Are fixed-dose oestrogen/progestogen combinations ideal for all HRT users?

Article Abstract:

During menopause the ovaries stop making the hormone estrogen. Estrogen is known to protect women from excessive absorption of bone (osteoporosis) and from heart disease. Lack of estrogen can cause hot flashes, night sweats, and vaginal dryness, and replacement therapy can reduce these menopausal symptoms. However, estrogen may cause the cells lining the uterus to grow rapidly (proliferative endometrium), increasing the risk for endometrial cancer. Therefore, progesterone can be given in combination with estrogen to reduce the risk of endometrial cancer, while allowing the beneficial effects of estrogen replacement to continue. However, the addition of progesterone reduces the beneficial effects that estrogen has on the ratio of high density lipoproteins (HDL) and low-density lipoproteins (LDL), a predictor of arterial heart disease. Therefore, the lowest dosage of progesterone needed to reduce the side effects of estrogen is preferred. Examination of a small sample of cells lining the uterus (endometrial biopsy) can be used to determine hormonal levels. The minimal dose of progesterone required to prevent endometrial changes was studied using results of 197 endometrial biopsies obtained from women receiving different combined estrogen and progesterone hormone therapy regimens. As the dose of progesterone increased, the percentage of proliferative endometrial cells decreased. However, proliferative endometrium was observed in six percent of the women receiving the highest dose (500 micrograms of norestrel), and in three percent of the women receiving a lower 2.5 milligram dose of norethisterone. When progesterone was increased from 75 micrograms to 150 micrograms, the proliferative endometrium was reduced from 27 percent to 4 percent. Increasing dosage to 500 micrograms did not offer additional improvement. Four women developed mild atypical hyperplasia, abnormal rapid growth of endometrium. However, no one dosage regimen produced the same changes in every patient. The best dosage regimen for each individual should be determined by serial endometrial biopsies, or by determining the day in which bleeding occurs. Bleeding should occur after the progesterone is stopped (around day 11). Women bleeding between the 6th and 10th day, which was associated with proliferative endometrium, should have progesterone levels increased. (Consumer Summary produced by Reliance Medical Information, Inc.)

Dosage and administration, Progesterone

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Five years with continuous combined oestrogen/progestogen therapy. Effects on calcium metabolism, lipoproteins, and bleeding pattern

Article Abstract:

The long-term effects of continuous treatment with a combined regimen of the hormones, estrogen and progestogen, were assessed in 18 women who started treatment six months to three years after menopause. Specifically, the effects of hormone therapy on the bone mineral content; blood levels of high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C); and bleeding patterns were examined. The results were compared with the data from the same tests performed on 19 women of similar age who received no treatment. The bone mineral content did not alter in five years of hormone therapy, but decreased by 10 percent among untreated women after four years. Bone metabolism returned to normal rates in treated women, but remained high among women receiving no hormone therapy. Hormone treatment was associated with a 20 percent decrease in total cholesterol and LDL-C, but no changes in HDL-C; these alterations in lipoproteins decrease the risk of cardiovascular disease. Hormone therapy caused minor irregular bleeding in nine women during the initial six months of therapy, but bleeding ceased thereafter. The results show that continuous combined estrogen/progestogen treatment eliminated bleeding for five years in early postmenopausal women, causing spotting or minor bleeding in only 25 percent of women in the first six months. In addition, this combined hormone regimen prevented bone loss and altered lipoproteins to protect against cardiovascular disease. (Consumer Summary produced by Reliance Medical Information, Inc.)

Uterine bleeding, Uterine hemorrhage

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Endometrial, physical and psychological effects of postmenopausal oestrogen therapy with added dydrogesterone

Article Abstract:

The effects of two different doses of the progestogen dydrogesterone added to 1.25 milligrams (mg) daily of horse-derived estrogen for treating menopause were assessed in 16 postmenopausal women. Specifically, effects of dydrogesterone on microscopic tissues of the endometrium (the inner lining of the uterus); vaginal bleeding; symptoms of menopause; and psychological status were examined. One group received 20 mg per day of dydrogesterone for 12 days each month for three months, followed by the addition of 10 mg per day dydrogesterone for a further three months. The other group received the two different doses in reverse sequence. A dose of 20 mg dydrogesterone caused uniform, late secretory transformation of the endometrium, whereas the 10 mg dose of the progestogen caused either mixed early and late secretory changes or late secretory changes that are associated with atypical hyperplasia (abnormal cell proliferation). Both doses of dydrogesterone caused withdrawal bleeding that tended to be normal or spotty. Heavy bleeding was rare, and only one incidence of breakthrough bleeding occurred. Both doses caused similar bleeding patterns. This combined hormone treatment was associated with improvements in anxiety, and physical and psychological status within a three-month period; both dydrogesterone doses had similar effects. The findings suggest that the addition of this progestogen does not counteract the beneficial effects of estrogen. (Consumer Summary produced by Reliance Medical Information, Inc.)

Psychological aspects, Abnormalities, Medical examination, Endometrium, Dydrogesterone

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