Baldness, benign prostate hyperplasia, prostate cancer and androgen levels

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 classification was based on Norwood's classification 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 find 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 specifically addressed the question of whether AA is associated with prostate cancer are few, and have produced inconsistent findings. 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 first 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 intraepithelial neoplasia (PIN) were excluded from the study. In prostate needle biopsy specimens, these two histologic findings; ASAP and high-grade PIN are each highly predictive of subsequent prostatic adenocarcinoma, and the identification 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 fluctuations. 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).

Table I.  Comparison of the findings between prostate cancer and BPH patients.

	BPH	Pca	p
Age	65.37 ± 0.35	67.87 ± 1.23	0.06
PV	61.6 ± 26.6	51.8 ± 24.9	0.039
tPSA	9.0 ± 7.8	28.0 ± 30.1	<0.001
tT	545.3 ± 175.0	524.2 ± 184.8	0.510
fT	6.8 ± 7.8	5.9 ± 4.7	0.498
bT	229.4 ± 58.7	209.0 ± 77.3	0.192
FSH	9.6 ± 7.8	18.3 ± 24.8	0.001
LH	7.0 ± 3.7	11.7 ± 12.1	0.005
Prl	13.7 ± 8.8	13.8 ± 10.3	0.948
E2	27.4 ± 8.1	26.9 ± 9.1	0.646
SHBG	45.65 ± 24.92	39.47 ± 15.20	0.242
Alb	4.21 ± 0.42	4.02 ± 0.48	0.014

Un-paired t-test.

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 classification of baldness modified 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).

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

Data were expressed as mean ± standard error. Statistical analyses were performed with Chi-square test, unpaired t test, Mann–Whitney test and Pearson correlation analysis by using Prism 2.01 (Graphpad software, USA). p < 0.05 was considered significant.

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 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 < 0.05). However, serum albumin level was statistically lower in prostate cancer patients (p < 0.05). The prevalence of AA was not significantly different between BPH and prostate cancer patients (Table II). There were no significant differences with respect to levels of testosterone and SHBG in BPH and prostate cancer groups. We did not find any correlation between AA and total testosterone, free testosterone, bioavailable testosterone or SHBG in either BPH and prostate cancer patients (p > 0.05) (Table III).

Table II.  Hair patterning classification among prostate cancer and BPH patients.

	No or little hair loss, n (%)	Vertex baldness, n (%)	Frontal baldness, n (%)
Prostate cancer	6 (14%)	30 (68%)	8 (18%)
BPH	14 (13%)	70 (65%)	24 (22%)

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

Table III.  Comparison of hormonal levels among BPH and prostate cancer patients and correlation with AA.

	BPH (n = 108)	Prostate cancer (n = 44)	p
Total testosterone (ng/dL)	545.3 ± 17.00	524.2 ± 27.85	0.51
Frontal baldness	510.4 ± 28.16	618.5 ± 45.30	0.071
Vertex baldness	555.4 ± 23.23	519.5 ± 35.78	0.398
No baldness	556.0 ± 39.35	421.9 ± 59.07	0.108
Free testosterone (ng/dL)	6.75 ± 0.76	5.88 ± 0.72	0.498
Frontal baldness	6.04 ± 1.47	4.580 ± 0.763	1.000
Vertex baldness	7.28 ± 1.05	6.452 ± 0.940	0.63
No baldness	5.40 ± 0.73	4.546 ± 2.362	0.331
Bioavailable testosterone(ng/dL)	229.4 ± 8.14	209.0 ± 14.87	0.192
Frontal baldness	289.6 ± 27.31	244.5 ± 18.50	0.606
Vertex baldness	213.8 ± 6.98	207.0 ± 19.66	0.304
No baldness	220.8 ± 12.64	202.6 ± 15.51	0.724
SHBG(nmol/L)	45.65 ± 3.42	39.47 ± 2.92	0.242
Frontal baldness	38.90 ± 4.31	52.00 ± 7.07	0.145
Vertex baldness	47.56 ± 5.20	38.95 ± 3.41	0.304
No baldness	45.10 ± 3.96	36.56 ± 6.09	0.284

Mann–Whitney and un-paired t test.

Discussion

AA and BPH both afflict 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 identified 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 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 case–control studies, which find 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 significantly 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 deficiency 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 deficiency 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 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 influence 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 significant 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 confirm 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 conflicts of interest. The authors alone are responsible for the content and writing of the paper.