Women with POI are missing the main hormone messenger estradiol, which has the main function of maturing and then maintaining the reproductive system. During the menstrual cycle, increased estradiol levels permit the maturation and release of the egg, as well as the thickening of the uterus lining to allow a fertilized egg to implant.
P-HRT restores the natural levels of estradiol using the exact same hormone — that is, estradiol itself. The term “physiologic” means the estradiol is administered directly into your bloodstream, typically via a skin patch or vaginal ring, rather than through the mouth and past the liver. Estrogens taken by mouth (as in traditional HRT) expose the liver to extremely high levels of estrogen and change normal liver function in adverse ways. In short, P-HRT averts this risk. Here is the good news based on the best evidence:
- Blood clots: With P-HRT the estradiol is given by skin patch or vaginal ring, which does not increase the risk of blood clots. In contrast, taking estrogens by mouth in the form of a pill increases the risk for developing blood clots, which can be fatal if they travel to the lungs. The risk of this complication is greater for people who smoke or are obese and take traditional HRT.
- Breast cancer: For women with POI, the P-HRT is not expected to increase the risk of breast cancer above normal. POI is unique in that young women are replacing the hormones their ovaries would normally be providing, which is dramatically different than older women who have normal menopause and are beyond the age of their body making the estradiol amounts found in younger women. In short, women with POI take physiologic “hormone replacement” when they use the estradiol patch or vaginal ring. Menopausal women who take estrogen and progestin replacement by mouth are not taking “hormone replacement;” indeed, these women are extending estrogen exposure beyond what takes place naturally. As such, estrogen and progestin replacement taken by mouth in menopausal women has been associated with a higher risk of breast cancer due to the longer exposure to estrogen.
- Uterine or Endometrial cancer: When taken alone, estradiol increases the risk for uterine cancer, which is why a progestogen is recommended in addition to estradiol replacement in POI. However, for women who have had their uterus removed, it is not necessary to take a progestogen.