Profile of Brazilian climacteric women: results from the Brazilian Menopause Study.

OBJECTIVE: This study aims to understand the epidemiological characteristics of Brazilian menopausal women, and their view on menopause hormone therapy (MHT). METHODS: A national cross-sectional study with 1500 women between 45 and 65 years old was carried out through questionnaires. RESULTS: The overall median age of participants was 52 [47-56] years, and 55 [52-59] years for the postmenopausal subgroup. Menstrual irregularity started at median age 46 [44-49] years. Median menopause age was 48 [45-51] years with no differences between socioeconomic classes. The prevalence of any climacteric symptoms was 87.9% and hot flashes started at median age 47 [45-50] years. Among women in menopause/menopausal transition, 52.1% received any medical prescription, and MHT was recommended for 22.3%. Among those who started MHT, 45.4% were still using the treatment and the median duration of use was 8 months, but different among socioeconomic classes (24 months for class A against 3 months for class D/E). CONCLUSIONS: In this first Brazilian national population-based study on menopause and MHT, it was observed that, in spite of being symptomatic when entering menopause around 48 years of age, only a small part of Brazilian women started MHT and the median duration of treatment was less than 1 year, but the duration was higher for higher socioeconomic class.

Effects of estradiol, progestogens, and of tibolone on breast proliferation and apoptosis.

AIM: To study the effects of estrogen therapy, alone or combined with progestogens, and of tibolone on the expression of proliferation and apoptosis markers in normal breast tissue. METHODS: Thirty 250-day-old Wistar rats were castrated and 3 weeks later received one of the following treatments by gavage for 5 weeks: (1) estradiol benzoate; (2) estradiol benzoate + medroxyprogesterone acetate; (3) estradiol benzoate + norethisterone acetate; (4) estradiol benzoate + dydrogesterone; (5) tibolone; (6) placebo. Following treatment, the expression of proliferating cell nuclear antigen (PCNA) and caspase-3 was analyzed by quantitative immunohistochemistry in the breast tissue, and proliferation and apoptosis were analyzed semiquantitatively by microscopic imaging. RESULTS: There was a statistically significant difference among the groups for PCNA, caspase-3 and the caspase-3 : PCNA ratio. Tibolone was associated with the lowest proliferative activity, followed by estradiol benzoate + dydrogesterone; however, estradiol benzoate + dydrogesterone showed the greatest rate of apoptosis. CONCLUSIONS: The various progestogens can have more or less proliferative and pro-apoptotic effects than estradiol alone. Among the treatment schemes analyzed, the estradiol + dydrogesterone combination resulted in a higher apoptosis rate in relation to the proliferation rate and tibolone was associated with the lowest proliferation.

Is expression of rat breast matrix components influenced by estrogen, progestins and tibolone?

AIM: To study the effects of estrogen therapy, alone or combined with progestogens, and of tibolone on the expression of heparanase (HSPE), extracellular matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9), perlecan and proliferating cell nuclear antigen (PCNA) in normal breast tissue. METHODS: Thirty 250-day-old Wistar rats were castrated and 3 weeks later received one of the following treatments by gavage for 5 weeks: (1) estradiol benzoate; (2) estradiol benzoate + medroxyprogesterone acetate; (3) estradiol benzoate + norethisterone acetate; (4) estradiol benzoate + dydrogesterone; (5) tibolone; (6) placebo. Following treatment, the expressions of mRNA for HSPE, MMP-2 and MMP-9 were analyzed by real-time PCR and the protein expressions of HSPE, MMP-2, MMP-9, perlecan and PCNA were quantified by immunohistochemistry. RESULTS: There was a statistically significant difference among the groups for the expression of HSPE mRNA due to high levels in the tibolone group. The groups differed in terms of PCNA, with lower levels found in the tibolone group followed by the estradiol benzoate + dydrogesterone group. A statistically significant positive correlation was observed for PCNA versus perlecan and MMP-9. CONCLUSIONS: There was no difference in the effects of combinations of estradiol and different progestogens on extracellular matrix components, and breast cell proliferation was associated with increases in perlecan and MMP-9.

Effect of estrogen therapy on vascular perlecan and metalloproteinases 2 and 9 in castrated rats.

AIM: To study the effects of estrogen therapy on the expression of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) and perlecan in the vascular wall. METHODS: Twenty 180-day-old Wistar rats were castrated and treated 1 week later for a period of 4 weeks with one of the following: (1) placebo; (2) 0.5 µg/day estradiol benzoate (E(2)B); (3) 5 µg/day E(2)B; (4) 50 µg/day E(2)B. A fifth group consisted of rats that had not been castrated. Following treatment, expression of MMP-2 and MMP-9 mRNA (MMP-2([RNA]) and MMP-9([RNA]), respectively) was analyzed by real-time PCR, and expression of MMP-2 (MMP-2([IH])), MMP-9 (MMP-9([IH])) and perlecan was quantified by immunohistochemistry, in carotid walls. RESULTS: There were no differences among castrated groups for MMP-2([RNA]) (p = 0.1969) and for MMP-9([RNA]) (p = 0.1828); however, a correlation was observed between E(2)B dose and MMP-9([RNA]) levels (r = 0.471, p = 0.018). Differences among groups were observed for MMP-2([IH]), MMP-9([IH]) and perlecan (p < 0.0001), wherein higher levels were observed in animals treated with estrogen therapy, correlating with E(2)B doses in the case of MMP-9 (r = 0.441, p = 0.026) and perlecan (r = 0.574, p = 0.005). CONCLUSIONS: Estrogen therapy correlates with higher levels of MMP-2, MMP-9 and perlecan in the extracellular matrix of carotid walls in castrated rats, in a dose-dependent manner. There was a dose-response effect of E(2)B on the expression of MMP-9 mRNA and, possibly, MMP-2 mRNA.

Effect of abrupt discontinuation versus gradual dose reduction of postmenopausal hormone therapy on hot flushes.

OBJECTIVE: To compare the effects of the abrupt discontinuation of postmenopausal hormone therapy (HT) and reduction of the daily dosage of the hormone on climacteric symptoms. METHODS: The study included Brazilian postmenopausal women who were using estrogen-progestogen hormone therapy in full doses previously prescribed for vasomotor symptoms. The patients were randomized to receive one of three treatments: placebo for 6 months; estradiol (E2) 1 mg/day + norethisterone acetate (NETA) 0.5 mg/day for 2 months, followed by placebo for 4 months; or E2 1 mg/day + NETA 0.5 mg/day for 4 months, followed by placebo for 2 months. The climacteric symptoms were assessed by the Blatt-Kupperman Menopausal Index at baseline and at 2, 4 and 6 months. Statistical evaluation was performed using the chi(2) or Fisher's test for categorical data, the Kruskal-Wallis test for numerical data, and ANOVA for time and group relationship with the Blatt-Kupperman Menopausal Index. RESULTS: We randomized 60 women (20 in each group), and 54 completed the study. It was observed that both the full Blatt-Kupperman Menopausal Index and the hot flush score did not change significantly in the HT group during low-dose therapy compared with baseline; however, the evaluation performed at 2 months after low-dose-HT cessation showed that the full Blatt-Kupperman Menopausal Index and the hot flush score were similar to those of the group who stopped HT abruptly and significantly higher than at baseline (hot flush scores: p < 0.001 for all three groups at months 2, 4 and 6, respectively, vs. baseline). CONCLUSION: Discontinuation of HT by reducing the daily dose of estrogen for a period of 2 or 4 months did not differ in its effect from that of abrupt cessation with regard to vasomotor symptoms.