The Aging Male, December 2008; 11(4): 189192

Baldness, benign prostate hyperplasia, prostate cancer and androgen levels

KHAN FAYDACI1, ERYILDIRIM BILAL1, PENPEGU L NECMETTIN1, GO 1   UN ASUMAN2, & KUYUMCUOGLU UGUR TARHAN FATIH1, ORC
Urology Clinic, Lut Krdar Kartal Training and Research Hospital, Istanbul, Turkey and 2Biochemistry Laboratory, Lut Krdar Kartal Training and Research Hospital, Istanbul, Turkey (Received 6 March 2008; revised 29 July 2008; accepted 10 August 2008)
1

Abstract Introduction. We evaluated the pattern of baldness and serum androgen levels in patients with benign prostate hyperplasia (BPH) and prostate cancer. BPH, prostate cancer and androgenic alopecia (AA) were somehow androgen dependent and affect large population of elderly men. Material and method. A total of 152 patients, 108 patients with BPH and 44 patients with prostate cancer were included in the study. We measured serum total, free and bioavailable testosterone, FSH, LH, prolactin, estradiol, albumin and SHBG levels. Baldness classication was based on Norwoods classication and we categorised baldness as vertex and frontal baldness. Result. The frequency of AA in BPH and prostate cancer groups were not different. We looked for some correlation between the two groups with respect to AA and hormone levels. We did not nd any correlation between AA and total testosterone, free testosterone, bioavailable testosterone or SHBG levels in both groups. Conclusion. This prospective study with selected small group of patients showed that there is no difference of male pattern baldness in BPH and prostate cancer patients and also there is no correlation between pattern of baldness and serum androgen levels.

Keywords: Baldness, BPH, prostate cancer, androgen level

Introduction The term androgenic alopecia (AA) describes a genetically determined condition leading to permanent loss of hair in men and women. Synonyms are male and female pattern hair loss. Most men with AA show a typical pattern of hair loss, often beginning at the temples and in the vertex area [1,2]. AA and BPH occur as many as 70% of men by the age 80 and prostate cancer is one of the most common cancer diagnosed in men. Male pattern baldness is a common, androgen dependent skin problem in adult men that is not well understood. The extent of AA depends on the number of hair follicles with genetic sensitivity to androgens [3]. Studies that have specically addressed the question of whether AA is associated with prostate cancer are few, and have produced inconsistent ndings. A long-standing hypothesis is that prostatic neoplasia is stimulated by testosterone, and therefore increased androgen levels represent a risk factor for this disease [4]. A mechanism for the putative relationship between AA and BPH and prostate cancer is yet to be established.

Prospectively, we examined AA and androgen levels in a selected group of patients with prostate cancer and BPH. Then we evaluated if there was any correlation between serum androgen levels, and baldness in BPH and prostate cancer patients.

Material and method Between November 2005 and June 2006, 152 patients who underwent 12 core TRUS guided prostate biopsy because of elevated PSA values (4 ng/mL) and/or a digital rectal examination suspicious for prostate cancer were included in the study. Ages of these patients were between 50 and 75 years (mean age 66 + 0.82 years). We separated patients in two groups. The rst group was prostate cancer group and the mean age was 67.87 + 1.23. The second group was BPH group and the mean age was 65.37 + 0.65. We examined hormone levels and pattern of baldness of patients. Participants gave an informed consent about the study. Patients with the pathological diagnosis of atypical small acinar proliferation (ASAP) and high-grade prostatic

_ u mah. Madalyon sok., Madalyon apt. No: 17 D:17, Pendik/Istanbul, Correspondence: Dr. Go khan Faydaci, Dog Turkey. Tel: 90-216-3544196. Fax: 90-216-3833193. E-mail: faydacig@yahoo.com ISSN 1368-5538 print/ISSN 1473-0790 online 2008 Informa Healthcare USA, Inc. DOI: 10.1080/13685530802400995

