Cyproterone acetate, an alternative progestogen in postmenopausal hormone replacement therapy? Effects on serum lipids and lipoproteins

Summary. Serum lipids and lipoproteins were studied in 76 healthy postmenopausal women treated for 1 year with either oestradiol valerate sequentially combined with the anti-androgenic progestogen cyproterone acetate (CPA) or placebo. The women were examined every 3 months between days 18 and 21 of the tablet cycle, where the progestogen had been added to the oestrogen for at least 6 days. Combined oestrogen-CPA therapy resulted in significantly reduced levels of total serum cholesterol and LDL-cholesterol at all examinations, but serum triglycerides and HDL-cholesterol levels were similar in the two groups. Total serum cholesterol and LDL-cholesterol were reduced by approximately 5% ( P <0.01) and 8% ( P <0.01), respectively, after 1 year of combined oestrogen-CPA therapy in comparison with both the initial values and the placebo group but serum triglycerides and HDL-cholesterol levels were unchanged in both groups.     

Cyproterone acetate, an alternative progestogen in postmenopausal hormone replacement therapy? Effects on serum lipids and lipoproteins

Serum lipids and lipoproteins were studied in 76 healthy postmenopausal women treated for 1 year with either oestradiol valerate sequentially combined with the anti-androgenic progestogen cyproterone acetate (CPA) or placebo. The women were examined every 3 months between days 18 and 21 of the tablet cycle, where the progestogen had been added to the oestrogen for at least 6 days. Combined oestrogen-CPA therapy resulted in significantly reduced levels of total serum cholesterol and LDL-cholesterol at all examinations, but serum triglycerides and HDL-cholesterol levels were similar in the two groups. Total serum cholesterol and LDL-cholesterol were reduced by approximately 5% (P less than 0.01) and 8% (P less than 0.01), respectively, after 1 year of combined oestrogen-CPA therapy in comparison with both the initial values and the placebo group but serum triglycerides and HDL-cholesterol levels were unchanged in both groups.     

Long-term effects of percutaneous estrogens and oral progesterone on serum lipoproteins in postmenopausal women

Serum lipids and lipoproteins were examined in a group of 45 healthy postmenopausal women who were treated for 2 years with either 3 mg of percutaneous estradiol (n = 20) or placebo (n = 25). Percutaneous estradiol was given alone during the first year of treatment and in combination with oral micronized progesterone (200 mg) for 12 days of each cycle during the second year. The women were examined every 3 months throughout the 2 years. Percutaneous estrogen therapy significantly reduced total serum cholesterol and low-density lipoprotein cholesterol, whereas no significant differences were observed in serum triglycerides and high-density lipoprotein cholesterol. Addition of oral progesterone during the second year of treatment did not produce any significant alterations in serum total cholesterol or low-density lipoprotein cholesterol, both of which remained significantly reduced. Serum triglycerides remained virtually unchanged, whereas a slight but significant increase (p less than 0.05) was observed in high-density lipoprotein cholesterol levels at the end of the study period. We conclude that percutaneous estrogen administration produces changes in total serum cholesterol and low-density lipoprotein cholesterol levels similar to those observed after oral estrogen administration. However, the magnitude and time course of the response seem to be modulated by the route of administration. Addition of oral micronized progesterone does not influence the beneficial estrogenic actions on serum lipids and lipoproteins and seems to be a proper "progestogen" in percutaneous estrogen therapy.     

Lipid metabolic studies in women with a polycystic ovary syndrome during treatment with a low-dose desogestrel-ethinylestradiol combination

Twenty women with the polycystic ovary syndrome (PCO) were treated with a combination of desogestrel and ethinylestradiol (EE) and the effects on lipids and lipoproteins were compared with those induced in a group of 13 regularly menstruating, healthy women. All women were examined before and after 3 months of treatment. Compared with the regularly menstruating women, the PCO women had significantly higher body weights and blood pressure as well as elevated levels of triglycerides in serum and VLDL. During treatment, 14 out of 20 women affected by PCO lost weight. No significant change in blood pressure was observed. In the PCO group, moderate increments were encountered in serum cholesterol, phospholipids and triglycerides. No significant changes were seen in LDL-cholesterol or HDL-cholesterol. The ratio LDL-cholesterol/HDL-cholesterol did not alter. The level of total cholesterol in VLDL rose during treatment. These changes in serum and lipoprotein lipids in PCO patients were of the same type and magnitude as those found in the control group, apart from an increase in HDL-cholesterol in the latter. The only remaining difference after treatment was a slightly higher level of VLDL triglycerides in the PCO women. Thus only moderate changes were induced in lipid and lipoprotein patterns by the combination of desogestrel and EE. A "positive" influence on lipids and lipoproteins cannot be considered as a further advantage, added to the list of indications when hormonal treatment is used in PCO-affected women. The clinical implications of elevated triglycerides remain to be clarified.     

