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PubMed1998

Indole and benzimidazole derivatives as steroid 5alpha-reductase inhibitors in the rat prostate.

A novel series of indole and benzimidazole derivatives were synthesized and evaluated for their inhibitory activity of rat prostatic 5alpha-reductase. Among these compounds, 4-¿2-[1-(4,4'-dipropylbenzhydryl)indole-5-carboxamido]phenoxy¿buty ric acid (15) and its benzimidazole analogue 25 showed potent inhibitory activities for rat prostatic 5alpha-reductase (IC50 values of 9.6+/-1.0 and 13+/-1.5 nM, respectively), with the potency very close to that of finasteride. Compound 30, in which the moiety between the benzene ring and amide bond was replaced by quinolin-4-one ring, showed almost equipotent activity (IC50= 19+/-6.2nM) with the correspondent amide derivative 13. This result was consistent with the previous observation that the coplanarity of this moiety might contribute to the potent inhibitory activity.

5-alpha Reductase Inhibitors↗
PubMed2002

Oral contraceptives as anti-androgenic treatment of acne.

Although acne is seldom associated with high serum levels of androgens, it has been shown that female acne patients have definite increases in ovarian and adrenal androgen levels when compared to appropriate controls. As shown in several pilot and in multiple open and comparative studies, oral contraceptives (OCs) are effective in causing a significant regression of mild to moderate acne. These results have been confirmed by multicentre randomized trials where low-dose OCs did not cause side effects different from those of the placebo-controlled group. The beneficial effect of OCs is related to a decrease in ovarian and adrenal androgen precursors; to an increase in sex hormone-binding globulin (SHBG), which limits free testosterone; and to a decrease in 3a-androstenediol glucuronide conjugate, the catabolite of dihydrotestosterone (DHT) formed in peripheral tissues. The estrogen-progestin combination containing cyproterone acetate (CPA) is particularly effective in treating acne, since this progestin also has a direct peripheral anti-androgenic action in blocking the androgen receptor. Only two open studies and one randomized study on small numbers of patients have reported some efficacy of spironolactone used alone or in combination with an OC in the treatment of acne. The new non-steroidal anti-androgens flutamide and finasteride are being evaluated for the treatment of hirsutism. Oral antibiotics are prescribed to patients with inflammatory lesions, where they are effective in decreasing the activity of microbes, the activity of microbial enzymes, and leukocyte chemotaxis. Concomitant intake of an OC and an antibiotic usually prescribed for acne does not impair the contraceptive efficacy of the OC. A second effective contraceptive method should be used whenever there would be decreased absorption or efficacy of the OC (digestive problems, breakthrough bleeding), lack of compliance and use of a type or dose of antibiotic different from that usually prescribed for acne.Overall, the various approaches for the treatment of acne depend on the needs of the patient and on the therapeutic objectives. Low-dose OCs are effective in improving acne and have side effects similar to placebo. They can be used alone or in combination with other anti-acne agents. The physician prescribing an OC as an anti-androgen intervention should take into account the multiple factors involved in acne and be familiar with current non-hormonal agents for treating mild to moderate acne. Individuals presenting with moderate to severe acne, or not responding to an estrogen-progestin combination, should be referred to a dermatologist.

Acne Vulgaris↗
PubMed2000

Phytotherapy for benign prostatic hyperplasia.

