dutasteride and Breast-Neoplasms

Treatment for frontal fibrosing alopecia (FFA) is challenging, and its treatment regimen often mirrors other lymphocytic-predominant cicatricial alopecia. 5-alpha-reductase inhibitor (5ARI) has been reported with some treatment success in severe cases of FFA.. To carry out evidence-based analysis of articles published on treatment efficacy and safety of 5-alpha-reductase inhibitor for the treatment of FFA.. Articles published on the use of 5ARI to treat FFA between 2005 and 2017 were reviewed, analysed and graded according to the American College of Physicians outcome study grading system.. There were two studies with moderate level of evidence that described the efficacy of 5ARI for the treatment of FFA. 5ARI was commonly used as adjunctive therapy with positive results in recalcitrant disease. Mild to moderate hair regrowth was reported in one grade 2 and three lower grade (one grade 3 and two grade 4) studies. There is limited evidence on the safety aspects of this medication in most studies that were analysed.. Database studies might not fully account for confounders and are subjected to variations in methodology and data collection.. This review demonstrated that FFA patients treated with 5ARI could achieve either disease stability or reduction in the rate of progression in selected cases. A well-designed randomized, double-blind, controlled study would strengthen the role of 5ARI as part of treatment armamentarium for FFA.

Topics: 5-alpha Reductase Inhibitors; Alopecia; Breast Neoplasms; Depression; Dutasteride; Evidence-Based Medicine; Female; Fibrosis; Finasteride; Forehead; Hair; Humans; Scalp; Sexual Dysfunction, Physiological

Prevention of cancer remains the most promising strategy for reducing both its incidence and the mortality due to this disease. For more than four decades, findings from epidemiology, basic research and clinical trials have informed the development of lifestyle and medical approaches to cancer prevention. These include selective oestrogen receptor modulators and aromatase inhibitors for breast cancer, the 5-α-reductase inhibitors finasteride and dutasteride for prostate cancer, and the development of vaccines for viruses that are associated with specific cancers. Future directions include genetic, proteomic and other molecular approaches for identifying pathways that are associated with cancer initiation and development, as well as refining the search for immunologically modifiable causes of cancer.

Topics: Aromatase Inhibitors; Azasteroids; Breast Neoplasms; Cancer Vaccines; Diet; Dutasteride; Female; Finasteride; Humans; Immunotherapy; Life Style; Male; Motor Activity; Neoplasms; Nicotiana; Obesity; Prostatic Neoplasms; Selective Estrogen Receptor Modulators; Vaccines

To what degree the associations between PCa risk and family history of prostate cancer (PCa) and/or breast cancer (BCa) are attributable to screening biases is unclear. We examined these questions within the REDUCE study, where biopsies were largely independent of prostate specific antigen (PSA) minimizing screening biases.. Data were from REDUCE, which tested dutasteride 0.5 mg daily for PCa risk reduction in men with PSA 2.5-10.0 ng mL(-1) and a negative prestudy biopsy. Among men undergoing at least one on-study biopsy with complete data (n = 6415; 78.1%), the association between family history and PCa risk was tested using multivariate logistic regression adjusting for clinicodemographic characteristics.. A family history of PCa alone was associated with increased PCa diagnosis (OR: 1.47, 95%CI: 1.22-1.77). In North America, PCa family history was not related to PCa diagnosis (OR: 1.02, 95%CI: 0.73-1.44), whereas outside North America, PCa family history was significantly related to diagnosis (OR: 1.72, 95%CI: 1.38-2.15) (P-interaction = 0.01). A family history of both PCa and BCa (OR: 2.54, 95%CI: 1.72-3.75) but not BCa alone (OR: 1.04, 95%CI: 0.84-1.29) was associated with increased PCa risk versus no family history and irrespective of geographical region.. In REDUCE, PCa family history was significantly related to PCa diagnosis, although only for men outside North America. The presence of both PCa and BCa family history significantly increased risk versus PCa family history alone, irrespective of geographical region. Ultimately, our observations may support the need for changes in how we address family history in terms of both risk of PCa diagnosis and general risk stratification.

Topics: 5-alpha Reductase Inhibitors; Aged; Anticarcinogenic Agents; Azasteroids; Breast Neoplasms; Cohort Studies; Double-Blind Method; Drug Administration Schedule; Dutasteride; Female; Humans; Incidence; Logistic Models; Male; Medical History Taking; Middle Aged; Multivariate Analysis; Odds Ratio; Prostatic Neoplasms; Risk Assessment; Risk Factors

Recent evidence indicates that progesterone metabolites play important roles in regulating breast cancer. Previous studies have shown that breast carcinoma and tumorigenic breast cell lines have higher 5alpha-reductase and lower 3alpha-hydroxysteroid oxidoreductase (3alpha-HSO) and 20alpha-HSO activities and mRNA expression levels than normal tissue and non-tumorigenic cell lines. The 5alpha-reduced progesterone metabolites such as 5alpha-dihydroprogesterone (5alphaP) promote both mitogenic and metastatic activity in breast cell lines in culture, whereas the 4-pregnene metabolites, 4-pregnen-3alpha-ol-20-one (3alphaHP) and 4-pregnen-20alpha-ol-3-one (20alphaHP) have the opposite (anti-cancer-like) effects. The 5alpha-reductase inhibitor dutasteride has been shown to inhibit 5alpha-reduction of testosterone to 5alpha-dihydrotestosterone in prostate tissue, resulting in decreased prostate volume. The aim of this study was to determine if dutasteride is an effective inhibitor of progesterone 5alpha-reduction in human breast cell lines and if such inhibition reduces mammary cell proliferation and detachment. The effect of dutasteride on progesterone metabolizing enzyme activities and mRNA expression were examined in tumorigenic MCF-7 and non-tumorigenic MCF-10A human breast cell lines. Dutasteride (10(-6)M) inhibited progesterone conversion to 5alpha-pregnanes by >95% and increased 4-pregnene production. The results indicated that effects of dutasteride on the progesterone metabolizing enzymes are due to direct inhibition of 5alpha-reductase activity and to altered levels of expression of 5alpha-reductase and HSO mRNAs. Treatment of cells with progesterone without medium change for 72 h resulted in significant conversion to 5alpha-pregnanes and increases in cell proliferation and detachment. The increases in proliferation and detachment were blocked by dutasteride and were reinstated by concomitant treatment with 5alphaP, providing proof-of-principle that the effects were due not to progesterone but to the 5alpha-reduced metabolites. This study provides the first evidence that dutasteride is a potent progesterone 5alpha-reductase inhibitor and that such inhibition may be beneficial in breast cancer.

Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; 5-alpha Reductase Inhibitors; Azasteroids; Breast; Breast Neoplasms; Cell Adhesion; Cell Line; Cell Proliferation; Dutasteride; Enzyme Inhibitors; Female; Humans; Molecular Structure; Oxidoreductases; Pregnanes; Pregnenes; Progesterone; RNA, Messenger