Androgen and lipid profiles in adolescents with polycystic ovary syndrome who were treated with two forms of combined oral contraceptives

OBJECTIVE: To compare the effects of cyproterone acetate and desogestrel, as part of combined oral contraceptives, on lipid metabolism and hirsutism of adolescents with polycystic ovary syndrome (PCOS). DESIGN: Prospective randomized clinical trial. SETTING: Outpatient gynecology clinic (referral center) of a university. PATIENT(S): Twenty-eight adolescent girls with clinical and biological hyperandrogenism and six or less menses during the past 12 months. INTERVENTION(S): Group A (n = 14) received 0.15 mg of desogestrel plus 0.030 mg of ethinyl estradiol daily. Group B (n = 14) received 2 mg of cyproterone acetate plus 0.035 mg of ethinyl estradiol daily. Treatment was given for 21 days followed by a 7-day rest for a period of 12 months. MAIN OUTCOME MEASURE(S): Hirsutism and lipid profile were evaluated before initiation and at 3, 6, 9, and 12 months of treatment. Androgen profile was evaluated before and at 12 months of treatment. RESULT(S): A significant decline of the Ferriman-Gallway hirsutism score was observed from the sixth month of therapy in both groups. During therapy, the levels of testosterone, free testosterone, Delta(4)-androstenedione, and 17OH-progesterone decreased significantly, whereas sex hormone-binding globulin (SHBG) increased significantly in both groups. The level of total cholesterol and low density lipoprotein (LDL) cholesterol increased significantly, whereas high density lipoprotein (HDL) cholesterol and apolipoprotein A-I increased significantly from the third month of therapy in both groups. Total cholesterol/HDL cholesterol and LDL cholesterol/HDL cholesterol ratios remained unchanged. The levels of triglycerides increased significantly in the cyproterone acetate-treated group after the third month. CONCLUSION(S): Treatment of adolescent girls with PCOS with the two studied formulations is comparably effective in decreasing hirsutism and androgen levels. Both combined oral contraceptives are associated with an increase of total cholesterol, LDL cholesterol, and HDL cholesterol levels and no change of the total cholesterol/HDL cholesterol and LDL cholesterol/HDL cholesterol ratios. Treatment with the cyproterone acetate combined oral contraceptive is associated with a tendency toward increasing the levels of triglycerides.     

Lipid effects of an intrauterine levonorgestrel device or oral vs. vaginal natural progesterone in post-menopausal women treated with percutaneous estradiol

Background: The ideal progestin for combined hormone replacement therapy should be free of adverse effects on lipid metabolism. We therefore examined lipid profiles during continuous hormone replacement therapy (HRT) with an estradiol-gel combined with either a levonorgestrel-releasing intrauterine device (LNG-IUD) or oral/vaginal natural progesterone. Methods: Sixty menopausal women recruited in this open, non-randomised parallel three-group study received percutaneous gel containing 1.5 mg of estradiol daily. Progestin was administered to the women with an LNG-IUD (n = 20), as oral natural progesterone (n = 21) 100 mg daily on the 1 – 25 calendar days of the month or as vaginal progesterone (n = 19) 100 – 200 mg daily on the 1 – 25 calendar days of the month. Serum concentrations for total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and sex hormone binding globulin (SHBG) were measured at 0, 6 and 12 months. The median (and 95% confidence interval) of the serum SHBG, total, LDL-, HDL-cholesterol and triglycerides concentrations at baseline and after 6 and 12 months of the study and the ratio of 6 and 12 months values to baseline values were calculated. Results: Total cholesterol was significantly decreased (8%) in the vaginal progesterone group at the end of the trial. HDL-cholesterol did not change in either of the progesterone groups, while a slight but transient decrease (median 15%) was seen at 6 months in the LNG-IUD group. There were no significant changes in triglycerides or LDL-cholesterol concentrations in any group. SHBG did not change significantly in the LNG-IUD and vaginal progesterone groups, while a slight but transient increase was seen in oral P group at 6 months. Conclusions: As the only significant harmful effect observed was a transient decrease in HDL-cholesterol in the LNG-IUD group at 6 months, each of these HRT-administration methods can be regarded as being safe in their effects on lipid metabolism. Received: 14 November 1997 / Accepted: 19 January 1998     