OBJECTIVE: To systematically review the existing evidence regarding the efficacy and safety of phytotherapeutic compounds used to treat men with symptomatic benign prostatic hyperplasia (BPH). DESIGN: Randomized trials were identified searching MEDLINE (1966--1997), EMBASE, Phytodok, the Cochrane Library, bibliographies of identified trials and review articles, and contact with relevant authors and drug companies. The studies were included if men had symptomatic benign prostatic hyperplasia, the intervention was a phytotherapeutic preparation alone or combined, a control group received placebo or other pharmacologic therapies for BPH, and the treatment duration was at least 30 days. Key data were extracted independently by two investigators. RESULTS: A total of 44 studies of six phytotherapeutic agents (Serenoa repens, Hypoxis rooperi, Secale cereale, Pygeum africanum, Urtica dioica, Curcubita pepo) met inclusion criteria and were reviewed. Many studies did not report results in a method allowing meta-analysis. Serenoa repens, extracted from the saw palmetto, is the most widely used phytotherapeutic agent for BPH. A total of 18 trials involving 2939 men were reviewed. Compared with men receiving placebo, men taking Serenoa repens reported greater improvement of urinary tract symptoms and flow measures. Serenoa repens decreased nocturia (weighted mean difference (WMD) = -0.76 times per evening; 95% CI = -1.22 to -0.32; n = 10 studies) and improved peak urine flow (WMD = 1.93 ml s(-1); 95% CI = 0.72 to 3.14, n = 8 studies). Men treated with Serenoa repens rated greater improvement of their urinary tract symptoms versus men taking placebo (risk ratio of improvement = 1.72; 95% CI = 1.21 to 2.44, n = 8 studies). Improvement in symptoms of BPH was comparable to men receiving the finasteride. Hypoxis rooperi (n = 4 studies, 519 men) was also demonstrated to be effective in improving symptom scores and flow measures compared with placebo. For the two studies reporting the International Prostate Symptom Score, the WMD was -4.9 IPSS points (95% CI = -6.3 to -3.5, n = 2 studies) and the WMD for peak urine flow was 3.91 ml s(-1) (95% CI = 0.91 to 6.90, n = 4 studies). Secale cereale (n = 4 studies, 444 men) was found to modestly improve overall urological symptoms. Pygeum africanum (n = 17 studies, 900 men) may be a useful treatment option for BPH. However, review of the literature has found inadequate reporting of outcomes which currently limit the ability to estimate its safety and efficacy. The studies involving Urtica dioica and Curcubita pepo are limited although these agents may be effective combined with other plant extracts such as Serenoa and Pygeum. Adverse events due to phytotherapies were reported to be generally mild and infrequent. CONCLUSIONS: Randomized studies of Serenoa repens, alone or in combination with other plant extracts, have provided the strongest evidence for efficacy and tolerability in treatment of BPH in comparison with other phytotherapies. Serenoa repens appears to be a useful option for improving lower urinary tract symptoms and flow measures. Hypoxis rooperi and Secale cereale also appear to improve BPH symptoms although the evidence is less strong for these products. Pygeum africanum has been studied extensively but inadequate reporting of outcomes limits the ability to conclusively recommend it. There is no convincing evidence supporting the use of Urtica dioica or Curcubita pepo alone for treatment of BPH. Overall, phytotherapies are less costly, well tolerated and adverse events are generally mild and infrequent. Future randomized controlled trials using standardized preparations of phytotherapeutic agents with longer study durations are needed to determine their long-term effectiveness in the treatment of BPH.

Humans↗
PubMed1995

Structure-activity relationships for inhibition of type 1 and 2 human 5 alpha-reductase and human adrenal 3 beta-hydroxy-delta 5-steroid dehydrogenase/3-keto-delta 5-steroid isomerase by 6-azaandrost-4-en-3-ones: optimization of the C17 substituent.

A variety of C17 amide-substituted 6-azaandrost-4-en-3-ones were prepared and tested versus human type 1 and 2 steroid 5 alpha-reductase (5AR) and human adrenal 3 beta-hydroxy-delta 5-steroid dehydrogenase/3-keto-delta 5-steroid isomerase (3BHSD) in order to optimize potency versus both isozymes of 5AR and selectivity versus 3BHSD. Two series of potent and selective C17 amides were discovered, 2,5-disubstituted anilides and (arylcycloalkyl)amides. Compounds from each series with picomolar IC50's versus human type 2 5AR and low nanomolar to picomolar IC50's versus human type 1 5AR possessing 100-500-fold selectivity versus 3BHSD were identified. A conformational model to predict 3BHSD potency was developed which could rationalize 3BHSD potency within three different series of compounds. Evaluation of some optimal compounds from this series in a chronic castrated rat model of 5AR inhibitor induced prostate involution, and pharmacokinetic measurements identified compounds (9, 12, 16, and 29) with good in vivo efficacy and half-life in the dog. An intact rat model of in vivo selectivity for 5AR versus 3BHSD inhibition was also developed. Dual inhibitors of both human 5AR's may show advantages over type 2 selective 5AR inhibitors, such as finasteride (1), in the treatment of disease states which depend upon dihydrotestosterone.

