The Journal of Integrated Health Sciences

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1 JIHS Available online at The Journal of Integrated Health Sciences A study of endocrine profile in premenopausal women with hirsutism Lakhani Som J 1*, Lakhani Om J 2, Raval RC 3 1 Assistant Professor, Dermatology, SBKS MIRC, Sumandeep Vidyapeeth, Piparia, Vadodara, Gujarat, India 2 1 ST year DNB, Endocrinology, Gangaram Hospital, New Delhi, India 3 Professor and Head, VS Hospital, Ahmedabad, Gujarat, India ABSTRACT Background The aim of the study was to find the endocrinal profile of patients with hirsutism presenting to dermatology OPD. Hirsutism is defined objectively by Modified Ferriman-Gallwey score 8 (mfg). Methods The study included 44 premenopausal women in whom after history and clinical examination, endocrine tests were done which included Diabetes profile, TSH, FSH, LH, Free and Total Testosterone, DHEAS, Fasting insulin,17-hydroxyprogesterone and Prolactin. Results Mean age of the patients was years while duration of symptoms was of 3 years. Upper lip was the most common site for hair growth while upper arm was the least common. Hair loss and menstrual irregularity were common associated findings. Obesity had a significant correlation with severity of hirsutism. Mean total testosterone in study patients was ng/dl. There was no correlation between severity of hirsutism and any of the endocrinal tests. Idiopathic hirsutism (IH) was the most common diagnosis, closely followed by PCOS. We detected 1 case of Non classical Congenital Adrenal Hyperplasia and no cases of Ovarian or Adrenal tumors. Serum testosterone and LH/FSH ratio were significantly elevated in PCOS group as compared to IH group. Conclusion Obesity had a strong relation with severity of Hirsutism independent of other parameters. Fasting blood sugar, serum testosterone, TSH and Fasting insulin levels had no correlation with severity of Hirsutism. Key Words: Hirsutism, Modified Ferriman-Gallwey score (mfg). Original Article INTRODUCTION: There are two types of hair on the human body, the terminal hair, which is longer, darker and coarse and the vellus hair which is fine, short and nonpigmented. Excess of vellus hair, which is seen hypothyroidism, anorexia nervosa and in some familial cases are termed as hypertrichosis. Hirsutism is defined as excessive terminal hair that appears in a male pattern (i.e., sexual hair) in women. It is defined objectively by modified Ferriman-Gallwey 8 (mfg). (1) *Correspondence: som.lakhani@yahoo.com Androgen has two effects on pilosebaceous unit. It either converts the vellus hair to terminal hair or it leads to proliferation of sebaceous gland. Hence excess of androgens leads to increase of terminal in male pattern, or male pattern baldness or increase of sebaceous secretion leading to acne. Increase of androgen in women is typically associated with hirsutism, however all cases of hirsutism are not associated with hyperandrogenism and all cases of hyperandrogenism are not associated with Hirsutism. This is because the sensitivity of pilosebaceous unit to androgen is not the same in all patients. Some patients may have normal androgens yet may have hirsutism, something which is termed as Idiopathic The Journal of Integrated Health Sciences Vol 2 Issue 2 December

2 hirsutism and others may have increased androgen and no hirsutism, which is termed as Cryptic hirsutism. (2) Hirsutism is a common problem in patients attending both dermatology and endocrine OPD. In this study we have evaluated the Hormonal profile in Premenopausal women with hirsutism attending the OPD of our institution. METHODS This cross-sectional, prospective study was conducted from June 2011 to August 2013 within a span of 2 years and three months amongst patient attending the Dermatology OPD of V.S. General hospital, Ahmedabad. Institutional ethics committee permission was granted for the study. Inclusion Criteria: 1. The patient having clinical features of hirsutism. Hirsutism was defined as per modified Ferriman-Gallwey score>=8 Table 1. Hormonal tests done in patients with hirsutism Fasting and Postprandial Blood sugars Fasting Insulin level with HOMA-IR calculation* TSH Serum Testosterone level SHBG with Free Testosterone calculation* 17 Hydroxyprogesterone level (17 OHP) S. DHEAS S. Prolactin S. FSH S. LH (* Fasting Insulin, SHBG and Free testosterone was not done in all patients due to non availability of test in hospital. It was done in selected patients based on clinical judgement) Exclusion Criteria: 1. Patients on drugs which would modify the hormonal pattern and profile of patients were excluded. This includes insulin sensitizers, anti androgens and other hormonal treatment. 2. Pregnant and lactating mothers were excluded from the study. 