Effect of hormone replacement therapy on lipoprotein(a) and lipid levels in postmenopausal women. Influence of various progestogens and duration of therapy.

BACKGROUND: Estrogen replacement therapy in postmenopausal women reduces the risk of coronary artery disease. One of the possible mechanisms of this effect is the modification of lipid profiles. However, there is controversy concerning the effects on lipoprotein(a) [Lp (a)] and lipid levels of progestogens administered with estrogen. METHODS: Five hundred fifty-one postmenopausal women were divided into 5 groups: group 1, 0.625 mg of conjugated equine estrogen (CEE) (n = 140); group 2, 0.625 mg of CEE plus 5 mg of medroxyprogesterone acetate (MPA) (n = 97); group 3, 0.625 mg of CEE plus 10 mg of MPA (n = 109); group 4, 2 mg of estradiol valerate plus 0.5 mg of norgestrel (n = 134); and group 5, control (n = 71). The Lp(a) and lipid levels were measured before and 2, 6, and 12 months after hormone replacement therapy. RESULTS: Estrogen replacement therapy for 12 months lowered the Lp(a) level by 37.1%. The addition of progestogen attenuated the Lp(a)-lowering effect of estrogen. The high-density lipoprotein cholesterol (HDL-C) level was markedly increased in group 1 (16.5%), was moderately increased in groups 2 (10.8%) and 3 (11.3%), and was not changed in group 4. The low-density lipoprotein cholesterol level was decreased by 10.9% to 17.6% in all the treatment groups. Estrogen replacement therapy for 2, 6, and 12 months raised the HDL-C level by 7.2%, 17.4%, and 17.8%, respectively. In the group with combined estradiol plus norgestrel therapy, the HDL-C level was decreased after 2 months and was not changed after 6 and 12 months. The groups that received CEE plus MPA showed intermediate effects between the group that received CEE only and the group that received estradiol plus norgestrel. CONCLUSIONS: Combined estrogen and progestogen therapy may have effects on the heart different from those of estrogen therapy alone because of adverse impact of progestogens on Lp(a) and HDL-C levels. The effects of progesterones were dependent on the androgenic potency of progestogen and the duration of therapy.

Changes in Lp(a) lipoprotein and lipid levels after cessation of female sex hormone production and estrogen replacement therapy.

OBJECTIVE: To investigate the serial changes in Lp(a) lipoprotein levels with the loss of female sex hormones by surgical menopause and with estrogen replacement therapy in the same woman. PATIENTS AND METHODS: Forty-four premenopausal women who underwent a transabdominal hysterectomy (TAH) because of benign gynecological disorders were divided into two groups: women who underwent a TAH and unilateral salpingo-oophorectomy (n=31) and women who underwent a TAH and bilateral salpingo-oophorectomy (n=13). In the group of women who underwent a TAH and bilateral salpingo-oophorectomy, 0.625 mg of conjugated equine estrogen was given daily 2 months after the operation. The levels of Lp(a) lipoprotein and lipids were measured before and at 2 and 4 months after the operation. RESULTS: In the group of women who underwent a TAH and bilateral salpingo-oophorectomy, the mean (+/-SD) concentration of Lp(a) lipoprotein was increased by 24.5% from 0.48+/-0.47 mmol/L (18.4+/-18.3 mg/dL) to 0.59+/-0.54 mmol/L (22.9+/-21.0 mg/dL) after 2 months (P<.05), and it was reduced by 30.6% to 0.41+/-0.51 mmol/L (15.9+/-20.1 mg/dL)(P<.005) with therapy with conjugated equine estrogen (Premarin). The Lp(a) lipoprotein levels were not changed in the group of women who underwent a TAH and unilateral salpingo-oophorectomy. In the group of women who underwent a TAH and bilateral salpingo-oophorectomy, the high density lipoprotein cholesterol level showed a trend of increase after 2 months from 1.45+/-0.48 mmol/L (56.1+/-18.5 mg/dL) to 1.58+/-0.309 mmol/L (61.2+/-15.1 mg/dL) without statistical significance, and it revealed a significant elevation to 1.76+/-0.43 mmol/L (68.2+/-16.8 mg/dL) with therapy with conjugated equine estrogen (Premarin) compared with that of the basal level (P<.05). CONCLUSIONS: tHE Lp(a) lipoprotein levels appear to be closely associated with female sex hormones. This association might play a pivotal role in postmenopausal increases of atherosclerotic diseases and cardioprotective effect of estrogen in postmenopausal women.

