Estradiol benzoate is the synthetic benzoate ester of estradiol, a steroid sex hormone vital to the maintenance of fertility and secondary sexual characteristics in females. As the primary, most potent estrogen hormone produced by the ovaries, estradiol binds to and activates specific nuclear receptors. This agent exhibits mild anabolic and metabolic properties, and increases blood coagulability. Although estradiol benzoate is not approved by the FDA for use in humans in the United States, it is approved for veterinary use as a subdermal implant both alone (CELERIN®) and in combination with the anabolic steroid trenbolone acetate (SYNOVEX® Plus).

Progesterone is indicated in amenorrhea and abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, such as submucous fibroids of uterine cancer. Progesterone, converted from pregnenolone, also serves as an intermediate in the biosynthesis of gonadal steroid hormones and adrenal corticosteroids. Progesterone is a naturally occurring steroid that is secreted by the ovary, placenta, and adrenal gland. In the presence of adequate estrogen, progesterone transforms a proliferative endometrium into a secretory endometrium. Progesterone is necessary to increase endometrial receptivity for implantation of an embryo. Once an embryo is implanted, progesterone acts to maintain a pregnancy. Progesterone shares the pharmacological actions of the progestins. Progesterone binds to the progesterone and estrogen receptors. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Once bound to the receptor, progesterone will slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH (luteinizing hormone) surge. In women who have adequate endogenous estrogen, progesterone transforms a proliferative endometrium into a secretory one. Progesterone is metabolized primarily by the liver largely to pregnanediols and pregnanolones. Pregnanediols and pregnanolones are conjugated in the liver to glucuronide and sulfate metabolites. Progesterone metabolites that are excreted in the bile may be deconjugated and may be further metabolized in the gut via reduction, dehydroxylation, and epimerization. Common progesterone side effects may include: drowsiness, dizziness; breast pain; mood changes; headache; constipation, diarrhea, heartburn; bloating, swelling in your hands or feet; joint pain; hot flashes; or vaginal discharge.

Vilaprisan, a small molecule progesterone receptor antagonist is being developed by Bayer HealthCare Pharmaceuticals (formerly Bayer Schering Pharma) for the treatment of endometriosis and uterine leiomyoma. Hormonal imbalance observed in women with endometriosis is a potential target for treating endometriosis. Vilaprisan is a highly selective steroidal progesterone receptor modulator (SPRM). It is a partial agonist of progesterone receptor, which means that the drug activates progesterone receptors to a certain degree upon binding. This triggers a cascade of biochemical reactions that result in the suppression of prostaglandin production. This, in turn, relieves symptoms such as pain and bleeding. Modulating progesterone by taking vilaprisan might help in treating endometriosis over the long term. Phase I and II studies give encouraging results on the efficacy of vilaprisan at different doses. Like other SPRMs, vilaprisan induces benign changes of endometrium (PR modulator-associated endometrial changes, PAECs). These disappear as treatment is discontinued. Unlike GnRHa treatment, neither UPA nor vilaprisan induce hypoestrogenism and associated symptoms. Phase III studies are ongoing to confirm efficacy and safety of vilaprisan in long-term treatment of symptomatic fibroids.

Telapristone is an orally available 21-substituted-19-nor-progestin and selective progesterone receptor modulator (SPRM), with potential anti-progesterone and antineoplastic activities. Its acetate form, the telapristone Acetate is a clinically used and a studied drug.

Toripristone has a high inhibiting activity against the cortisol receptors. Toripristone enhanced the antibacterial activities of the sparfloxacin in combination with ethambutol in the treatment of M. avium complex infections. Also, toripristone is a glucocorticoid type II receptor and progesterone receptor antagonist. Toripristone treatment was estimated to selectively occupy approximately 50% of glucocorticoid receptors in rat brain.

Aglepristone (RU 46534) is a competitive progesterone antagonist; it binds to progesterone receptors (PRs) without inducing the molecular cascade associated with progesterone. Its affinity to PRs is higher than progesterone (3.12, 3.8, and 9.26 times greater in the bitch, doe rabbit,and queen, respectively). Aglepristone can therefore beused in various progesterone-dependent physiological orpathologic conditions, with the aim of blocking the action of progesterone. Aglepristone has proven to be an effective and safe means of inducing pregnancy termination or parturition in a large number of domestic species. In domestic species, aglepristone is routinely used for the treatment of pyometra and feline mammary fibroadenomatous hyperplasia, both of which are progesterone dependent. Aglepristone is marketed under the brand name Alizin used as the treatment option for unwanted mating and pregnancy in dogs

Lonaprisan is an orally bioavailable pentafluoroethyl derivative of a mifepristone-related steroid with antiprogestagenic activity. Lonaprisan is a pure, highly receptor-selective progesterone receptor (PR) antagonist (both PR isoforms PR-A and PR-B); binding of this agent to PRs inhibits PR activation and the associated proliferative effects. Lonaprisan showed limited efficacy as second-line endocrine therapy in postmenopausal women with PR-positive metastatic breast cancer. Lonaprisan had been in phase II clinical trials by Bayer for the treatment of breast cancer and dysmenorrhea. However, this research has been discontinued.

Lilopristone (ZK 98.734) has a high affinity for progesterone receptors. The progesterone antagonistic effects of ZK 98.734 could be a result of the decrease in progesterone synthesis by the corpus luteum and/or placenta in addition to the interference with the progesterone binding to its cellular receptors in the target organ. ZK 98.734 has potential for fertility regulation. It is a very potent abortifacient in the common marmosets. Lilopristone could significantly suppress the proliferation of ectopic stromal cells in a time- and dose-dependent manner in vitro. The action mechanisms may be associated with the suppression of expression of NF-kappaB P65 mRNA and NF-kappaB P65.

Asoprisnil (J867) is a novel selective steroid receptor modulator that shows unique pharmacodynamic effects in animal models and humans. Asoprisnil, its major metabolite J912, and other structurally related compounds represent a new class of progesterone receptor (PR) ligands that exhibit partial agonist and antagonist activities in vivo. Asoprisnil demonstrates a high degree of receptor and tissue selectivity, with a high-binding affinity for PR, moderate affinity for glucocorticoid receptor (GR), low affinity for androgen receptor (AR), and no binding affinity for estrogen or mineralocorticoid receptors. This compound was recently in clinical trials for the treatment of uterine fibroids and endometriosis, but those studies were discontinued.

Epostane (WIN-32729) a pure competitive inhibitor of 3-beta-hydroxysteroid dehydrogenase. Epostane blocks progesterone synthesis during the luteal phase and in pregnancy in women and has strong anti-steroidogenic effect in endocrine tissues. Epostane is an abortifacient agent in early human pregnancy. It inhibits ovarian follicular steroidogenesis and ovulation.