February 5, 2001
Belatedly, we are turning some attention to the fact that there are important differences in the natural history of HIV in women compared to men. For example, women tend to have slightly lower viral loads at certain stages of disease. With the epidemic affecting an ever-larger number of women, it will be crucial to understand how gender influences the natural history of HIV, response to medication, and side effects, among other issues.
Van Benthem and colleagues asked whether hormonal influences, which change during a woman's life, influenced the rate of CD4 decline. They studied 382 women who had a known interval of seroconversion, and asked whether pregnancy or menopause affected the CD4 count. They found that pregnancy transiently lowered CD4 counts, but that this effect was temporary. This is consistent with other studies and the clinical experience of caring for HIV-infected women during pregnancy. What was more striking was that menopausal status resulted in significantly lower CD4 counts on a continual basis, despite controlling for age. Three years after seroconversion, postmenopausal women had mean CD4 counts of 333 cells, compared to 399 cells in the premenopausal women. This would be expected to be a clinically meaningful difference.
This paper leads us to pose a number of important questions. Does estrogen, progesterone or both mediate this? Would estrogen replacement therapy lead to slower decay of CD4 counts? What about the effect of estrogen therapy on the integrity of the vaginal mucosa which normally protects against infection with other STDs? Will estrogen therapy also be important to protect against accelerated osteopenia? On the negative side, will HIV interact with estrogens to increase the risk of breast or endometrial cancers? Will it effect other cancers seen in the setting of HIV such as lymphoma? I have no answers to any of these questions. These clearly remain urgent issues for clinical research over the next few years.
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