3-Hydroxysteroid Dehydrogenases↗
PubMed2000

Benzo[c]quinolizin-3-ones: a novel class of potent and selective nonsteroidal inhibitors of human steroid 5alpha-reductase 1.

The synthesis and biological evaluation of a series of novel, selective inhibitors of isoenzyme 1 of human 5alpha-reductase (5alphaR) (EC 1.3.99.5) are reported. The inhibitors are 4aH- (19-29) or 1H-tetrahydrobenzo[c]quinolizin-3-ones (35-47) bearing at positions 1, 4, 5, and 6 a methyl group and at position 8 a hydrogen, methyl group, or chlorine atom. All these compounds were tested toward 5alphaR-1 and 5alphaR-2 expressed in CHO cells (CHO 1827 and CHO 1829, respectively) resulting in selective inhibitors of the type 1 isoenzyme, with inhibitory potencies (IC(50)) ranging from 7.6 to 9100 nM. The inhibitors of the 4aH-series, having a double bond at position 1,2, were generally less active than the corresponding inhibitors of the 1H-series having the double bond at position 4,4a on the A ring. The presence of a methyl group at position 4 (as in compounds 39-40 and 45-47), associated with a substituent at position 8, determined the highest inhibition potency (IC(50) from 7.6 to 20 nM). Compounds 39 and 40, having K(i) values of 5.8+/-1.8 and 2.7+/-0.6 nM, respectively, toward 5alphaR-1 expressed in CHO cells, were also tested toward native 5alphaR-1 in human scalp and 5alphaR-2 in human prostate homogenates, in comparison with finasteride and the known 5alphaR-1-selective inhibitor LY191704, and their mechanism of inhibition was determined. They both inhibited the enzyme through a reversible competitive mechanism and again were selective inhibitors of 5alphaR-1 with IC(50) values of 41 nM. These specific features make these inhibitors suitable candidates for further development as drugs in the treatment of DHT-dependent disorders such as acne and androgenic alopecia in men and hirsutism in women.

5-alpha Reductase Inhibitors↗
PubMed2002

Synthesis and evaluation of 2'-substituted 4-(4'-carboxy- or 4'-carboxymethylbenzylidene)-N-acylpiperidines: highly potent and in vivo active steroid 5alpha-reductase type 2 inhibitors.

Sixteen compounds derived from N-acyl-4-benzylidenepiperidine-4'-carboxylic acids were synthesized and evaluated for inhibition of rat and human steroid 5alpha-reductase isozymes types 1 and 2. In the dicyclohexylacetyl series, fluorination in the 2-position of the benzene nucleus (15), exchange of the carboxy group by a carboxymethyl moiety (20), and combination of both structural modifications (25) led to highly active inhibitors of the human type 2 isozyme (IC(50) values: 15, 11 nM; 20, 6 nM; 25, 7 nM; finasteride, 5 nM). In vivo all compounds tested markedly reduced the prostate weights in castrated testosterone-treated rats. Oral activity was shown for compound 7. From the finding that compound 15 is active in the rat, although it is a rather poor inhibitor of the rat enzyme and is a strong inhibitor of the human enzyme, it is concluded that it should be highly potent in men.

5-alpha Reductase Inhibitors↗
PubMed2006

Novel 5alpha-reductase inhibitors: synthesis, structure-activity studies, and pharmacokinetic profile of phenoxybenzoylphenyl acetic acids.

