Mirena and Estrogen for Control of Perimenopause Symptoms and Ovulation Suppression
Status:
Completed
Trial end date:
2014-06-01
Target enrollment:
Participant gender:
Summary
Hormonal treatment of perimenopausal women has frequently utilized oral contraceptive pills
(OCPs). Because of their ability to suppress ovulation and establish cycle control, OCPs have
become a popular option, and one that is FDA approved for use until menopause. However, use
of OCPs in women in their 40's and 50's carries significant cardiovascular risks. Venous
thromboembolism risk is 3-6 fold greater in OCP users, and the risk of myocardial infarction
(MI) is approximately doubled in OCP users over the age of 40. This occurs at an age where
the background population risk of MI begins to increase, such that the absolute number of
cases rises substantially. Women with additional risk factors for cardiovascular disease have
a much greater risk for MI (6-40-fold) in association with OCPs. There are also large
subgroups of midlife women who are not candidates for OCP use, such a smokers and
migraineurs. Moreover, the trend towards lower estrogen dosing with OCPs containing 20
micrograms of ethinyl estradiol has not led to a detectable decrease in thromboembolic risk.
Because of their increased potential risks, it is appropriate to seek alternatives to OCPs
and to explore lower doses of hormones to relieve perimenopausal symptoms that occur prior to
a woman's final menses. Recent evidence indicates that the hypothalamic-pituitary axis of
reproductively aging women is more susceptible to suppression by sex steroids that previously
believed. It is possible that hormone doses as low as 50 micrograms of transdermal estradiol
(TDE) can suppress the hypothalamic-pituitary axis of midlife women. It is also tempting to
speculate that the low but measurable circulating doses of levonorgestrel that are present
when a woman uses the Mirena intrauterine system (IUS) can contribute to or even
independently suppress the hypothalamic-pituitary axis, and reduce the hormonal fluctuations
that result in worsening of perimenopausal symptoms. The combination of low dose TDE plus
Mirena may therefore confer superior symptom control as well as contraceptive effectiveness,
at far less risk.