Phasic serum lipid excursions occur during cyclical oral conjugated oestrogens but not during transdermal oestradiol sequentially combined with oral medroxyprogesterone acetate.
BACKGROUND AND OBJECTIVE: Recent data indicate that oral medroxyprogesterone acetate (MPA) has limited unfavourable, neutral or even favourable effects on serum lipid fractions when added to oestrogen replacement therapy. The purpose of this study was to evaluate the serum lipid fractions at the beginning and at the end of each phase of a sequentially combined replacement cycle comparing the oral and the transdermal routes of oestrogen administration. DESIGN: Randomized study with a matched control group. Oral conjugated oestrogens (OCE, 0.625 mg) or transdermal oestradiol (TE 50 micrograms) was taken from day 1 to day 25 and MPA (5 mg) added on days 14 to 25. Serum lipids were evaluated on days 1, 14 and 25 of monthly replacement cycles. PATIENTS: The early post-menopausal women in the control group (n = 11) and in the treatment groups (OCE/MPA, n = 15; TE/MPA, n = 17) were evaluated every 3 months for 12 months and every 6 months for another 12 months. MEASUREMENTS: Serum levels of triglycerides (TG), cholesterol (C) fractions and apolipoproteins (Apo) and their respective ratios were measured at months 1, 3, 6, 9, 12, 18, 24. Menopausal symptoms and uterine bleedings were evaluated in parallel and an endometrial biopsy was performed at the end of the 12th and 24th months of treatment. RESULTS: After 14 days of OCE, C, LDL-C, and Apo B were decreased and TG, HDL-C and Apo A1 were increased. The sequential addition of MPA accentuated the reduction of LDL-C and Apo B but attenuated the elevation of TG, HDL-C and Apo A1. These changes tended to revert toward baseline during the period free of medication. By contrast, at the end of 14 days of TE there was a non-significant reduction in TG and LDL components and a limited increase in HDL-C and Apo A1. During the subsequent addition of MPA there was no significant decrease in TG, LDL-C or Apo B but an elimination of the increase in HDL components. These combined changes resulted in a significant reduction in the LDL-C/HDL-C ratio and a significant elevation in the Apo A1/Apo B ratio only in the OCE/MPA group. CONCLUSION: Overall, oral conjugated oestrogens induced favourable intragroup changes in cholesterol fractions whereas transdermal oestradiol maintained serum lipids at levels not different from baseline. The sequential addition of oral medroxyprogesterone acetate attenuated the beneficial elevation of HDL, did not affect the beneficial effect of oestrogens on ratios of cholesterol fractions and attenuated the unfavourable effect of oral conjugated oestrogens on triglycerides. The partial loss of beneficial effects on lipoproteins during cyclical interruption of hormone therapy would be an argument in favour of the evaluation of continuous regimens of oestrogen/progestagen replacement.