Positive association of the hepatic lipase gene polymorphism c.514C > T with estrogen replacement therapy response.

BACKGROUND: Hepatic lipase (HL), an enzyme present in the hepatic sinusoids, is responsible for the lipolysis of lipoproteins. Human HL contains four polymorphic sites: G-250A, T-710C, A-763G, and C-514T single-nucleotide polymorphism (SNPs). The last polymorphism is the focus of the current study. The genotypes associated with the C-514T polymorphism are CC (normal homozygous - W), CT (heterozygous - H), and TT (minor-allele homozygous - M). HL activity is significantly impaired in individuals of the TT and CT genotypes. A total of 58 post-menopausal women were studied. The subjects were hysterectomized women receiving hormone replacement therapy consisting of 0.625 mg of conjugated equine estrogen once a day. The inclusion criteria were menopause of up to three years and normal blood tests, radiographs, cervical-vaginal cytology, and densitometry. DNA was extracted from the buccal and blood cells of all 58 patients using a commercially available kit (GFX® - Amersham-Pharmacia, USA). RESULTS: Statistically significant reductions in triglycerides (t = 2.16; n = 58; p = 0.03) but not in total cholesterol (t = 0.14; n = 58; p = 0.89) were found after treatment. This group of good responders were carriers of the T allele; the CT and TT genotypes were present significantly more frequently than in the group of non-responders (p = 0.02 or p = 0.07, respectively). However, no significant difference in HDL-C (t = 0.94; n = 58; p = 0.35) or LDL-C (t = -0.83; n = 58; p = 0.41) was found in these patients. CONCLUSIONS: The variation in lipid profile associated with the C-514T polymorphism is significant, and the T allele is associated with the best response to ERT.

Genetic polymorphisms of cytochrome P450cl7alpha (CYP17) and progesterone receptor genes (PROGINS) in the assessment of endometriosis risk.

We designed the present study in order to evaluate the eventual role of polymorphisms in the genes encoding cytochrome P450c17alpha (CYP17) and the progesterone receptor (PROGINS) as risk factors for endometriosis development. Eligible cases consisted of 121 women with surgically confirmed endometriosis who underwent treatment in a hospital in São Paulo, Brazil during the period from September 2003 to September 2005. The 281 controls were participants with normal gynecological as well as pelvic ultrasound evaluation, who did not have any gynecological conditions during their reproductive lives such as pelvic pain and/or dyspareunia nor infertility history. Genomic DNA was obtained from buccal cells and processed for DNA extraction using the GFX DNA extraction kit (GE Healthcare). The CYP17 (-34T-->C) polymerase chain reaction-restriction fragment length polymorphism assay has been described previously, as has the progesterone receptor polymorphism (PROGINS) detection assay. PROGINS heterozygosis genotype frequencies were shown to be statistically higher in endometriosis cases compared with controls. On the other hand, differences in the CYP17 polymorphism (-34T-->C) frequencies were not even close to significance (p = 0.278) according to our findings.

Terapêutica estro-androgênica no climatério / Estrogen-androgen therapy in the climacterium

O estado de hipoestrogenismo após a menopausa pode levar à diminuição da lubrificação, elasticidade e do número de contrações rítmicas da vagina, dificultando a tolerância à penetração peniana mais profunda e continuada. Além disto, pode haver diminuição da libido e anorgasmia. Os androgênios atenuariam nestas alterações relacionadas com a sexualidade. Em geral, os efeitos virilizantes da metiltestosterona (hiscutismo, acne, mudança da voz e alopécia) são dose-e duração-dependentes do tratamento. Assim, recomenda-se associação de androgênios em doses baixas aos estrogênios para amenizar os distúrbios da sexualidde realcionados à deficiência hormonal e ainda para melhorar a qualidade de vida de mulheres na pós-menopausa, em especial nas que não haviam tido melhora com a terapia de reposição estrogênica isolada ou associada aos progestagênios. Portanto, a terapia estro-androgênica, quando bem indicada, pode constituir alternativa para as mulheres na pós-menopausa