Effects of sequential combined transdermal and oral hormone replacement therapies on serum lipid and lipoproteins in postmenopausal women

The aim of this study was to compare the effects of sequential combined transdermal and oral postmenopausal hormone replacement therapies on serum lipid-lipoprotein profiles risk markers for cardiovascular disease. A prospective randomize study was designed: Ninety-six healthy nonhysterectomised postmenopausal women were randomized to receive either transdermal continuous 17β-estradiol, 0.05 mg/d (Estraderm TTS, Novartis, Basel, Switzerland), with transdermal sequential norethisterone acetate, 0.25 mg/d (Estragest TTS, Novartis, Basel, Switzerland), or oral continuous conjugated equine estrogens, 0.625 mg/d (Premarin 0.625 mg, Wyeth, Philadelphia, U.S.A.), with oral sequential medroxyprogesterone acetate, 10 mg/d (Farlutal 5 mg, Deva, Istanbul, Turkey). 84 women completed the trial, 42 in oral and 42 in the transdermal group. The serum levels of total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, apolipoproteins AI and apolipoproteins B at 6 months after starting treatment were compared with baseline values for both therapies. Both oral and transdermal therapies significantly reduced serum levels of total cholesterol (208– 190 mg/dL and 216–199 mg/dL, respectively, p=0.0001) and LDL-cholesterol (128–112 mg/dL and 140– 127 mg/dL, respectively, p=0.001). The serum levels of triglycerides did not show any significant change with oral therapy, whereas this lipid fell (128–101 mg/dL, p=0.0001) significantly with transdermal therapy. We found significant decrease in HDL-cholesterol with transdermal therapy while there was no significant change with oral therapy. Apolipoproteins AI, the major protein component of HDL₂ subfraction, was increased by oral therapy and lowered by transdermal therapy. As a conclusion, we have found that serum total cholesterol and LDL-cholesterol were lowered by both therapies, with no significant differences between treatments, whereas there were significant differences between treatments according to effects on serum triglycerides and apolipoproteins AI. Received: 15 May 2001 / Accepted: 20 July 2001     

A comparison of continuous combined hormone replacement therapy, HMG-CoA reductase inhibitor and combined treatment for the management of hypercholesterolemia in postmenopausal women.

OBJECTIVE: To compare the lipid-altering effects of hormone replacement therapy alone and in combination with HMG-CoA reductase inhibitor in postmenopausal women with hypercholesterolemia. METHODS: This was a prospective randomized controlled trial with 3 parallel groups. The patients (n = 35) were randomly assigned to receive pravastatin 20 mg/day (n = 12); continuous combined hormone replacement therapy (0.625 mg conjugated estrogen/day combined with medroxyprogesterone 5 mg/day) (n = 12); continuous combined hormone replacement therapy plus pravastatin (n = 11) for 16 weeks. RESULTS: Among patients treated with continuous combined hormone replacement therapy levels of total cholesterol (10.7%) and LDL cholesterol (12.6%) decreased significantly (p < 0.05), while levels of high density lipoprotein cholesterol (5%) and triglycerides (6.2%) increased insignificantly (p > 0.05). Patients in the pravastatin group achieved significant reductions of 18.8 and 21.4% in total cholesterol and low density lipoprotein cholesterol levels, respectively (p < 0.05). Among patients treated with a combination of continuous combined hormone replacement therapy plus pravastatin, levels of total cholesterol (20.5%) and low density lipoprotein cholesterol (23.8%) decreased the most, while levels of triglycerides (2.1%) decreased lower than the pravastatin-only group. The mean percentage of the differences between the baseline and treatment levels of the lipids and lipoproteins were not significant between the 3 study groups (p > 0.05). CONCLUSION: No significant difference between hormone replacement therapy alone and in combination with HMG-CoA reductase inhibitor in the treatment of postmenopausal women with hypercholesterolemia was noted in this study. The combination of hormone replacement therapy not only does not adversely affect the lipid-lowering effect of pravastatin alone, but hormone replacement therapy also offers additional benefits in the treatment of hypoestrogenic hypercholesterolemia in postmenopausal women.     