Novel substituted benzoyl benzoic acids and phenylacetic acids 1-14 have been synthesized and evaluated for inhibition of rat and human steroid 5alpha-reductase isozymes 1 and 2. The compounds turned out to be potent and selective human type 2 enzyme inhibitors, exhibiting IC(50) values in the nanomolar range. The phenylacetic acid derivatives were more potent than the analogous benzoic acids. Bromination in the 4-position of the phenoxy moiety led to the strongest inhibitor in this class (12; IC(50) = 5 nM), which was equipotent to finasteride. Since oral absorption is essential for a potential drug, 12 was further examined. In the parallel artificial membrane permeation assay (PAMPA) it turned out to be a good permeator, whereas it was a medium permeator in Caco2 cells. After oral administration (40 mg/kg) to rats a high bioavailability and a biological half-life of 5.5 h were observed, making it a promising candidate for clinical evaluation.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2001

Molecular epidemiologic studies within the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

OBJECTIVE: To conduct timely epidemiologic investigations of molecular/genetic markers that may contribute to the development of prostate, lung, colorectal, or other cancers within the Selenium and Vitamin E Cancer Prevention Trial (SELECT), and to evaluate interactions between these markers and the study interventions. METHODS: The epidemiologic studies within SELECT will be based on 32,400 men aged 55 years or older (age 50 or older for the African-American men) enrolled into an intergroup, randomized, placebo-controlled, double-blind, phase III prevention trial of supplemental selenium and vitamin E developed and funded by the National Cancer Institute, and coordinated by the Southwest Oncology Group. During the 12-year study period approximately 1500-2000 cases of prostate cancer, 800 lung cancers, and 500 colon cancers are estimated to be diagnosed, based on data from the ongoing Prostate Cancer Prevention Trial of finasteride. A modified fasting blood sample will be processed to collect plasma for analysis of micronutrients, hormones, cytokines, and other proteins. Buffy-coat derived white blood cells collected at baseline will be used for isolation of DNA and establishment of immortalized cell lines. Red blood cells will be stored for analysis of hemoglobin adducts and other components. RESULTS: Specific results anticipated from these molecular studies will provide information on factors hypothesized to contribute to prostate cancer risk and that may modify the efficacy of either trial supplement, including: steroid sex hormones and several polymorphic genes that encode proteins affecting androgenic stimulation of the prostate, including the androgen receptor, steroid 5alpha-reductase type II, CYP17, and beta-hydroxysteroid dehydrogenase; polymorphisms of DNA repair genes and carcinogen metabolism genes, including those involved in the activation of chemical carcinogens to reactive intermediates (e.g., CYP1A1) or the detoxification of reactive intermediates (e.g., glutathione S-transferase M1); DNA and protein adducts; and insulin-like growth factors and leptin. CONCLUSION: SELECT offers an excellent opportunity to conduct molecular epidemiologic investigations to assess gene-environment interactions and their role in prostate, lung, and colon carcinogenesis.

Colorectal Neoplasms↗
PubMed2002

Chemoprevention of prostate cancer.

Chemoprevention is prevention of cancer by administering natural or synthetic chemicals. Anti-androgens are among the promising chemopreventive agents for prostate cancer because prostate epithelium is androgen dependent. A National Cancer Institute supported large, randomized, clinical prostate cancer chemoprevention trial has been conducted to test the efficacy of finasteride, an inhibitor of 5-a-reductase, which converts testosterone to 5-hydroxy-testosterone. Now the focus is on micronutrients and phytochemicals, which have potential preventive effects against prostate cancer. Lycopene, soy isoflavones, vitamin E and selenium are among the most promising nutritional chemopreventive agents. Another NCI supported large clinical chemoprevention trial was recently started to investigate the efficacy of selenium and vitamin E, alone or in combination in the prevention of prostate cancer. Inclusion of appropriate biomarkers in clinical trials will help elucidate the mechanisms by which genetic and epigenetic pathways of carcinogenesis are modulated by nutrients and phytochemicals.

