Estrogen Quickly Reduces Lipoprotein (a) - One Of The "Bad Cholesterols" - But "How" Remains A Mystery

September 11, 1997

DALLAS, Sept. 23 -- Estrogen replacement therapy used to help relieve menopausal symptoms quickly reduces the amount of lipoprotein (a), one of the "bad cholesterols" in the blood, say researchers reporting in this month's American Heart Association's journal Arteriosclerosis, Thrombosis and Vascular Biology.

Estrogen replacement taken orally reduces the amount of Lp (a) within a week, and the maximum effect was seen after three weeks. The estrogen also increases the amount of high-density lipoprotein (HDL), the so-called "good cholesterol," say researchers at the Columbia University College of Physicians and Surgeons in New York.

The method of reducing this form of cholesterol differs physiologically from reduction of other low-density lipoproteins (LDLs) but the researchers aren't sure why, notes Lars Berglund, M.D.., co-author of the study.

If scientists can understand the process it would help them design drugs to reduce the risk of heart disease by reducing the Lp (a) without notable side effects. Anabolic steroids reduce Lp (a), but these can have serious adverse reactions. A possible therapy available now is niacin, but niacin also has problems with side effects in some individuals.

Estrogen taken in low doses eases the physical problems associated with menopause, including osteoporosis, a condition in which bones become porous and brittle. The therapy remains somewhat controversial because higher doses have been linked with endometrial cancer.

"Lp (a) is a form of cholesterol influenced by genetics," Berglund says. Levels are stable over time within individuals, although they can vary greatly from one person to another. The stability is an advantage in studying the protein because the natural level acts as a baseline for tests and the effects of any drug are easier to see.

Earlier tests using estrogen on men suffering from advanced prostate cancer showed a dramatic 50 percent reduction in Lp (a) when they took estrogen as treatment.

In the Columbia study, 15 healthy, post-menopausal women with an average age of 55 were given either four weeks of estrogen replacement therapy or a placebo in a randomized double-blind study. After the initial cycle, the dosages were reversed: the women who had the estrogen received the placebo and the other women the estrogen. Within one week the amount of Lp (a) in the blood of 14 of the 15 women was significantly reduced with the estrogen pills. The reduction continued until the third week when it leveled off.

There were no adverse effects from the estrogen replacement therapy, the article stated.

The Lp (a) finally was reduced by an average of 23 percent. The women represented three racial or ethnic groups and although the number of subjects was too small to test for differences among them, the effects appeared to be equal for all the women.

The effectiveness of estrogen on the other forms of cholesterol was different, Berglund says. Reductions didn't happen as quickly, hinting that they were subjected to different mechanisms.

"Further studies are warranted to elucidate the mechanisms behind the estrogen-induced changes," the report concludes.

The other two authors of the paper were Catherine H. Tuck, MD. and Stephen Holleran.
Media Advisory: Dr. Berglund can be reached at (212) 305-2068.

Reporters may call (214) 706-1396 for copies of his journal report. (Please do not publish telephone numbers.)

American Heart Association

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