Steroid 5α-Reductase Deficiency in Man: An Inherited Form of Male Pseudohermaphroditism

Imperato‐McGinley, Julianne; Guerrero, Luis; Gautier, Teófilo; Peterson, Ralph E.

doi:10.1126/science.186.4170.1213

Cited by 1,194 publications

(499 citation statements)

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“…[30][31][32][33] A role of androgens in risk of BPH is also supported by the absence of BPH in men castrated before puberty, 34 and by the absent or small prostate in men deficient in 5a-reductase type 2. 35,36 Pharmacological inhibition of dihydrotestosterone, a testosterone metabolite present in the prostate, is associated with a reduction in prostate size, urinary symptoms and surgery for BPH. 37,38 In the Health Professional Follow-up Study, men who had surgery of BPH had lower androstanediol glucoronide levels (a precursor of dihydrotestosterone) and higher estradiol levels.…”

Section: Discussionmentioning

confidence: 99%

History of weight and obesity through life and risk of benign prostatic hyperplasia

et al. 2005

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OBJECTIVE:The relation of anthropometric measures, diabetes, hypertension and hyperlipidemia with benign prostatic hyperplasia (BPH) risk was investigated. DESIGN: Hospital-based case-control study. SUBJECTS: Cases were 1369 men with histologically confirmed BPH, and controls were 1451 men below 75 y, admitted to hospital for acute non-neoplastic diseases. MEASUREMENTS: Using a structured questionnaire, trained interviewers collected information on self-reported height and weight, and measured waist and hip circumference of patients. The odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional multiple logistic regression models. RESULTS: Compared to the corresponding lowest quartile, the OR for the highest one were 0.76 (95% CI 0.59-0.98) for body weight, 0.71 (95% CI 0.54-0.94) for waist-to-hip ratio and 0.87 (95% CI 0.70-1.09) for body mass index (BMI, kg/m 2 ). Compared to a lowest lifelong BMI o20.7 kg/m 2 , the OR was 1.56 (95% CI 1.25-1.95) for a lowest lifelong BMI Z23.7 kg/m 2 . The OR was 0.74 (95% CI 0.60-0.93) for a lifelong increase of BMI Z6.1 kg/m 2 , compared to o1.6 kg/m 2 . No association emerged for history of diabetes, hypertension and hyperlipidemia. CONCLUSIONS: Overweight was modestly, inversely related to BPH. The hypothesis of reduced testosterone levels in obese individuals may explain the different BPH risk and need to be tested.

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Section: Discussionmentioning

confidence: 99%

History of weight and obesity through life and risk of benign prostatic hyperplasia

et al. 2005

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“…so that the prevalence of PIN in men enrolled in the national trial may be lower than in our study. The differential effects of T and DHT on the prostate are well described; several studies have demonstrated the primary dependence of the prostate and male extemal genital organ development on DHT (Imperato-McGinley et al, 1974;Walsh et al, 1974). whereas Wolffian duct derivatives (ejaculatory ducts, vas deferens.…”

Section: Discussionmentioning

confidence: 99%

The effect of finasteride on the prostate gland in men with elevated serum prostate-specific antigen levels

Côté

Skinner²,

Salem³

et al. 1998

Br J Cancer

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Summary Prostate cancer is a disease associated with androgens. It has been hypothesized that reducing the conversion of testosterone (T) to dihydrotestosterone (DHT) in the prostate by the use of the drug finasteride. a 5a-reductase inhibitor, will reduce the incidence of prostate cancer. We investigated the chemopreventive potential of finasteride by evaluating its effect on the prostate gland of men with elevated serum prostate-specific antigen (PSA). Fifty-two men with elevated PSA and prostate sextant biopsies negative for cancer were randomized to receive finastende 5 mg day-, (27 patients) or no medication (25 patients) for 12 months and were rebiopsied at 12 months.The biopsies were evaluated for the presence of cancer, the proportion of glandular and hyperplastic tissue, and the presence of high-grade prostatic intraepithelial neoplasia (PIN). Epithelial proliferation was assessed in the prestudy and 12-month biopsies by immunohistochemistry using antibody to proliferating cell nuclear antigen (PCNA). Serum blood samples were drawn at baseline and after 1. 3, 6 and 12 months of study. In the control group, serum levels of PSA and T were unchanged throughout the 12 months. In the finastende group, PSA decreased 48°o (P < 0.001), DHT decreased 670o (P < 0.001) and T increased 21 0°(P < 0.001). Histological evaluation of prestudy and 12-month biopsy specimens revealed that the finasteride group had a 300% reduction in the percentage of hyperplastic epithelial tissue (P = 0.002). although this decrease was not statistically significantly different between the finasteride and control groups (P = 0.11). In patients with PIN on prestudy biopsy, no change occurred in the PIN lesions with finasterde treatment. Finasteride also had no effect on the proliferation index of prostatic epithelial cells. Of the 27 patients treated with finastende, eight (309O) had adenocarcinoma of the prostate detected on the 12-month biopsy. compared with one (40o) of the control patients (P = 0.025). In the treatment group, six cancers occurred in the eight patients with PIN on the prestudy biopsy: in the observation group no cancers were detected in the five patients with PIN on the prestudy biopsy (P= 0.021). Two cancers occurred in the 19 men in the treatment group with no evidence of PIN on the prestudy biopsy. compared with one cancer in the 20 men in the observation group with no evidence of PIN on the prestudy biopsy (P = 0.60). This study, using a novel model for evaluating short-term efficacy of chemopreventive or therapeutic agents in men at high nsk of prostate cancer. provides little evidence that finasteride is an effective chemopreventive agent for prostate cancer in men with elevated PSA. Keywords: finastende: prostate carcinoma: intraepithelial neoplasia: proliferation Carcinoma of the prostate is the most frequentl diagnosed cancer in the US. Although the most important risk factor for prostate cancer is age (Ross et al. 1979). there is also profound -ariation in incidence between different racial groups in the US....

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“…Testosterone within the prostate is converted by the enzyme 5α-reductase to the more potent 5α-dihydrotestosterone (DHT). In conditions such as 5α-reductase deficiency, in which DHT is not biosynthesized, or androgen-insensitivity syndrome, a condition where AR mutations prevent ligand binding, the prostate fails to develop (10,11). Located on chromosome Xq11-12 (12), AR encodes a ligand-induced transcription factor that belongs to the steroid hormone gene family.…”

Section: The Prostate Gland and The Androgen Receptormentioning

confidence: 99%

Pathogenetic Influences of Human Herpesvirus 8 (HHV-8) in Prostate Cancer Progression

Mygatt¹

2012

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The mechanisms that give rise to androgen-independent prostate cancer (AIPC) are incompletely understood, resulting in a lack of treatment options for this fatal form of the disease. It is believed that most cases of AIPC are the result of constitutive activation of the androgen receptor (AR) pathway, leading us to hypothesize that chronic, prostatic infection could promote cancer progression as a result of pathogen virulence factors activating cell signaling pathways known to induce AR signaling. We found that human

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Steroid 5α-Reductase Deficiency in Man: An Inherited Form of Male Pseudohermaphroditism

Cited by 1,194 publications

References 9 publications

History of weight and obesity through life and risk of benign prostatic hyperplasia

History of weight and obesity through life and risk of benign prostatic hyperplasia

The effect of finasteride on the prostate gland in men with elevated serum prostate-specific antigen levels

Pathogenetic Influences of Human Herpesvirus 8 (HHV-8) in Prostate Cancer Progression

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