Animals↗
PubMed1999

[Androgenetic alopecia, hirsutism and hypertrichosis].

Having too much hair on the face or the body and not enough on the scalp respectively, is generally not a mirror of a life-threatening disease. However, the emotional impact of such cosmetic problems may be remarkable in the individual case. Currently rational treatment options are becoming increasingly available to correct such hair problems. This review highlights the new therapeutic achievements in the treatment of both androgenetic alopecia and hirsutism. Oral treatment of male patterned hair loss with finasteride in men is emphasized, and the use of antiandrogens in women is discussed. In addition, the mode of action and clinical results of topical minoxidil treatment find mention. The second part of the review deals with hirsutism and hypertrichosis. The diagnostic steps and investigations are briefly reviewed, and the advances in laser treatment of hirsutism and hypertrichosis are presented.

Adult↗
PubMed2006

Drug Insight: 5alpha-reductase inhibitors for the treatment of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common problem among older men, which is characterized by an enlarged prostate, lower urinary tract symptoms, and decreased flow of urine. It is a progressive disease that can lead to complications such as acute urinary retention (AUR) or a need for BPH-related surgery in some men. Dihydrotestosterone is the primary androgen involved in both normal and abnormal prostate growth and 5alpha-reductase inhibitors (5ARIs) inhibit the conversion of testosterone to dihydrotestosterone. There are two 5ARIs licensed for the treatment of BPH; dutasteride, which inhibits both type 1 and type 2 isoenzymes of 5alpha reductase, and finasteride, which inhibits the type 2 isoenzyme. Both 5ARIs have been shown to decrease prostate volume, improve urinary flow and lower urinary tract symptoms and reduce the risk of AUR and BPH-related surgery. The prevention of disease progression, by treating the underlying cause, and the alleviation of symptoms are important aims of BPH therapy. 5ARIs are the only currently available medical therapy that can reduce the risk of AUR and BPH-related surgery while providing long-term symptom control. This provides a mandate for their use in men with enlarged prostates (volume >or=30 ml), who are at increased risk of disease progression.

5-alpha Reductase Inhibitors↗
PubMed1999

Effects of new 17alpha-hydroxylase/C(17,20)-lyase inhibitors on LNCaP prostate cancer cell growth in vitro and in vivo.

Our laboratory has been developing new inhibitors of a key regulatory enzyme of testicular and adrenal androgen synthesis 17alpha-hydroxylase/C(17,20)-lyase (P450c17), with the aim of improving prostate cancer treatment. We designed and evaluated two groups of azolyl steroids: delta5-non-competitive inhibitors (delta5NCIs), VN/63-1, VN/85-1, VN/87-1 and their corresponding delta4 derivatives (delta4NCIs), VN/107-1, VN/108-1 and VN/109-1. The human P450c17 gene was transfected into LNCaP human prostate cancer cells, and the resultant LNCaP-CYP17 cells were utilized to evaluate the inhibitory potency of the new azolyl steroids. VN/85-1 and VN/108-1 had the lowest IC50 values of 1.25 +/- 0.44 nM and 2.96 +/- 0.78 nM respectively, which are much lower than that of the known P450 inhibitor ketoconazole (80.7 +/- 1.8 nM). To determine whether the compounds had direct actions on proliferation of wild-type LNCaP cells, cell growth studies were performed. All of the delta5NCIs and VN/108-1 blocked the growth-stimulating effects of androgens. In steroid-free media, the delta5NCIs decreased the proliferation of LNCaP cells by 35-40%, while all of the delta4NCIs stimulated LNCaP cells growth 1.5- to 2-fold. In androgen receptor (AR) binding studies, carried out to determine the mechanism of this effect, all of the delta4NCIs (5 microM) displaced 77-82% of synthetic androgen R1881 (5 nM) from the LNCaP AR. The anti-androgen flutamide and the delta5NCIs displaced 53% and 32-51% of R1881 bound to AR respectively. These results suggested that the delta5NCIs may also be acting as anti-androgens. We further evaluated our inhibitors in male severe combined immunodeficient mice bearing LNCaP tumour xenografts. In this model VN/85-1 was as effective as finasteride at inhibiting tumor growth (26% and 28% inhibition, respectively) and the inhibitory effect of VN/87-1 was similar to that of castration (33% and 36% inhibition respectively). These results suggest that VN/85-1 and VN/87-1 may be potential candidates for treatment of prostate cancer.