3. Post menopausal women After clinical history and examination, the hormonal tests were done in all patients included in the study (Table 1). The interpretation of result was done in consultation with endocrinologist. Apart from this additional testing was done depending on the diagnosis suspected. Those suspected to have Polycystic ovary syndrome (PCOS) additionally underwent ultrasound during the follicular phase of menstrual cycle. Tests 4,5,6, 7, 8 and 9 were done in the follicular phase in menstruating women. BMI=weight in kg/height(m)2 The patient was considered to be underweight, normal, overweight or obese according to south Asian BMI standards which is as follows (3) : BMI in Kg/m 2 Inference <18.5 Underweight normal overweight >25 obese Modified Ferriman& Gallwey semiquantitative scoring for hirsutism was adopted for this study The nine body areas which included upper lip, chin, chest, abdomen, pelvis, upper arm, thighs, upper back, and lower back were examined. These are the areas considered to be androgen sensitive. They were graded from 0-4. If no terminal hair was observed it was considered to be 0, and if frankly virile pattern of hair was seen it was graded to be 4. Minimum possible score was zero and maximum was 36. A score of less than 8= no hirsutism, 8-16 = mild hirsutism, = moderate hirsutism, greater than 25 = severe hirsutism (4) Rotterdam criteria was used to define PCOS. (Table 2). Non classical Congenital adrenal hyperplasia was suspected in patient with elevated 17 The Journal of Integrated Health Sciences Vol 2 Issue 2 December

3 hydroxyprogesterone (17 OHP) and confirmed with ACTH stimulated 17 OHP. In patients having very high DHEAS or testosterone, appropriate imaging was done to rule out Adrenal or Ovarian neoplasm. Idiopathic hirsutism was a diagnosis of exclusion and was defined in patients with hirsutism but no menstrual irregularity and normal androgen levels. American Diabetes association criteria were used to defined Diabetes mellitus, impaired fasting glucose and Impaired glucose tolerance. Table 3 shows the other laboratory cut offs and criteria used in the study Table 2. Rotterdam criteria for PCOS (1) To define PCOS patient should have any two of three features 1. Clinical or Biochemical evidence of Hyperandrogenism (Hirsutism, Acne, Androgenic Alopecia or elevated Serum androgen results) 2. Clinical features of Anovulation ( Oligomenorrhea or less than 6-9 Menses per year ) 3. USG features a. a. Ovarian volume >10 mm 3 b. b. OR 12 or more follicles measuring 2-9 mm in size Statistical analysis Statistical analysis was done using IBM SPSS software v Student s t test was used for parametric data. Pearson s correlation was used for finding strength of association between variables. P value of <0.05 was considered significant and <0.01 was considered highly significant RESULTS The mean age of the study group patients was 25.45± 9.06.We had included only premenopausal women. Age had no correlation with severity of Hirsutism. Maximum members of the study population were in the age range between years of age. The majority of the patients in our study were Hindus (54.55%).Family history of Hirsutism was found to be more in Muslim patients as compared to Hindus. The mean duration of hirsutism in our study was 3.29 yrs. The majority of the patients (56.82%) in our study had duration of 3 years or more. This could be attributed to the fact that none of our patient had tumors of the adrenals or ovaries which has a much more acute presentation of hirsutism. The maximum severity of growth of hair was present in the upper lip, lower abdomen and chin area and the mean score in these areas was 1.81, 1.79 and 1.75 respectively. Upper arm was the least common site of hair growth with mean mfg score of only 0.11.According to Sharma et al the chin showed maximum mfg score followed by upper lip. Knochenhauer et al (5) concluded that a score of >2 in either chin or lower abdomen detected all hirsute women, although the author emphasized this finding to be of low positive predictive value and hence more relevant to areas with high frequency of hirsutism. The majority of our patients had mild hirsutism (95.45%) but none had severe hirsutism. This could be due to the fact that none of our patients had any tumor of the adrenals or ovaries which produces severe hirsutism. We examined type, length, texture, colour and other characteristics of hairs also, apart from distribution to differentiate Hypertrichosis from Hirsutism. The most common associated cutaneous manifestations in patients of hirsutism were hair loss followed by acne. The prevalence of acne in our study was 15 (34.09%) of 44 patients. According to Chabbra et al (6) it was found in 22(55%) of 40 patients. Sharma et al (7) had an acne prevalence of 60%. Menstrual irregularity was found in 45.45% in our study while it was 40% in the study done by Chhabra et al. (6,7) Hair loss was found in 20 patients (45.45%) in our study while it was found to be 27.5 percent according to Chhabra et al (6) This greater number could be explained by the fact that Chhabra et al (6) had included only androgenetic alopecia whereas we had included all cases of hair loss including telogen effluvium which has significant endocrinal correlation. The Journal of Integrated Health Sciences Vol 2 Issue 2 December

