I recently posted three “Basics”-style blurbs about menopause and hormone therapy (HT). If you missed it, they are here, here, and here. The field has gone through a lot of upheaval since the WHI studies in 2002, and I would just like to share my thoughts on how to approach where we stand now. These are the sorts of questions and considerations that researchers and health care professionals need to keep in mind when they evaluate HT. After the reference-heavy previous posts this one is going to just be my thoughts, and very off-the-cuff at that.
We, as humans, have a tendency to put things in conceptual boxes. Cholesterol bad. Eggs bad. No wait eggs good. Hormone therapy good. No wait hormone therapy bad. Unfortunately, endocrinology doesn’t like boxes. Hormones abhor predictability. In fact endocrinology is a frakkin’ nightmare even when you’re dealing with one simple feedback loop. So when you hear that “estrogen is bad again” in the news, STOP.
Firstly, in the world of hormone therapy, there is no singular hormone therapy. There are different formulations of estrogen or progesterone. They each have different affinities for the various receptors they target. They each activate their receptors in different ways. They all clear out of the body differently. There is no singular dosage. There is no singular route of administration, which can also dramatically affect bioavailability and clearance. We simply cannot draw conclusions from a study of one singular therapy and then extrapolate them to all forms “hormone therapy”. One estrogenic compound is NOT representative of all other estrogenic compounds. Medroxyprogesterone acetate (MPA, or Provera) is DEFINITELY NOT like natural progestin.
Secondly, watch your study population closely. A recent paper suggested that surgically menopausal women may benefit from immediate administration of Premarin, for a duration of 7 years or so, by showing less signs of atherosclerosis. What does this study tell us? That surgically menopausal women’s arteries benefit from the administration of Premarin. These results do not necessarily apply to osteoporosis, or breast cancer. These results are not generalizable to women with intact uteri receiving Premarin/Provera, as Provera may very well counteract the beneficial effects of Premarin as in the WHI studies. However, other formulations of progesterone may do nothing or enhance estrogen’s effects.
Does your study population look at naturally menopausal women or surgically menopausal women? That will affect the hormone therapy being used. Studies of surgically menopausal women tend to have MUCH younger sample populations, and the sudden loss of circulating estrogen and progesterone is a shock to the system, as opposed to the gradual cessation that takes place over many years in perimenopause. Is your study population highly symptomatic or asymptomatic following menopause? Believe it or not, women who experience fewer hot flashes and the like can respond differently to HT than women who experience many symptoms. Does your study population have a large number of risk factors for various diseases of aging? These risk factors may impact HT negatively, especially if it has been a number of years since menopause.
Second-and-a-halfly, what’s your outcome? Estrogen can be beneficial for preventing bone loss, but it also causes breast and uterine cancer when there’s no progesterone to oppose it. Don’t generalize a beneficial effect of a particular HT to all outcomes; organ systems can and do respond very differently.
Thirdly… WHEN you receive HT matters. It matters A LOT. The WHI trials showed us that when there is a large gap between menopause and treatment initiation, there is an increased incidence of some rather serious health risks (but only when on Prempro, not necessarily applicable other formulations!). Newer studies and also animal studies suggest that if you want to maximize benefit from HT, you need to take it at menopause or shortly thereafter. The “window of opportunity” to benefit from HT does close. The specific therapy and duration of exposure is something to discuss with your physician, as each woman has different needs with regards to cardiovascular, skeletal, and mental health.
When dealing with HT, nothing is as it seems in a headline. New results do not “replace” our old ones, estrogen does not become good and bad and good again. Rather our newer, more refined studies serve to highlight the subtleties of the endocrine system, and we must constantly be aware that under certain conditions a therapy may be very beneficial while under other conditions, which may appear to vary modestly, that same therapy can be useless or even damaging.
And if you’re a lay person reading this, please talk to your physician. While I can’t dispense medical advice, I can help you find the starting points for an important conversation.
Oh, and one other thing… an increasingly large percentage of the population has been on birth control, which can also have long-term consequences and may interact with later HT. We may very well have to throw out everything we know about HT to accomodate our changing demographics. Ain’t hormones a blast?