Eicosapentaenoic acid effect on hyperlipidemia in menopausal Japanese women. The Niigata Epadel Study Group

OBJECTIVE: To assess the efficacy and safety of eicosapentaenoic acid for the treatment of hyperlipidemia in symptomatic menopausal Japanese women. METHODS: We performed a prospective observational 48-week study in hyperlipidemic menopausal women. We randomly assigned 141 women, whose levels of serum total cholesterol were 220 to 280 mg/dL or whose serum triglycerides were 150 to 400 mg/dL at baseline to groups treated with estriol (E3) 2 mg daily (control group, n = 72) or ethyl icosapentate 1800 mg daily and E3 2 mg (eicosapentaenoic acid group, n = 69). RESULTS: Serum levels of total cholesterol decreased significantly from 249.4 to 238.6 mg/dL (-4.3%, P =.003) in the control group and from 252.3 to 234.0 mg/dL (-7.3%, P =.001) in the study group at week 48 in the women whose total cholesterol was not less than 220 mg/dL at baseline. Serum levels of triglycerides decreased significantly from 194.5 to 141.5 mg/dL (-27. 2%, P =.001) in the study group but increased slightly from 192.9 to 207.4 mg/dL (+7.5%) in the control group at week 48 in the women whose level of triglycerides was not less than 150 mg/dL. There were significant differences between these two groups at weeks 12, 24, and 48. Serum levels of total cholesterol and triglycerides were significantly decreased at week 48 in the study group regardless of whether the women were obese. There were no severe adverse effects. CONCLUSION: Combination therapy with eicosapentaenoic acid and E3 was effective and safe for menopausal women with hypertriglyceridemia.     

Lipid metabolism during treatment of endometriosis with the progestin dienogest

The effects of a new progestational compound, dienogest (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4,9-dien-3-one) on lipid metabolism have been studied in 84 otherwise healthy women with laparoscopically proven endometriosis. The women, aged 17 to 45, years were treated with 2 mg dienogest in tablet form daily for 24 weeks. The progestin was highly effective on endometriotic lesions and symptoms, showing an objective endoscopic and a subjective symptomatic improvement in 80% and 83% respectively. Triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol and the LDL-cholesterol/HDL-cholesterol ratio were determined before and after 1, 3 and 6 months use of the progestin. There was a maximum decrease of -5.8% in HDL-cholesterol and of -6.5% in triglycerides after 6 months of therapy vis-à-vis the pretreatment values. The maximum increase in LDL-cholesterol of +5.0% was recorded by the end of the first month of dienogest ingestion. The LDL-cholesterol/HDL-cholesterol ratio rose from 1.6 to 1.8 during the course of therapy. There were no significant changes. The data suggest that 2 mg dienogest has little influence on lipid metabolism and provides also in this respect a suitable approach to the hormonal therapy of endometriosis.     

The influence of 5-year therapy with tibolone on the lipid profile in postmenopausal women with mild hypercholesterolemia.

Our objective was to investigate the effects of 5-year therapy with tibolone on the lipid profile in postmenopausal women with mild hypercholesterolemia (total cholesterol, 241 +/- 7 mg/dl; LDL cholesterol, 153 +/- 9 mg/dl). Eighty-two patients were divided into two groups. Group A (53 women) received 2.5 mg of tibolone per day. Group B (29 women) received no tibolone. Total, low- and high-density lipoprotein cholesterol and lipoprotein(a) were found to be decreased in the tibolone group, by 17.7%, 32%, 15.5% and 12%, respectively (p < 0.01) throughout the 5-year treatment, while triglycerides showed no significant change. The lipid profile in the control group remained at its initial values. Menopausal symptoms disappeared in the treatment group within the first 5 months, whereas they deteriorated in the control group during the first 2 years. Although a few unwanted side-effects on hormone-dependent tissues were observed (including vaginal spotting in 11.3% and febrile hemorrhagic cystic mastopathy in 3.8%) long-term therapy with tibolone seemed to be well tolerated, and appeared to have a beneficial effect on the levels of serum lipids.     

