Effects of low- or high-dose hormone therapy on fasting and post-methionine homocysteine levels in postmenopausal women.

OBJECTIVE: To evaluate the effect of two different hormone therapy (HT) doses on fasting and post-methionine homocysteine levels, an independent risk factor for cardiovascular and thromboembolic diseases. METHODS: Forty-eight women in natural postmenopause randomly received calcium 1 mg/day (control group; n = 12) or calcium plus low dose (1 mg estradiol plus 0.5 mg norethisterone; n = 18) or high dose (2 mg estradiol plus 1 mg norethisterone; n = 18) HT in a 6-month randomized, controlled, prospective study. RESULTS: Folate levels did not vary in any group, while levels of vitamin B12 significantly decreased after low- (-12.2 +/- 6.6%; p < 0.04) or high-dose HT (-13.9 +/- 6.1%; p < 0.01). Fasting homocysteine was reduced by either HT dose in a way that was inversely related to pretreatment homocysteine levels (-0.675x; r = 0.644; p < 0.0001). Modification of post-load homocysteine increase was influenced by the HT dose and inversely related to the homocysteine response to methionine observed at baseline. The regression slope observed with the low-dose HT (-1.637x; r = 0.57; p < 0.02) was significantly steeper (p < 0.001) than that observed with the high-dose HT (-0.304x; r = 0.554; p < 0.03) dose. CONCLUSIONS: Low- or high-dose HT similarly influences fasting homocysteine levels. Low-dose HT seems to be more effective than high-dose HT in reducing the post-methionine homocysteine increase.

Early prenatal diagnosis of recurrent 46,XY partial gonadal dysgenesis.

OBJECTIVES: We present a case of early prenatal diagnosis of recurrent 46,XY partial gonadal dysgenesis, by combining early genetic and sonographic evaluations. METHODS: The conceptus of a mother with a first child affected by 46,XY gonadal dysgenesis was sonographically evaluated at 21- and 23-mm BPD (12(+2) and 12(+6) LMP-based age) and the female genitalia were observed. Karyotype analyses was performed on amniotic fluid and it revealed a 46,XY complement without mosaicism. SRY was amplified by PCR for molecular analyses. RESULTS: We observed a discordance between female phenotype detected at 21 and 23 mm of biparietal diameter (12(+2) and 12(+6) LMP-based age) and male karyotype. In the child and the fetus, seminiferous cords were not recognisable, whereas rare Leydig cells and no germ cells could be identified. Internal and external genitalia were sexually ambiguous in the child and feminized in the fetus. CONCLUSION: This is the first case of early prenatal diagnosis of recurrent 46,XY partial gonadal dysgenesis and it points to the importance of combining early analyses of genetic sex with sonography in the management of anomalies of sexual development, with particular regard to syndromes for which the risk of recurrence is little understood.

Continuous combined hormone replacement therapy with oral 17beta-estradiol and norethisterone acetate improves homocysteine metabolism in postmenopausal women.

OBJECTIVE: To evaluate the effect of a continuous combined oral hormone replacement therapy (HRT) on basal and post-methionine load homocysteine levels in postmenopausal women. DESIGN: Twenty-two postmenopausal women (PMW) were randomly allocated to receive either continuous combined oral HRT (2 mg of estradiol plus 1 mg of norethisterone acetate; n = 11) or no treatment (controls, n = 11) for 6 months. A methionine oral load (0.1 g/kg body weight) was performed in each subject at time 0 and after 6 months. Serum homocysteine levels were measured by high-performance liquid chromatography in samples collected at time 0 and at 4, 8, and 24 h after the methionine load, while levels of vitamin B6 (by high-performance liquid chromatography) and B12 and folate (both by ELISA) were assayed in samples collected at time 0. RESULTS: Serum levels of glucose and body mass index increased in treated PMW, whereas folate decreased in controls. In treated PMW, basal homocysteine tended to decrease (10.6 +/- 3.3 micromol/L vs. 9.62 +/- 2.8 micromol/L, p = 0.062), whereas in controls it significantly increased (10.7 +/- 2.65 micromol/L vs. 12.17 +/- 3.89 micromol/L, p < 0.05). This increase was not significant after correction for vitamin status (p = 0.072). Homocysteine values 4 h (31.9 +/- 13.53 micromol/L vs. 39.83 +/- 22.53 micromol/L, p < 0.05) and 8 h (35.1 +/- 13.13 vs. 43.34 +/- 22.15 micromol/L) after methionine, and integrated homocysteine response to methionine (392.5 +/- 133.8 micromol/24 h vs. 458.8 +/- 104.8 micromol/24 h; p < 0.05), were significantly reduced in HRT-treated, but not in untreated, PMW. CONCLUSIONS: Continuous combined oral HRT with17beta-estradiol plus norethisterone acetate reduces homocysteine levels, mainly after a methionine load. This effect seems to be independent of vitamin status and may have positive implications for the prevention of cardiovascular diseases in PMW.