Hormonal profile in Indian men with premature androgenetic alopecia.

INTRODUCTION: Alopecia in male is considered as a genetically determined disorder characterized by increased level of local androgen metabolite and increase androgen receptor binding in balding areas. Frequent deviations of hormones from normal values have been reported in men diagnosed with premature androgenetic alopecia (AGA) especially for androgens, gonadotropins and sex hormone binding globulin (SHBG). Different studies in the past have inferred that premature baldness before the age of thirty in males could be considered equivalent to the polycystic ovary syndrome (PCOS) in female.
MATERIALS AND METHODS: Hormonal profile of 50 men with severe premature balding before 30 years of age were compared with same numbers of age matched controls. The serum concentrations of total testosterone, dehydroepiandrosterone sulfate, luteinizing hormone, follicle stimulating hormone, SHBG, insulin and fasting blood sugar were estimated. Statistical analysis was performed with paired Student's t-test for cases and controls.
RESULTS: Decreased levels of SHBG with high free androgen index were found in cases when compared with the controls.
CONCLUSION: Though altered hormonal profile may coexist in some of men with premature AGA it can't be considered as male equivalent to PCOS in female or the metabolic syndrome.

INTRODUCTION

Androgenetic alopecia (AGA) is considered as a genetically determined disorder characterized by increased level of local androgen metabolite and increased androgen receptor binding in genetically predisposed men.[1] AGA developed before 30 years of age and reached at least stage 3 of Hamilton-Norwood classification is termed as premature AGA.[2] Premature AGA not only adds to psychological stress but also reported as the risk factor of carcinoma prostate[3] cardiovascular diseases[4] and metabolic syndromes.[5]

Estimation of serum hormones is essential for management of AGA and hirsutism in females. Abnormality of hair distribution like alopecia or marked hypertrichosity is commonly observed in the first line relatives of women suffering from the polycystic ovary syndrome (PCOS).[67]

PCOS is a multifactorial disorder that leads to hormonal and metabolic imbalance with autosomal dominant trait of transmittance in female.[89] PCOS is characterized by the coexistence of anovulation and hyperandrogenism in the form of hyperandrogenemia, high free androgen index (FAI), low follicle stimulating hormones (FSH), high luteinizing hormone (LH) and insulin resistance.[9] The previous studies have revealed the association of premature AGA in men with decreased levels of sex hormone binding globulin (SHBG), high FAI and insulin resistance. Disproportionate levels of serum gonadotrophins like low FSH, high LH have been demonstrated in some men with premature AGA.[7101112]

Considering autosomal dominant nature of PCOS in females, it has been suggested that same can be expressed in males as a premature AGA.[12] With reference to similarity of hormonal profiles of men with premature AGA and PCOS in female, hypothesis of existence of a male PCOS equivalent in men with premature AGA was put forward and tested in various studies.[7101112] Most of these studies have been conducted outside India, hence we intended to study the hormonal profile in Indian men with premature balding.

MATERIALS AND METHODS

A case-control study approved by the Institutional Ethics Committee was carried out at NKP Salve Institute of Medical Sciences and Lata Mangeshkar Hospital, Nagpur from August 2010 to July 2012. A total of 50 males below the age of 30 years with premature balding (with alopecia defined as grade 3 vertex or more) attending Dermatology outpatient department (OPD) of our institute were included. Classification scale of Hamilton with Norwood was used for grading of AGA.[13] Equal number of age matched controls were selected from patients attending dermatology OPD. The patients and controls having endocrine or immune diseases, on steroid medication over the previous 3 months, obesity or having other causes of alopecia were excluded from the study.

Basal blood samples for determination of hormonal and biochemical parameters were taken between 7 a.m. and 8.30 a.m. after overnight fasting. A volume of 5 ml of venous blood was collected in the plain bulb and 1 ml of blood was collected in a fluoride bulb. Blood samples were centrifuged at 1509 g. Fasting blood sugar was estimated by Glucose Oxidase-Peroxidase method on fully automated analyzer Selectra E®. The serum was frozen at − 20°C for analysis. Serum total testosterone, dehydroepiandrosterone sulfate (DHEA-S), LH, FSH and Insulin were estimated on Lumax® analyzer by Chemiluminance technique using Acculyte® CLIA micorwells and Kit (Lilac medicare™). SHBG was estimated by ELISA method (Diasource® kit).

