HRT may still be a viable option for younger women

Studies conducted in monkeys suggest younger women could benefit from the therapy.

Current evidence suggests that hormone replacement therapy and estrogen therapy may be beneficial in younger women even though they appear harmful in older women, said Thomas Clarkson, DVM, Wake Forest University, during the Red Dress Symposium at the American Heart Association Scientific Sessions 2004.

Clarkson said a prevention strategy focused on the vascular level would begin when women were approximately 55 years of age, where the inhibitory effects of estrogen could be as high as 50% to 70%.

“We should begin with the small fatty streaks and small plaques, which all women have at the time of the perimenopausal transition, and then prevent them from becoming larger and thicker plaques,” Clarkson said.

Clarkson said the adverse events associated with estrogen among women older than 65 may be due to the upregulation of matrix metalloproteinases by estradiol. These matrix metalloproteinases are distributed in the shoulder region of the fibrous cap, which Clarkson said is there to “separate the gruel that’s in the base from the plaque in the blood.”

Thomas Clarkson

Scientists have known that the genes that control the production of matrix metalloproteinases are markedly upregulated by estradiol, Clarkson said. Increases of estradiol have been observed in the endometrium with each follicular phase of the menstrual cycle.

“It finally dawned on us cardiovascular biologists to ask if the same thing could be going on in the arteries, and it appears the answer is yes,” Clarkson said.

Clarkson and colleagues tested this idea among menopausal monkeys that were made surgically menopausal. Hormone replacement therapy was begun immediately. Clarkson said researchers observed a 70% inhibition of coronary artery atherosclerosis progression.

By contrast, when hormone treatment was delayed in the same type of monkey for a period equivalent to six postmenopausal years, no benefit was noted in the coronary arteries.

The KEEPS (Kronos Early Estrogen Prevention Study) trial was launched on April 20, 2004, and will eventually enroll 720 patients from eight clinical sites. Patients must be healthy perimenopausal women aged 40 to 55. Patients will be randomized to one of three arms: an oral estrogen tablet and placebo skin patch arm, a placebo tablet and estrogen skin patch arm, or a control arm. Researchers will examine atherosclerosis progression at varying intervals.

Clarkson also conducted another trial with monkeys in the perimenopausal stage. “It may be surprising to you that what we chose to use was psychosocially stressed monkeys, because psychosocially stressed monkeys and psychosocially stressed women have the same kind of ovarian dysfunction that women have during the perimenopausal transition,” Clarkson said.

Researchers noted that monkeys who received estrogen perimenopausally had an 88% inhibition in their coronary artery atherosclerosis. “So it seems that the perimenopausal transition is a time when coronary arteries are very affected by estrogen deficiency and the time in which they derive the most benefit from therapy.” – by Jeremy Moore

For more information:

• Clarkson TB. Have we heard the last of the hormone replacement therapy? Presented at the American Heart Association Scientific Sessions 2004. Nov. 7-10, 2004. New Orleans.