Animals↗
PubMed2003

Medical therapy for benign prostatic hyperplasia: sexual dysfunction and impact on quality of life.

Therapies for benign prostatic hyperplasia (BPH) may either improve or exacerbate sexual function with an ensuing impact on quality of life. Here we review a total of 73 papers on medical therapies for BPH with a focus on the effects of different pharmacological agents on sexual function. For example, certain alpha(1)-adrenergic receptor blockers may improve erectile function; however, ejaculatory dysfunction with one of these agents, tamsulosin, occurs at a rate of 4-18%, rising to 30% with long-term use. In addition, treatment with the 5 alpha-reductase inhibitor finasteride is associated with problems of ejaculation (2.1-7.7%), erection (4.9-15.8%), and libido (3.1-5.4%). Such significant and undesirable complications in relation to sexual function produce a well-documented negative impact on quality of life. Thus, optimal treatment for men with BPH requires the use of agents that demonstrate efficacy and safety with fewer sexual side effects.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2004

Identification and characterization of somatic steroid 5alpha-reductase (SRD5A2) mutations in human prostate cancer tissue.

Prostate cancer is a very common disease in industrialized countries and it is known to be androgen-dependent. The human SRD5A2 gene encodes the prostatic (or type II) steroid 5alpha-reductase, which catalyses the irreversible conversion of testosterone to dihydrotestosterone (DHT), the most active androgen in the prostate. We have sequenced the entire protein-coding region of this locus in 30 microdissected prostate adenocarcinomas. We identified a total of 17 de novo amino-acid substitutions in 13 of these tumors. We also identified six additional silent substitutions. In total, 18 out of 30 (60%) of the tumors examined had de novo somatic substitutions in the prostatic steroid 5alpha-reductase-coding region. We also characterized all of the SRD5A2 missense substitutions biochemically and pharmacologically, using three 5alpha-reductase inhibitors, including finasteride. The biochemical parameters of the distinct 5alpha-reductase missense substitutions varied substantially. We note that two out of the three recurrent SRD5A2 missense substitutions increased 5alpha-reductase in vitro activity, while the third one is essentially neutral. These findings are consistent with a role for increased DHT levels in the prostate through increased activity of the SRD5A2 locus in prostate cancer progression, in a subset of patients. Our pharmacologic studies also reveal substantial variability for each 5alpha-reductase inhibitor. These data, therefore, should be taken into account in both prevention as well as therapeutic trials of prostate cancer utilizing 5alpha-reductase inhibitors.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1999

Medical therapy for BPH: expanding our treatment paradigm?

Medical therapy for relief of symptoms of benign prostatic hyperplasia (BPH) is now a clinical reality. The challenge for urologists treating BPH with medical therapy is how to rationally employ the two proven classes of medications,the alpha blockers and finasteride, in their practice. To accomplish this, we must critically examine the results of multiple important clinical BPH trials published over the last decade and examine the short and long term effect of the various available medical therapies on symptoms, objective progression and consequences of the disease process and whether evidence based indicators will allow us to choose appropriate therapies. It appears that we can rationalize our medical therapy decisions, taking into consideration severity of disease, prostate size (and perhaps PSA) and most importantly, the patients' longterm expectations for treatment outcome. But first physicians must decide for themselves whether to expand their treatment paradigm beyond short term symptom relief to encompass long term durability and even prevention of the consequences of the long term progression of BPH.