4 Table 3. Laboratory cut off used for various tests in this study Blood Glucose-Fasting Hemoglobin A1C Total Testosterone Blood Glucose-Post- Prandial (PPBS). Normal Levels Inference Remarks mg/dl 100 IFG 126mg/dl- Diabetes mellitus FBS after overnight fast PPBS 140 mg/dl IGT Done 2 hr after 75gm 200 mg/dl - DM Glucose load 4-5.6, =prediabetic 6.5=DM 1-66 ng/dl >66 ng/dl- elevated in Females Cut off For Females >12 yrs of age Free Testosterone = borderline,>1.9 = Cut off For Females >12 < 0.7 ng/dl (Calculated) Hyperandrogenism in females yrs of age LH 2-15 miu/ml FSH 3-20 miu/ml LH/FSH RATIO < 1 >1 i.e. Reversed ratio=significant >2 = seen in PCOS >16.8 S/O PCOS related Fasting Insulin 6-27 micro IU/ml hyperinsulinemia(ref.)raised after 1hr of 75gm gluose Fasting ingestion Fasting GI Ratio S/0 I.R. FBS/FASTING INSULIN HOMA-IR* 1.55 (49,50) More suggest degree of IR FBSxFI/405 TSH µiu/ml TSH > 5.5 with Normal T3 AND T4- s/o of Subclinical hypothyroidism TSH > 5.5 with Low T3 AND T4- s/o of Overt hypothyroidism T3 (total) ng/ml T4 (total) µg/dl DHEAS < 395 µg/dl Prolactin ng/ml Suspected CAH if elevated 17 OH progesterone nmol/l (Confirmed with ACTH stimulation test) Though majority of patients came to dermatology significant correlation between severity of Hirsutism outpatient department for seeking opinion as well as measured by Modified Ferriman-Gallwey and consultation for their hirsutism problem as well as cosmetic treatment, menstrual irregularity was one of Obesity i.e. more obese patients were having more severe hirsutism. (p <0.01). the most important accompaniments. Menstrual irregularity was present in all PCOS patients. Anovulation is considered as one of the important criteria to diagnose PCOS. Of 44 patients, 26 were normal, 10 were overweight and 8 were obese. Thus 18 (40.9%), were either overweight or obese. We found a statistically % patients of hirsutism had normal fasting blood sugar (FBS) levels. 11 patients had impaired glucose tolerance and 3 had FBS, in the diabetic range. Thus hirsutism could prove to be a clue to diagnosis of early diabetes as many patients (25%) fell in the IGT range. Correlation between FBS level The Journal of Integrated Health Sciences Vol 2 Issue 2 December

5 and severity of Hirsutism was not statistically significant. 8 patients of PCOS (47.05%) patients had impaired fasting glucose (IFG). 4 patients (21.05%) of idiopathic hirsutism (IH) patients also had impaired fasting glucose (IFG). According to Unlühizarci K et al there are not enough data showing whether patients with IH also have insulin resistance, so further investigations are required regarding the same. PP2BS was in diabetic range in 3 patients and in impaired range in one patient. Free insulin could be done only in 11 patients of whom 5 had PCOS. On calculating HOMA-IR, all 11 patients had insulin resistance, if the cut off is taken as Majority(72.73%) patients had HOMA-IR of less than 2.62.There was no clinical correlation between Free Insulin levels and severity of hirsutism (p = 0.91) Total testosterone was raised in 11 out of 44 patients (25%).10 out of 11, who had raised total testosterone were having PCOS and one had Non Classical CAH. Mean total testosterone in study patients was ± We found no statistically significant correlation between obesity and Serum testosterone levels. Correlation between serum testosterone level and irregularity of menstrual cycle was highly significant (p <0.01). There was no significant correlation between severity of Hirsutism and Serum testosterone levels. All patients with elevated testosterone were diagnosed to have PCOS based on the Rotterdam criteria. 62% of patients with PCOS had elevated testosterone levels. Age had a negative correlation with Serum testosterone level i.e. patients with older age had less testosterone level and vice versa. Free testosterone was calculated from S. Testosterone and SHBG values. Since the test was not available in house it was done in only 10 patients. Mean level was 1.087ng/dl. In 2 patients calculated free testosterone was high. There was no statistically significant correlation between severity of Hirsutism and Free testosterone level. 