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G. Faydaci et al. testosterone, estradiol (E2) and SHBG levels between the two groups (Table I). Total PSA, LH and FSH levels were statistically higher in prostate cancer patients (p 5 0.05). However, serum albumin level was statistically lower in prostate cancer patients (p 5 0.05). The prevalence of AA was not signicantly different between BPH and prostate cancer patients (Table II). There were no signicant differences with respect to levels of testosterone and SHBG in BPH and prostate cancer groups. We did not nd any correlation between AA and total testosterone, free testosterone, bioavailable testosterone or SHBG in either BPH and prostate cancer patients (p 4 0.05) (Table III). Discussion AA and BPH both afict a large proportion of elderly men with chronobiological progression. The response of hair follicle and prostate to androgen is different: although the former becomes miniaturised and atrophic, the prostate becomes hyperplastic and enlarged. Whether and when a scalp hair follicle miniaturises is dependent on two factors: genetics and androgens. The genes responsible for shrinkage of a scalp hair follicle are not known. Each scalp hair follicle carries individual genetic information that determines whether and when it will develop a sensitivity towards androgens. Once a scalp hair follicle has become sensitive to androgens, it will progressively shrink over the next years [6]. Because most male AA patients have normal circulating androgen levels, a local imbalance of DHT and androgen hypersensitivity in balding versus nonbalding scalps are considered to be one of the pathogenetic factors [7]. Age seems to be a confounding factor in the interpretation of androgenic effects on the hair follicle and prostate. We evaluated nearly the same age group of patients to exclude the age factor. There is little doubt that a lifetime exposure of the prostate to androgens plays an important role in prostate carcinogenesis. Long-term absence of androgen exposure to the prostate appears to protect against the development of cancer, but a dose response relationship between androgen levels and cancer risk has not been established. In particular, whether normal-low or high range androgen concentrations are associated with risk of prostate cancer remains unclear [8,9]. A more recent study from Endogenenous Hormones and Prostate Cancer Collaborative study showed that serum concentrations of sex hormones were not associated with risk of prostate cancer [10]. The strong evidence in support of a positive relationship between circulating androgen levels and prostate cancer risk comes from the longitudinal Physicians Health Study, which identied a 2.6-fold increased odds for prostate cancer for men with testosterone levels in the upper quartile and a 54% reduction in odds for prostate cancer in men with sex

intraepithelial neoplasia (PIN) were excluded from the study. In prostate needle biopsy specimens, these two histologic ndings; ASAP and high-grade PIN are each highly predictive of subsequent prostatic adenocarcinoma, and the identication of either without concurrent cancer warrants follow-up with repeat biopsy. A total of 152 individual hormone measures and hair patterns were evaluated. 44 of them were prostate cancer and 108 of them were BPH. Blood samples were obtained between 7.00 a.m. and 10.00 a.m. after an overnight fast to avoid hormonal diurnal uctuations. Serum testosterone, sex hormone binding globulin (SHBG), FSH, LH, prolactin, estradiol and albumin levels were measured. Free testosterone level was calculated with mass action equation as described by Vermeulen et al. [5]. Bioavailable testosterone was calculated with a virtual calculator that was developed at the Hormonology Department, University Hospital of Ghent, Belgium [5]. In addition, prostate volumes (PV), and total PSA values were compared with each other in the two groups (Table I). We assessed differences in age, hormone concentration and AA between prostate cancer group and BPH group. Pattern of baldness was determined during interview by a physician who did not know which group the patients belong to. Subjects were evaluated with a diagram of Hamilton classication of baldness modied by Norwood (Figure 1) [1]. We categorised AA as follows: little or no hair loss (I/II), frontal baldness (IIa/III/IIIa/IVa) and vertex baldness (III-vertex, IV/V/Va/VI and VII) (Figure 1). Data were expressed as mean + standard error. Statistical analyses were performed with Chi-square test, unpaired t test, MannWhitney test and Pearson correlation analysis by using Prism 2.01 (Graphpad software, USA). p 5 0.05 was considered signicant. Results Of the 152 examined individuals 108 were BPH and 44 were prostate carcinoma. There were no differences in age, PV, total, free and bioavailable
Table I. Comparison of the ndings between prostate cancer and BPH patients. BPH Age PV tPSA tT fT bT FSH LH Prl E2 SHBG Alb 65.37 + 0.35 61.6 + 26.6 9.0 + 7.8 545.3 + 175.0 6.8 + 7.8 229.4 + 58.7 9.6 + 7.8 7.0 + 3.7 13.7 + 8.8 27.4 + 8.1 45.65 + 24.92 4.21 + 0.42 Pca 67.87 + 1.23 51.8 + 24.9 28.0 + 30.1 524.2 + 184.8 5.9 + 4.7 209.0 + 77.3 18.3 + 24.8 11.7 + 12.1 13.8 + 10.3 26.9 + 9.1 39.47 + 15.20 4.02 + 0.48 p 0.06 0.039 50.001 0.510 0.498 0.192 0.001 0.005 0.948 0.646 0.242 0.014

Un-paired t-test.