Journal Article↗
PubMed2001

Treatment of lower urinary tract symptoms suggestive of benign prostatic obstruction in real life practice in France.

The objective of this work is to describe the profile of prevalent and incident populations suffering from lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO) and to analyse the management of care by 620 general practitioners (GPs) in France in 1997 and 1998. Patient records were extracted from the THALES database. Special attention was given to the use of medical therapy and switch rates (ie change to another or combination with another drug). In real life practice (RLP) French GPs predominantly utilise alpha(1)-adrenoceptor antagonists for the treatment of LUTS. This is in agreement with available evidence from randomised controlled trials (RCTs) with different medical therapies (alpha(1)-adrenoceptor antagonists, finasteride, plant extracts). On the contrary, the relatively high usage of phytotherapy might be explained by traditional and personal preferences. Using purely descriptive statistics, newer alpha(1)-adrenoceptor antagonists, alfuzosin and tamsulosin, seem to be the most frequently prescribed medical therapy for new patients and are, moreover, associated with a low switch rate.Prostate Cancer and Prostatic Diseases (2001) 4, 124-131

Journal Article↗
PubMed2001

Impact of treatment of BPH on sexuality.

Benign prostatic hyperplasia (BPH) can have a profound affect on a patient's quality of life and sexual function and is considered by patients to be one of the most important aspects affected by the disease. Different treatments can produce a variable response in terms of the patient's quality of life, including sexual activity and satisfaction. Varying rates of erectile dysfunction (ED) and retrograde ejaculation following surgery for BPH have been reported. In general, the incidence of these side-effects is less after minimally invasive therapies, such as interstitial laser coagulation and transurethral microwave therapy, but the data available are limited. The lowest rates of sexual dysfunction are reported with medical therapies. The 5alpha-reductase inhibitor, finasteride, can result in ED in 5-9% of patients and ejaculation disorders in 0.8-2.0%. With the exception of tamsulosin, alpha(1) blockers are associated with a low rate of sexual dysfunction. No cases of ED have been reported with alfuzosin and abnormal ejaculation with terazosin or alfuzosin is negligible. Indeed, early research suggests a beneficial effect of alpha(1) blockers on sexual function. In addition to information on the efficacy of a particular therapy, patients should be informed of side effects, in particular those relating to sexual function, in order that they can make informed treatment decisions.Prostate Cancer and Prostatic Diseases (2001) 4, S12-S16

Journal Article↗
PubMed2000

Development of a health-related quality of life questionnaire for women with androgenetic alopecia.

Despite the negative effects of androgenetic alopecia (AGA), no standardized health-related quality of life (HRQOL) questionnaire which is both specific to women and suitable for use in clinical trials currently exists. A questionnaire to assess HRQOL in women with AGA, the Women's Androgenetic Alopecia Quality of Life Questionnaire (WAA-QOL), was recently developed. Aspects of life affected by AGA were generated from literature review, discussion with experts, and a focus group. The number of issues identified was reduced based on importance and relevance to women with AGA. A questionnaire was then constructed and pilot-tested for comprehension. The resulting 25-item instrument was later included in a double-blind, placebo-controlled clinical trial of finasteride 1 mg for the treatment of hair thinning in postmenopausal women (n = 137). Based on test characteristics, several questions were eliminated, resulting in a 16-item questionnaire. The WAA-QOL exhibited excellent test-retest reliability overall (intraclass correlation coefficient = 0.89), and for individual items (kappa = 0.66-0.85), as well as high internal consistency (Crohnbach's alpha = 0.98). Responsiveness of the questionnaire could not be assessed. The WAA-QOL is self-completed in about 10 min, exhibits good content validity, internal consistency, and test-retest reliability, and may be useful in assessing the impact of female AGA on HRQOL or in evaluating therapeutic effects in clinical trials.

Adult↗