Statistical analysis was performed with Student's ‘t’-test and P < 0.05 was considered to be significant.

RESULTS

The entire participants of the study were below 30 years of age. Cases were in the age group of 21-29 years with a mean age of 25 years while age group of control was from 21 to 28 years with the mean of 24 years. Average grade of AGA was grade III vertex in cases while all controls chosen had normal hair line.[13] Hormonal profile of all controls was within standard limits (according to literature of a kit) while hormonal profile of cases showed some deviation from the normal levels. Fasting blood glucose was normal in all cases and controls.

When compared with control there was no statistically significant difference found in serum total testosterone, DHEA-S, FSH, LH and Insulin levels. Half of the patients showed SHBG levels lower than its reference range and its levels were decreased significantly in cases when compared with the control. FAI = Total Testosterone/SHBG × 100 found to be significantly higher in cases than the controls (P = 0.0006). Fasting blood sugar and serum insulin levels were normal in cases as well as in controls. Fasting glucose insulin ratio (FGIR) i.e. ratio of fasting blood sugar to the insulin levels was calculated to estimate insulin resistance. There was no statistically significant difference found in FGIR of cases and controls [Table 1].

Table 1

Comparisons of serum hormones levels between cases of premature AGA and controls

DISCUSSION

AGA is the most prevalent form of alopecia in men having polygenic origin. Total testosterone levels were within normal levels did not change in cases and controls. Some of the cases had low levels of SHBG than the reference range and level. were decreased significantly when compared with the controls (P = 0.007). Frequently lower levels of SHBG were attributed to the higher frequency of the polymorphism of D327N of the SHBG gene in these men.[14] While further studies have reported androgen receptor gene present on X chromosome as well as mutations in P2RY5 display variable expressivity was a factor underlying both hypotrichosis and alopecia.[15] Although testosterone levels were normal, FAI was significantly higher in cases than controls (P = 0.0006). Free testosterone accelerates gradual transformation large terminal scalp follicles to tiny villous ones causing premature AGA in genetically predisposed person.[16] This shows that FAI is the best marker of a person's androgen status as it can bind to tissue receptors.

Our results are in accordance with studies conducted in the past.[10111217] PCOS is another common cause of elevated serum DHEA-S levels in women.[18] Though serum DHEA-S is the weak androgen, it functions as a precursor for more potent androgen such as testosterone and dihydrotestosterone (DHT). We found serum levels were normal in both groups. Our finding resembles to previous studies[10111219] however skin concentration and urinary excretion of DHEA-S was found to be increased in few studies.[2021] Hence we support the established fact that premature AGA is not only induced but its chronic course is maintained by the increased local concentration of potent androgens mainly DHT, synthesized from circulating testosterone.

Although androgen profile of men with premature AGA simulate to the hormonal profile of ovarian follicular phase of females, we could not demonstrate changes in pituitary hormones like LH and FSH unlike in previous studies.[1822] The present study could not demonstrate insulin resistance in both groups. Insulin resistance was consistently associated with premature AGA in most of the studies conducted in past.[101112141923] This does not correlate with findings of our study as patients were non-obese and were < 30 years of age. Our results could be reinforced by past studies which have correlated insulin resistance with aging[2324] and obesity[25] more than AGA.

To summarize we could state that in spite of normal levels of total testosterone in balding men, lower levels SHBG reveals genetic susceptibility for the action of free testosterone in balding men. However it does not fulfill all criterions corresponding to PCOS in females like hyperandrogenism, altered pituitary hormones and increased insulin resistance. Even it couldn’t be considered as an expression of metabolic syndrome X due to the absence of insulin resistance which is commonly found in males.[25] Instead same hormonal changes have been observed in females with androgenic alopecia except normal SHBG levels.[26] From the present study, we could conclude that premature AGA might be considered as a separate entity and could not be considered as male PCOS equivalent. Previous studies which found possible equivalence of premature AGA in males to PCOS in females were done in non-Indian population. As our study is limited to Indian population equivalence of premature AGA in men with PCOS in female can’t be completely ruled out considering the importance of genetic predisposition. Hence further collaborative studies of larger sample size and with the follow up of hormonal profiles in forties and fifties are needed. We also propose that exact identification of the male PCOS phenotype might be determined by genetic studies.