Progesterone is the active, natural progestin secreted by the ovary, mainly from the corpus luteum, from the placenta, and from the adrenal cortex. Progesterone released during the luteal phase of the normal female cycle leads to development of a secretary endometrium. Progesterone influences the endocervical glands, and progesterone is very important for the maintenance of pregnancy as progesterone suppresses menstruation and uterine contractility. Progesterone has application in the management of ovarian disorders, in dysfunctional irregular menstrual cycles, in dysmenorrhea, in premenstrual and post menopausal symptoms, especially in the latter where menopause is an endocrine deficiency state.
The medical and pharmaceutical prior arts administered progesterone as replacement therapy to provide progesterone for the physiological and therapeutic purposes indicated above, and more specifically for postmeno-pausal hormone replacement therapy. The medical and pharmaceutical prior arts administered progesterone for these therapies by injection with progesterone supplied in vegetable oil, progesterone in a suppository for vaginal or for rectal administration, progesterone in an intrauterine or vaginal device, and progesterone in a topical cream. The prior art dispensing of progesterone in oils, suppositories and creams lacked controlled delivery, and the prior art dispensing of progesterone in an intrauterine or vaginal device frequently lead to bleeding and infection of the uterus and the vagina. The prior art has not provided an acceptable oral means for administering progesterone at a controlled dose over time, even though patients are more comfortable taking compositions and dosage forms by mouth. The properties of progesterone are reported in The Pharmacological Basis of Therapeutics, by Gilman and Rall, 8th ed, pp 1384-1412 (1990), published by Pergamon Press, Inc.