Cyclic changes in serum cholesterol and lipoproteins following different doses of combined postmenopausal hormone replacement therapy

Cyclic changes in lipoproteins after sequential oestrogen-progestogen therapy were studied in a group of healthy postmenopausal women treated with three different hormone doses, and followed up for two consecutive cycles by twice weekly examinations (a total of 17 examinations). There was a significant rise in high density lipoprotein (HDL) cholesterol and a significant fall in low density lipoprotein (LDL) cholesterol closely related to the dose of the oestrogen component. Addition of the progestogen, 1 mg of norethisterone acetate, decreased the oestrogen-induced rise in HDL, but HDL levels remained higher than initial values in the high-dose (4 mg) and medium dose (2 mg) groups. The average increases in HDL cholesterol were 13%, 9% and 2% in the high-dose, medium-dose and low-dose (1 mg) groups, respectively, and the corresponding mean decreases in LDL cholesterol were 18%, 15% and 10% respectively. We conclude that postmenopausal treatment with sequentially combined oestrogen-progestogen has no adverse effects on the lipoprotein status.     

The action of Sequostat in comparison to Sequence Ovosiston on selected metabolic parameters]

The effects of two sequential oral contraceptive preparations, Sequostat (6 days ethinylestradiol 0.05 mg, 15 days ethinylestradiol 0.05 mg + norethisterone acetate 1.0 mg) and Sequence-Ovosiston (9 days mestranol 0.1 mg, 12 days mestranol 0.08 mg + chlormadinone acetate 2.0 mg) on triglycerides, total cholesterol, HDL- and LDL-Cholesterol, glucose tolerance, total plasma proteins, plasma protein fractions, plasma transaminases, gamma-glutamyl-transferase, alkaline phosphatase and antithrombin III were studied in two groups of 46 and 29 young women respectively. Investigations were performed prior to the hormonal intake and after treatment for 3, 6 and 12 months. In nearly all parameters studied significant but minimal changes could be demonstrated which in most cases showed a minor degree in the Sequostat-group, while Sequence-Ovosiston exerted a less effect on glucose tolerance. A significant increase of HDL-cholesterol and a reduction of LDL/HDL-cholesterol relation could be demonstrated at least in the first six months, resulting from the estrogen dominance of the contraceptives.     

Continuous oestrogen-progestogen treatment and serum lipoproteins in postmenopausal women

Summary. Serum lipids and lipoproteins were examined in 44 healthy postmenopausal women every 3 months during 1 year of treatment with either continuous oestrogen-norethisterone acetate or placebo. Total serum cholesterol and LDL-cholesterol levels were reduced by approximately 15% and 20% ( P <0.001), respectively in the hormone group but were unchanged in the placebo group. Serum triglycerides levels remained constant in both groups. HDL-cholesterol levels were significantly reduced by approximately 10% in the hormone group but significant reductions of 5–10% also occurred in the placebo group so that differences between the two groups were only significant after 3 months of treatment. Vaginal bleedings were experienced during the first 3 months by eight of the 21 women receiving hormones, but in only one woman after 9 months of therapy. The addition of norethisterone acetate to postmenopausal oestrogen therapy in clinically relevant doses had no adverse effects on lipoproteins as previously reported, even though administered continuously. Moreover, the low frequency of bleeding with continuous oestrogen-progestogen therapy would make this an appropriate alternative in postmenopausal replacement therapy.     

Menoflavon and lipid profile in menopausal women

The purpose of the study was to assess the effect of Menoflavon on plasma lipoprotein levels in menopausal women. Twenty-eight female patients were examined and treated. After a 3-month treatment, the authors established a reduction of the total plasma cholesterol levels by 7.15%. This reduction was more considerable (by 11.45%) in the females presenting with higher risk values (> 6.20 mmol/L). After a 6-month treatment, however, the subsequent cholesterol reduction was insignificant and the plasma levels were stabilized. Menoflavon therapy diminished plasma LDL-cholesterol levels by 8.71% after a 3-months long course and by 9.5% after a 5-months long one in comparison with the initial levels. Menoflavon did not exert any effect on the plasma levels of HDL-cholesterol and triglycerides as well.     