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Figure 1. HS of baldness hair patterns as proposed by Norwood and arranged according to no baldness, vertex baldness and frontal baldness.

Table II. Hair patterning classication among prostate cancer and BPH patients. No or little hair loss, n (%) Prostate cancer BPH 6 (14%) 14 (13%) Vertex baldness, n (%) 30 (68%) 70 (65%) Frontal baldness, n (%) 8 (18%) 24 (22%)

(n 152) (p 0.338 Chi-square).

hormone-binding globulin in the upper quartile [11]. This is in contrast to the longitudinal Finnish Mobile Clinic Health Examination Survey and a variety of casecontrol studies, which nd no association between circulating androgens, SHBG and prostate cancer risk [11]. Also, Massachusetts Male Aging Study found that none of the hormones were associated with prostate cancer risk in a prospective study [12]. In our study, we found no correlation between total, free and bioavailable testosterone, and SHBG with prostate cancer and BPH. However, we

found signicantly increased gonadotropins in the Pca group (Table I). The elevated FSH and LH levels in Pca group may be an indicator for a relative testosterone deciency in Pca group. Some recent studies have suggested that low testosterone may be a risk factor for prostate cancer [13]. There is no consensus on the normal range of testosterone in the individual, however, increased gonadotropins may be a sign for a relative deciency as the pituitary gland may try to compensate for testosterone levels that may be low for these particular individuals. A link between AA and prostate cancer may be explained by aging, heritable genetic factors, or androgen metabolism; all of these are presumed to play substantial roles in both conditions [14]. Men with AA had an approximate 50% excess risk for clinical prostate cancer. The association was strongest in elderly men and blacks [15]. Association of AA with BPH or PV was shown by various studies in literature [16,17]. In addition association of AA with prostate cancer was also shown by some studies. Graham reported that their

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3. Hans W. Male and female androgenetic alopecia. In: Williams H, Bigby M, Diepgen T, Herxheimer A, Naldi L, Rzany B, editors. Evidence-based dermatology, 1st edn. London: Blackwell; 2003. pp 571576. 4. Gann P, Hennekens C, Ma J, Longcope C, Stampfer M. Prospective study of sex hormone levels and risk of prostate cancer. J Natl Cancer Inst 1996;88:11181122. 5. Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 1999;84:36663672. 6. Sawaya ME, Price VH. Different levels of 5alphareductase type I and II, aromatase, and androgen receptor in hair follicles of women and men with androgenetic alopecia. J Invest Dermatol 1997;109:296300. 7. Giltay EJ, Toorians AW, Sarabdjitsingh AR, de Vries NA, Gooren LJ. Established risk factors for coronary heart disease are unrelated to androgen-induced baldness in female-to-male transsexuals. J Endocrinol 2004;180:107112. 8. Parsons JK, Carter HB, Landis P. Higher serum free testosterone is associated with an increased risk of prostate cancer: results from the Baltimore Longitudinal Study on Aging. J Urol 2004;171:116118. 9. Platz EA, Leitzmann M, Rifai N. Sex steroid hormones and the androgen receptor gene CAG repeat and subsequent risk of prostate cancer in the PSA era. Cancer Epidemiol Biomarkers Prev 2005;14:12621269. 10. Roddam AW, Allen NE, Appleby P, Key TJ. Endogenous hormones, prostate cancer collaborative group, endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. J Natl Cancer Inst 2008;100:170 183. 11. Gann PH, Hennekens CH, Ma J. Prospective study of sex hormone levels and risk of prostate cancer. J Natl Cancer Inst 1996;88:11181126. 12. Mohr BA, Feldman HA, Kalish LA, Longcope C, McKinlay JB. Are serum hormones associated with the risk of prostate cancer? Prospective results from the Massachusetts Male Aging Study. Urology 2001;57:930935. 13. Mearini L, Costantini E, Zucchi A, Mearini E, Bini V, Cottini E, Porena M. Testosterone levels in benign prostatic hypertrophy and prostate cancer. Urol Int 2008;80:134140. 14. Olsen EA. Androgenetic alopecia. In: Olsen EA, editor. Disorders of hair growth diagnosis and treatment. New York: McGraw-Hill; 1994. pp 257283. 15. Ernest H, Rosalind AB, Barry IG. Male pattern baldness and clinical prostate cancer in the epidemiologic follow-up of the rst National Health and Nutrition Examination Survey: short communication. Cancer Epidemiology, Biomarkers Prevent 2000;9:523527. 16. Bong RO, Seong JK, Ja DM, Hyeung NK, Dong DK, Young HW, Soo BR, Yang IP. Association of benign prostatic hyperplasia with male pattern baldness. Urology 1998;51:744 748. 17. WenChieh C, Chao-Chun Y, Guan-Yu C, Meng-Chie W, Hamm-Ming S, Tzong-Shin T. Patients with a large prostate show a higher prevalence of androgenetic alopecia. Arch Dermatol Res 2004;296:245249. 18. Giles GG, Severi G, Sinclair R, English DR, McCredie MR, Johnson W, Boyle P, Hopper JL. Androgenetic alopecia and prostate cancer: ndings from an Australian casecontrol study. Cancer Epidemiol Biomarkers Prev 2002;11:549553. 19. Wendy DW, Joellen MS, Denis T, Samuel ML, Lauren M, Pamela S, David FP, Cary NR, Anderson EE, Walther PJ. Early onset baldness and prostate cancer risk. Cancer Epidemiol Biomarkers Prevent 2000;9:325328. 20. Demark WW, Lesko SM, Conaway MR, Robertson CN, Clark RV, Lobaugh B, Mathias BJ, Strigo TS, Paulson DF. Serum androgens: associations with prostate cancer risk and hair patterning. J Androl 1997;18:495500.