5 patients had elevated DHEAS level of which 4 had PCOS and 1 had Non Classical CAH. The DHEAS levels were elevated in 11.36% of patients of hirsutism. TSH was above normal in 4 and normal in 40. All of these 4 patients had hypothyroidism. There was no correlation between TSH level and Severity of Hirsutism. LH/FSH ratio was 1 in 17 patients of which 14 had PCOS. The mean LH in our study was 5.98, mean FSH was 5.55 and the mean LH: FSH ratio was The ratio in patients with PCOS patients was 1.89 which was greater than in the IH group (0.75). This was statically significant. In 25% of patients the LH: FSH ratio was raised (greater than 1), while it was abnormally high (>2) in 13.64% of patients. Thus a total of 38.64% patients had an altered LH: FSH ratio. Increased prolactin was present in 21.05% patients of with hirsutism. None of the patient having high prolactin were found to have Prolactinoma. No patient had prolactin value >30 ng/ml. Hence the prolactin elevation was only mild. We found no statistically significant correlation between severity of Hirsutism and Serum prolactin value. When the final diagnosis was assessed, 46%of patient fulfilled the criteria for PCOS, while 53.5% of patients were labelled as Idiopathic hirsutism. 1 patient was diagnosed to have Non Classical CAH. No patient was found to have Adrenal or ovarian neoplasm. When the groups labelled as PCOS were compared with Idiopathic hirsutism we found that patient with PCOS has higher mean Total testosterone than patients with IH. We found that LH/FSH ratio was significantly higher in patients with PCOS as compared to IH. The difference in mean mfg values, BMI,TSH, FBS and S. DHEAS were not different in the two groups. (Table 4) DISCUSSION Hirsutism is a common complaint in premenopausal women. Our study found that Idiopathic hirsutism as the most common cause of hirsutism, closely followed by PCOS. Most cases of hirsutism tend to be mild. Obesity was strongly associated with severity of Hirsutism and as a corollary weight loss may be one effective way of reducing the severity of hirsutism. However, there was no statistically The Journal of Integrated Health Sciences Vol 2 Issue 2 December

6 significant correlation between testosterone levels, fasting blood sugar or fasting insulin levels and Table 4. Difference between patients with idiopathic hirsutism and PCOS. IDIOPATHIC HIRSUTISM PCOS Percentage 53.5% 46% P VALUE Age P= Mean mfg score Obese or overweight P= % 27% P = Mean FBS 89.6 mg/dl mg/dl Mean Total testosterone 48.5 ng/dl 77.1 ng/dl P= P = TSH P = 0.37 Mean LH/FSH Ratio Mean S. DHEAS P < ug/dl 227 ug/dl P = 0.95 severity of hirsutism. LH/FSH ratio and serum testosterone levels were significantly higher in subgroup of patients who had PCOS compared to those who idiopathic hirsutism (as it is expected based on the disease definition). However the prevalence of obesity was not different in patients with IH and PCOS. Hence we believe that obesity may have some unexplained relation with hirsutism beyond the realm of Insulin resistance. A holistic treatment aimed at finding the underlying endocrinal dysfunction and treatment of the same could achieve better results rather than performing cosmetic procedures like laser hair reduction alone. Strengths and Limitations of the study Our study can be a good primer for future studies exploring the endocrinal aspects of hirsutism amongst Indian patients. Our study is limited by small representative size. CONCLUSION Our study was done to explore the endocrinal aspects of patients presenting with hirsutism. We found that idiopathic hirsutism was the most common form of hirsutism. Obesity had a strong relation with severity of hirsutism independent of other parameters. Fasting blood sugar, serum testosterone, TSH and fasting insulin levels had no correlation with severity of hirsutism. REFERENCES 1. Rosenfield RL. Clinical practice. Hirsutism. N Engl J Med2005 Dec 15;353(24): Barnes R, Ehrmann D, Rosenfeild R. Hyperandrogenism, Hirsutism & PCOS. In: Krester D, Grossman A, editors. Endocrinology Adult & Pediatric. 6th Edition ed ed: Saunders Elsevier; WHO expert consultation. Appropriate bodymass index for Asian populations and its implications for policy and intervention strategies.lancet 2004; 363: Ferriman D, Gallwey JD. Clinical assessment of body hair growth in women. J Clin Endocrinol Metab Nov;21: Knochenhauer ES, Hines G, Conway-Myers BA, Azziz R. Examination of the chin or lower abdomen only for the prediction of hirsutism. Fertil Steril2000 Nov;74(5): Chhabra S, Gautam RK, Kulshreshtha B, Prasad A, Sharma N. Hirsutism: A Clinico-investigative Study. Int J Trichology2012 Oct;4(4): Sharma NL, Mahajan VK, Jindal R, Gupta M, Lath A. Hirsutism: clinico-investigative profile of 50 Indian patients. Indian J Dermatol2008;53(3): The Journal of Integrated Health Sciences Vol 2 Issue 2 December