Plasma lipid profile in gynecologic cancers

BACKGROUND: Lipids are associated with cancer because they play a key role in the maintenance of cell integrity. We studied the relationship of plasma lipids with gynecologic cancer. METHODS: A total of 196 female individuals were included in the study. Of these 50 were normal subjects. The remaining were cancer patients: 80 breast cancer, 40 ovarian cancer and 26 patients with other gynecologic cancers. Plasma levels of triglycerides, total cholesterol, LDL-cholesterol and HDL-cholesterol were estimated by using spectrophotometer. RESULTS: In breast cancer patients there is moderate increase in the plasma levels of triglycerides (18%) and cholesterol (21%), and a high increase in LDL-cholesterol (43%), while there is a moderate decrease in HDL-cholesterol levels (30%) when compared with normal subjects. In ovarian cancer patients, there is a high decrease in the plasma levels of triglycerides (31%) and HDL-cholesterol (39%), while a moderate decrease in cholesterol (28%) and LDL-cholesterol levels (11%) when compared with normal subjects. In gynecologic cancers other than breast and ovarian cancer, there is a moderate decrease in plasma levels of the triglycerides (25%), cholesterol (21%), and HDL-cholesterol levels (27%), while a non-significant decrease in LDL-cholesterol (6.2%) when compared with normal subjects. CONCLUSIONS: Plasma lipid levels, except HDL-cholesterol, are raised in breast cancer and are decreased in other gynecologic cancers. HDL-cholesterol is decreased in all gynecologic cancers. As there is an alteration in the plasma lipid profile during gynecologic cancers, it may be helpful for diagnosis of the disease.     

Lipid effects of hormone replacement therapy with sequential transdermal 17-beta-estradiol and oral dydrogesterone

OBJECTIVE: To assess the effects on lipid and lipoprotein levels of a combination therapy of matrix patch and oral sequential dydrogesterone. METHODS: The lipid effects of transdermal estradiol (E2) (80 microg/day continuously) and oral dydrogesterone (10 mg from days 15-28 of each cycle) were assessed in a multicenter, prospective, open, baseline-controlled study. Subjects were 42 healthy, postmenopausal women who had not had hysterectomies. Fasting blood samples were taken at baseline, day 14 of cycle 3 (estrogen alone), and day 25 of cycle 6 (estrogen and progestogen). The main outcome measures were changes from baseline in total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides after six cycles. RESULTS: Thirty-six subjects completed six cycles and in the 28 with complete data, HDL cholesterol increased by 10.6% from 65.25 to 72.2 mg/dL (95% confidence interval [CI] 2.32, 11.58, P = .005) and LDL cholesterol fell by 5.1% from 130.9 to 124.3 mg/dL (95% CI 13.9, 1.16, P = .07). There was a nonsignificant decrease in LDL cholesterol from 130.9 at baseline to 124.3 mg/dL at 6 months and in triglycerides from 110.6 to 107.1 mg/dL. CONCLUSION: Sequential treatment with transdermal E2 and oral dydrogesterone increased HDL cholesterol, without the accompanying increase in triglycerides that occurs with oral estrogen replacement therapy.     

Effects of gestrinone on serum lipid and lipoprotein levels in women with endometriosis