Influence of menopause on high density lipoprotein-cholesterol and lipids.

It has been generally accepted that high density lipoprotein cholesterol (HDL-C) level decreases with menopause in women. However, recent reports show different results. There is very little data concerning perimenopausal women. To verify these findings, lipids and lipoprotein(a) [Lp(a)] levels were compared among pre-, peri- and postmenopausal women of similar mean ages. Postmenopausal women had higher HDL-C levels than premenopausal women (p<0.001) and there was no difference between peri- and postmenopausal women. LDL-C level in perimenopausal women was lower than in postmenopausal women (p<0.001) and higher than in premenopausal women with borderline significance (p=.051). Total cholesterol levels showed stepwise elevation from premenopause to postmenopause. Perimenopausal women had lower Lp(a) levels than postmenopausal women (p<0.0005) and similar levels to premenopausal women. Lp(a) levels between 0.1 to 10.0 mg/dL were the most prevalent in pre- and perimenopausal women, and those between 10.1 to 20.0 mg/dL in postmenopausal women. In conclusion, menopause itself is associated with the elevation of HDL-C level, and the postmenopausal increase of coronary artery disease is not related to postmenopausal change of HDL-C level. Perimenopausal status, although transient, may favor Lp(a) and lipid profiles for delaying atherosclerosis.

National cholesterol treatment guidelines in Korean population--setting-up the cutpoints for high blood cholesterol.

National Cholesterol Treatment Guidelines are different according to race and country, and change year by year, because the distribution of lipid and lipoprotein levels are different by genetic background, dietary habit and life style. So it is mandatory to set-up the national cholesterol treatment guidelines based on the epidemiologic results. To establish the cutpoints for hypercholesterolemia specific to the Korean population, we selected the laboratories, whose inaccuracies of cholesterol measurement were less than 5%, in the external laboratory quality assessment survey, and performed epidemiological survey on the distribution of cholesterol levels, and other risk factors of coronary heart disease (CHD). As a result, prevalence of CHD risk factors was very high in hypertension (28.0%) and relatively low in diabetes (2.8%). Smokers were 42.6% of total subjects. Thirteen percent of subjects had a family member(s) who was suffering from or had of hypertension, stroke, and heart diseases. The average cholesterol level of a Korean was 187 mg/dL, which was about 25 mg/dL lower than that of United States. The 75th percentile to total cholesterol was 210 mg/dL and 90th percentile 235 mg/dL. The cutpoint for borderline-high cholesterol levels provide a major guideline for initiation of dietary and exercise therapy. We propose the cutpoint for borderline-high cholesterol levels as 200 instead of 210 mg/dL to initiate more active dietary and exercise therapy, and we also propose the temporary cutpoint for high blood cholesterol levels as 240 mg/dL instead of 235 mg/dL, which is a reasonable cutpoint considering medical insurance policy of the country. In conclusion, we suggest the cutpoints for borderline-high and high serum cholesterol levels as 200 and 240 mg/dL, respectively.

The frequency distribution of cardiovascular diseases in 13 hospital admitted patients in Korea. Korean Society of Circulation.

The frequency distribution of cardiovascular disease are changing recently due to the development of living environment. Unfortunately there are few epidemiological studies of cardiovascular diseases in general population, we tried to estimate the recent trend of cardiovascular diseases studying hospitalized patients in nationwide 13 large hospitals during a year of 1985. The hypertensive disease (24.1%) was the most common cardiovascular disease and the next were cerebrovascular disease (15.8%), arrhythmias (12.2%), ischemic heart disease (9.7%), congenital heart disease (9.1%), and rheumatic heart disease (5.4%) in order. This results showed that hypertensive disease and cerebrovascular disease are still the major cardiovascular disease and ischemic heart disease and arrhythmias are increased. But chronic rheumatic heart disease is declined compared with previous studies in hospitalized patients.