When estrogen alone is administered, it stimulates the uterine lining called the “endometrium” to transform into its proliferative phase. During the menstrual years, this phase lasts between 6-20 days with the average being 14 days. After the ooycte is released from the ovarian follicle, known as ovulation, the follicle space in the ovary transforms into the corpus luteum that secretes progesterone (P4). The progesterone stimulates the glands located in the endometrium to secrete their nourishing substances, known as the secretory phase of the endometrium. These nutrients help sustain a fertilized egg.  If no fertilized egg arrives inside the uterus then the corpus luteum shrivels up and dies after only 12 days. Falling estrogen and progesterone levels trigger the tiny arteries within the endometrium to constrict depriving the endometrium of nutrients and oxygen. This causes the endometrium to sluff or shed as menstrual flow leaving only the bottom 1/3 to form a new lining for the next cycle. This keeps the uterine lining thin and prevents it from getting excess estrogen stimulation. If the endometrium sees continuos estrogen stimulation, the endometrium can transform into hyperplasia or pre-cancer. With time the hyperplasia can transform into uterine cancer, specifically known as endometrial cancer. This is a slow process and takes many months to several years of unopposed estrogen to cause the transformation to cancer. The point here is that the uterus must be exposed to adequate progestin each mouth to prevent hyperplasia from developing. That was the hormone lesson learned in the 1960’s. When hormone therapy for menopausal symptoms first started, estrogen was administered alone which caused a big spike in uterine cancer. When progestin was added back, that risk totally resolved meaning it returned to baseline. What does this mean to you? If you have your uterus in place and not menstruating and you are given estrogen in doses known to stimulate the uterus or even suspected that it might stimulate the uterus, then you need to be on a progestin. To hedge on the safe side, and since progestins do not have serious side effects, for women with their uterus in place, FGI protocols include a progestin for those that are post-menopause and have their uterus. Not all progestins are equally tolerated. Common progestin side effects include fluid retention, bloating, appetite stimulation and mood irritability. Based on my clinical observations, these side effects occur more commonly with the bio-identical progestin known as progesterone (P4) rather than the synthetic progestins such as norethindrone acetate (NE) or megace. Many women who are sensitive to progesterone, get PMS symptoms during the secretory phase of their menstrual cycle when the ovaries are secreting progesterone. Perhaps for that reason there is not a single OCP on the market that contains P4, or natural progesterone. Some of these women have their PMS return when they are started on HRT. This can usually be fixed by using one of the other progestins rather than P4.