Gestrinone (G) was given to 12 females with endometriosis in weekly doses of 5 or 10mg for 4 to 6 months, and the change in serum lipids and lipoproteins was analysed. G decreased total cholesterol by 20% (p less than 0.05), triglycerides by 36% (p less than 0.05), phospholipids by 28% (p less than 0.01) and lipid peroxides by 34% (p less than 0.05), among which reductions in them were statistically significant when compared with the pretreatment levels. Levels of high density lipoproteins (HDL) also fell: HDL-cholesterol by 41% (p less than 0.01), HDL-triglycerides by 49% (p less than 0.05) and HDL-phospholipids by 38% (p less than 0.01) which were significant. Concurrently apolipoproteins (Apo) and lecithin-cholesterol acyltransferase activity (LCAT) decreased: Apo A-I by 31% (p less than 0.01), Apo A-II by 13% (p less than 0.05) and LCAT by 53% (p less than 0.05), which were significant. In contrast, there were few changes in the levels of low density lipoproteins (LDL) and Apo B. There was also little effect on very low density lipoproteins (VLDL) except VLDL-triglycerides which decreased by 52% (p less than 0.05). Meanwhile free fatty acids increased by 61% (p less than 0.05). Therefore, the atherogenic index defined as the ratio of LDL-cholesterol to HDL-cholesterol rose as much as 92% (p less than 0.01) of the initial value in 24 weeks of medication. When these results were examined with respect to the 5 and 10mg administration group, dose-dependent effects were observed, but these were not marked.(ABSTRACT TRUNCATED AT 250 WORDS)     

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

OBJECTIVE--To study the effect of long-term continuous combined oestrogen/progestogen therapy on calcium metabolism, lipoproteins, and bleeding pattern in early postmenopausal women. DESIGN--A prospective, open, controlled study. After initial examinations, control examinations were performed every three months for the first two years and every year for the following three (two) years, with determinations of bone mass, serum lipoproteins, and bleeding pattern. SETTING--Out-patient research clinic at The Department of Clinical Chemistry, Glostrup Hospital, Denmark. PARTICIPANTS--Eighteen healthy women between 6 months and 3 years after a natural menopause, entered in a trial of continuous long-term hormone replacement therapy and a comparison group of 19 age-matched untreated women. INTERVENTION--The treated group received 2 mg of 17 beta-oestradiol combined with 1 mg of norethisterone acetate orally each day continuously for 5 years with a 3 month therapy-free interval after the first 2 years. The women were investigated before treatment, then every 3 months for the first 2 years and every year for the next 3 years for determinations of bone mass, serum lipoproteins and bleeding patterns. The comparison group was followed-up in parallel for the first 4 years. Forearm bone mass was measured with single photon absorptiometry. Blood and urine samples were taken in the morning after an overnight fast and tobacco abstinence. MAIN OUTCOME MEASURES--The effects of hormone therapy on bone mineral content in the forearm, on serum and urine indices of calcium metabolism, on serum levels of total, high (HDL-C) and low (LDL-C) density lipoprotein cholesterol, and bleeding pattern. RESULTS--Bone mineral content in the forearm was stable during the 5 years of treatment, whereas it declined significantly averaging 10% after 4 years in the comparison group. The biochemical estimates of bone turnover decreased to premenopausal level in the hormone group, whereas they remained at a high level in the comparison group. In the hormone group total cholesterol and LDL-C decreased by 20% whereas HDL-C was virtually unchanged. The treatment was associated with minor irregular bleeding in nine women during the first 6 months of treatment, after which no bleeding was experienced. CONCLUSION--Continuous combined oestrogen/progestogen therapy can keep early postmenopausal women free of bleeding episodes for a period of 5 years, after the first 6 months in which spotting occurs in 25%. The therapy prevented bone loss completely. The changes in serum lipoproteins were concordant with a lipid profile associated with a decreased risk of coronary heart disease.     

Effect of cyclic estrone sulfate treatment on lipid profiles of postmenopausal women with elevated cholesterol levels

The effects of two doses of cyclic unopposed estrone sulfate therapy on the lipid profiles of 153 healthy postmenopausal women with baseline total cholesterol levels above 219 mg/dL were compared in a multicenter, double-blind, placebo-controlled study. Patients were assigned randomly to one of three treatment groups: estrone sulfate 0.625 mg (N = 59) or 1.25 mg (N = 43), or placebo (N = 51). The median baseline total cholesterol levels of the three treatment groups were 262, 269, and 262 mg/dL, respectively. Total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and the HDL/LDL ratio were assessed after 6, 9, and 12 months of treatment. There was a significant monotonic dose-response relationship of estrone sulfate in raising HDL levels, lowering LDL levels, and raising the HDL/LDL ratio at all intervals measured. These results indicate that estrone sulfate is effective in creating a beneficial change in the lipid profile of postmenopausal women with elevated baseline total cholesterol.