Estrogen replacement therapy in combination with continuous intrauterine progestin administration reduces the amount of circulating oxidized LDL in postmenopausal women: dependence on the dose of progestin.
BACKGROUND
Oxidized low density lipoprotein (LDL) plays a key role in processes leading to atherosclerosis. Recent studies show that LDL oxidation in vitro is effectively prevented by estrogen. Yet, the effect of hormonal therapy (HT) on in vivo LDL oxidation has remained open.


OBJECTIVE
We used a novel methodology for the measurement of oxidized LDL in vivo in order to investigate the effects of HT.


METHODS
The subjects were derived from two separate trials. In trial 1 (24 months) women (n = 32) used intra-uterine system releasing 10 micrograms/day levonorgestrel, and 2 mg oral estradiol. Trial 2 (12 months) consisted of two groups of subjects. One group (n = 30) used an intrauterine system releasing 20 micrograms/day levonorgestrel, and 2 mg estradiol; the other group (n = 32) received orally a combination of 1 mg norethisterone acetate and 2 mg estradiol. Blood samples were taken at 6 months intervals. Estimation of in vivo LDL oxidation was based on determination of baseline diene conjugation in isolated LDL.


RESULTS
Hormonal therapy in trial 1 decreased markedly in vivo LDL oxidation. The effect was seen after 6 months' HT and became more pronounced towards the end of study (41% decrease; P < 0.0001). Contrary to this, in trial 2 the two different kinds of hormonal therapy schemes did not affect in vivo LDL oxidation.


CONCLUSIONS
The strong effect seen in trial 1 shows that intrauterine levonorgestrel with 2 mg estradiol can lower LDL oxidation in vivo. The results show that this effect depends on dosage of the progestin.
Ahotupa
Markku
M
MCA Research Laboratory, Department of Physiology, University of Turku, Turku, Finland. markku.ahotupa@utu.fi
Rauramo
Ilkka
I
Vasankari
Tommi J
TJ
Skouby
Sven O
SO
Hakonen
Tiina
T
D015992:Body Mass Index; D003271:Contraceptive Agents, Female / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000097:blood*; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood / Q000187:drug effects*; D011372:Progestins / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D016896:Treatment Outcome; D014599:Uterus / Q000187:drug effects
D003271:Contraceptive Agents, Female; D008077:Lipoproteins, LDL; D011372:Progestins; C099252:oxidized low density lipoprotein; D004958:Estradiol; D016912:Levonorgestrel