Table III. Comparison of hormonal levels among BPH and prostate cancer patients and correlation with AA. Prostate cancer (n 44) 524.2 + 27.85 618.5 + 45.30 519.5 + 35.78 421.9 + 59.07 5.88 + 0.72 4.580 + 0.763 6.452 + 0.940 4.546 + 2.362 209.0 + 14.87 244.5 + 18.50 207.0 + 19.66 202.6 + 15.51 39.47 + 2.92 52.00 + 7.07 38.95 + 3.41 36.56 + 6.09

BPH (n 108) Total testosterone (ng/dL) Frontal baldness Vertex baldness No baldness Free testosterone (ng/dL) Frontal baldness Vertex baldness No baldness Bioavailable testosterone(ng/dL) Frontal baldness Vertex baldness No baldness SHBG(nmol/L) Frontal baldness Vertex baldness No baldness 545.3 + 17.00 510.4 + 28.16 555.4 + 23.23 556.0 + 39.35 6.75 + 0.76 6.04 + 1.47 7.28 + 1.05 5.40 + 0.73 229.4 + 8.14 289.6 + 27.31 213.8 + 6.98 220.8 + 12.64 45.65 + 3.42 38.90 + 4.31 47.56 + 5.20 45.10 + 3.96

p 0.51 0.071 0.398 0.108 0.498 1.000 0.63 0.331 0.192 0.606 0.304 0.724 0.242 0.145 0.304 0.284

MannWhitney and un-paired t test.

data suggest an association between prostate cancer and vertex baldness; compared with men who had no balding [18]. Besides, Demark-Wahnefried reported that early onset vertex baldness is a potential risk factor for prostate cancer [19]. In some studies, the circulating free testosterone levels were demonstrated to be strongly linked to prostate cancer risk and vertex baldness, aging and heritability apparently also inuence the development of both conditions [20]. Among those with AA, a higher risk for prostate cancer was found for vertex baldness than for frontal baldness [18]. In our study, we did not observe any relationship between AA and prostate cancer or BPH for any type neither vertex nor frontal baldness. In conclusion, no signicant correlation between AA and serum androgen levels in BPH and prostate cancer patients was observed in our study with this selected group of patients. To further conrm the results, large-scale studies on the association between BPH, prostate cancer and AA with controls are needed. Declaration of interest: The authors report no conicts of interest. The authors alone are responsible for the content and writing of the paper. References
1. Norwood OT. Male pattern baldness: classication and incidence. South Med J 1975;68:13591365. 2. Whiting DA. Male pattern hair loss: current understanding. Int J Dermatol 1998;37:561566.