Original Research Reproductive Endocrinology
US ENDOCRINOLOGY groups, with highest being in endocrinologists. Use of spironolactone as an anti-androgen was also statistically different among groups, with the highest use by endocrinologists, followed by gynecologists. Finasteride use as an anti-androgen was low and similar between the groups. The use of short-term progestogen was significantly different among groups, with the highest level among gynecologists for women with oligomenorrhea. The use of metformin was highest among endocrinologists, followed by general physicians, and was lowest in doctors of other specialties. Detection of depression in girls living with PCOS was highest by pediatricians. Weighted percent value can be seen in Table 2.

Discussion
Our study reiterated that PCOS is predominantly a disease of young women; peak age of diagnosis was reported to be 18-30 years in our study, noted by 63% of the doctors. Menstrual irregularity, hirsutism, weight gain, infertility, and acne were the top five signs and symptoms noted by doctors which lead to the diagnosis of PCOS. Obesity is being increasingly documented in PCOS. 1,4 This is supported by the observation that the majority of the doctors in this study felt their patients with PCOS had associated obesity. Positive family history of PCOS was not commonly noted in patients with PCOS.
In a population-based study screening 2,400 women from Haryana, India, the prevalence of PCOS was observed to be 4.21%, with 71% patients being from urban populations. 5 Biochemical hyperandrogenism was the most common phenotype among people living with PCOS (64%), followed by menstrual irregularities (52%), ultrasound appearances of polycystic ovaries (35%), and clinical hirsutism (30%). 5 All the three features of polycystic ovaries, along with clinical hirsutism and biochemical hyperandrogenism, were present in only 19% patients. 5 In a multi-country study evaluating racial and ethnic differences in the prevalence of metabolic syndrome in people with PCOS, women from India had the highest mean Ferriman-Gallwey score for clinical hyperandrogenism, age-adjusted odds ratio for metabolic syndrome was highest in African-American women. 6 Screening for NCCAH using 17OHP and hyperandrogenism was low among doctors in this study. Only 6.24% doctors routinely screened for serum 17OHP to rule out NCCAH in their practice. Endocrinologists were most likely to screen for NCCAH among doctors of different specialties. Uliassi et al. also noted that endocrinologists were more likely to screen for serum morning cortisol and congenital adrenal hyperplasia compared to general physicians and the gynecologists. 7 Hence, there is a need to increase awareness among doctors managing patients with PCOS with regards to NCCAH. DHEAS testing was quite popular with regards to screening for biochemical evidence of hyperandrogenism. DHEAS is typically a measure of the degree of adrenal hyperandrogenism, whereas serum testosterone is a measure of ovary-associated hyperandrogenism. 8 Screening for dysglycemia (fasting glucose and/or HbA1c) was much more frequent than screening for biochemical evidence of hyperandrogenism.
Endocrinologists and general physicians were most likely to screen for dysglycemia and dyslipidemia among doctors of different specialties. Uliassi et al. also noted that endocrinologists and generalists/physicians were more likely to order lipid profile evaluations in women with PCOS. In their study of prescription records, 60% of endocrinologists and generalists/physicians ordered lipid profile tests for their patients with PCOS, compared with none by the gynecologists. 7 This is especially relevant from an Indian perspective, in view of the high prevalence of both prediabetes (11-14%) and diabetes (9-11%) among Indians. 9 Indians develop type 2 diabetes nearly 2 decades earlier than the western world, with peak incidence around 30 years of age, when PCOS prevalence is also fairly high in women. 10 Nearly one-quarter Spironolactone was the most popular anti-androgen used to manage PCOS in our study. Use of finasteride as an anti-androgen was low across doctors from all specialties. This is in accordance with treatment practices in USA. 17 In the USA, spironolactone is the most popular anti-androgen, followed by finasteride, flutamide, and dutasteride. 17 In the current study, endocrinologists and gynecologists were the two groups of doctors who are most likely to use anti-androgens for managing PCOS. Metformin use was common among doctors managing PCOS, with more than 50% of doctors in this study frequently using metformin in their practice. Metformin has been found to be beneficial both in lean and obese patients for reducing the symptoms of PCOS, in conjunction with oral contraceptive pills and anti-androgens. 17 Metformin for PCOS was more commonly prescribed by endocrinologists, compared with other specialties in the study by Uliassi et al. 7 The chronic nature of PCOS, associated with altered physical appearance (excess body hair, acne, obesity, metabolic syndrome), menstrual irregularities, and infertility may lead to depression is some patients. 4 In our study, depression was commonly noted by one in three doctors in their patients living with PCOS. Depression was most likely to be picked up by pediatricians in our study, highlighting that it may be a significant problem in young girls with PCOS in their teenage years. In a meta-analysis involving 12 studies where depression was primarily assessed (910 women with PCOS and 1,347 controls) and six studies where anxiety was primarily assessed (208 women with PCOS and 169 controls), both the mental health manifestations were found to be associated with PCOS. 18 Women with higher body mass index had worse depression and anxiety scores. 18 In a study from the USA evaluating treatment practices in adolescent patients with PCOS, gynecologists were more likely to order pelvic ultrasonography than pediatricians and endocrinologists, whereas metformin use was highest by endocrinologists, followed by gynecologists and pediatricians, highlighting that heterogeneity in PCOS treatment practices is a global phenomenon. 19 It must be highlighted that the low participation of endocrinologists in the study cohort is reflective of the small number of endocrinologists in clinical practice in India, compared with doctors from other specialties. 20 To summarize, this is the first study, to our knowledge, to evaluate the treatment practices in women living with PCOS by doctors of different specialties in India. Screening for NCCAH in people living with PCOS is rare in India. Endocrinologists and gynecologists are more likely to use hormone pills to manage PCOS. Metabolic complications of PCOS are more likely to be screened by endocrinologists and general physicians. As depression was detected more frequently by pediatricians, this indicates that depression is more likely to be faced by young girls with PCOS. There is an urgent need for more interaction and collaboration among gynecologists, endocrinologists, pediatricians, and general physicians to homogenize and standardize the treatment practices in India. q