Progesterone is the active, natural progestin secreted by the ovary, mainly from the corpus luteum, from the placenta, and from the adrenal cortex. Progesterone is a natural reproductive hormone that targets the breast, uterus, ovaries, brain, bone, blood vessels, immune system, etc. 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 is responsible for the progestational changes of the endometrium and the cyclic changes of cells and tissues in the cervix and the vagina. For example, progesterone makes the cervical mucus thick, tenacious and cellular. It is believed that thickened mucus impedes spermatozoal transport. During a woman's reproductive life, a delicate and complex interplay of hormones are timed and controlled by the hypothalamus. The hormones that participate in the feedback system regulating the menstrual cycle include estrogens and progesterone, the pituitary gonadotropins FSH (follicle stimulating hormone) and LH (luteinizing hormone), and gonadotropin-releasing hormone (GnRH) from the hypothalamus. Progesterone is a naturally occurring steroid which is the main steroid secreted by women during their reproductive years. This steroid has been studied extensively and has been found to be a major precursor in the biosynthesis of most other steroids, particularly glucocorticoids, androgens and estrogens. The sex steroid hormone progesterone is involved in preparing the uterus for implantation of the fertilized ovum. Progestins have proliferative and differentiating effects on mammary epithelium.
A progestin is a compound capable, by definition, of maintaining gestation and of promoting implantation of the egg. Progestins include the natural progestin, progesterone, as well as the synthetic progestins, such as medroxyprogesterone acetate (MPA). Progestins have been used pharmaceutically in the treatment of a number of clinical disorders such as luteal phase deficiency, dysfunctional uterine bleeding, endometriosis, endometrial carcinoma, benign breast disease, pre-eclampsia, and assisting in vitro fertilization, preventing early abortion and reducing the occurrence of endometrial hyperplasia in estrogen replacement therapy (ERT). It has been demonstrated that progestins prevent the development of hyperplasia and endometrial cancer, sequential or combined therapy with estrogens and progestins is advised in menopausal women who have not undergone a hysterectomy. Progesterone, synthetic progestins, and antiprogestins all initially work through the same molecular pathway. They enter target cells passively, and pass into the nucleus where they bind to progesterone receptors (PRs). Ligand binding activates the PR proteins, which then dimerize, bind to DNA at the promoters of progesterone target genes, and either up- or down-regulate transcription of these genes. Progesterone plays a major role in reproductive health and functioning. The actions of progesterone as well as progesterone antagonists are mediated by the progesterone receptor (PR). Progesterone is essential for lobuloalveolar development and preparation for lactation. When ovulation is established progesterone, produced by the corpus luteum, stimulates growth of the lobuloalveolar structures and during pregnancy promotes branching of the ductal system and differentiation of alveolar cells into secretory cells ready for milk production. Progesterone also stimulates the growth of the uterus and a number of specific changes in the endometrium and myometrium. It is essential for the development of decidual tissue and the differentiation of luminal and glandular epithelial tissue. Progesterone also plays several roles in gestation, including breast enlargement, inhibition of uterine contractility, maintenance of gestation, immunological protection of the embryo, and inhibition of prostaglandin synthesis.
The use of substituted steroids for a number of therapeutic purposes, e.g., in the control of conception in female mammals in the regulation of the menstrual cycle, in conjunction with chemotherapy, and for a number of other purposes, has been known for some time. 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. Hormone replacement therapy is used to improve the quality of life of women during this natural ageing process to alleviate symptoms associated with this time of transition and to reduce the likelihood or slow the progression of disorders and diseases associated with reduced estrogen activity. The use of hormone replacement therapy is well established to date for relieving menopausal symptoms. Among progestins suitable for hormone replacement therapy, micronized progesterone is preferably used due to its lack of androgenic effect and its metabolic innocuity. The most common progestational agents used are the synthetic progestins, which are accompanied by undesirable side effects such as depression and water retention. Additionally, many of the synthetic progestins derived from 19-nor-testosterone reverse the positive effects of estrogen on lipoprotein (HDL) levels. Natural progesterone does not cause water retention, is rarely associated with depression and has no adverse effects upon lipid levels. |
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