Compounded Immediate Release: 10 mg, 25 mg, 50 mg, 75 mg, 125 mg, 150 mg, 250 mg, 300 mg Compounded Slow Release: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 125 mg, 150 mg, 175 mg, 200 mg, 250 mg, 300 mg

Progesterone is a naturally occurring progestin. In the body, it is synthesized in the ovaries, testes, placenta, and adrenal cortex. Progesterone is primarily used to treat amenorrhea, abnormal uterine bleeding, or as a contraceptive. Progesterone is also used to prevent early pregnancy failure in women with corpus luteum insufficiency, including women undergoing assisted reproductive technology (ART). Additionally, the use of progesterone for preterm delivery prophylaxis is being investigated. Preliminary data indicate that progesterone may be effective in preventing preterm delivery in high-risk women, especially those with a history of preterm delivery;1 however, the optimal dosage and route have not been determined. The American College of Obstetricians and Gynecologists (ACOG) Committee recommends that if progesterone is to be used for the prevention of preterm delivery, it should only be used in women with a history of spontaneous birth at < 37 weeks gestation, until more data supporting its use in other high-risk women are available. A study in support of the use of vaginal progesterone in women with a short cervix has been published. Progesterone is available commercially as an intramuscular injection, an intravaginal gel, an intravaginal insert, oral capsules, or a powder for use in extemporaneous preparations (e.g., vaginal suppositories). A progesterone-releasing IUD (Progestasert®) that was inserted once yearly has been discontinued. Progesterone was approved by the FDA in 1939. In May 1998, micronized progesterone capsules for oral administration were approved for secondary amenorrhea; they received a second indication in December 1998 for the prevention of endometrial hyperplasia in postmenopausal women with an intact uterus taking estrogen replacement therapy. In May 1997, a progesterone vaginal gel (Crinone®) was approved for progesterone supplementation or replacement as part of an Assisted Reproductive Technology (ART) program for infertile women; a second intravaginal gel, Prochieve™, was released to the US market in 2002. A vaginal insert, Endometrin®, for progesterone supplementation as part of an ART program in infertile women was approved in June 2007

Endogenous progesterone is responsible for inducing secretory activity in the endometrium of the estrogen-primed uterus in preparation for the implantation of a fertilized egg and for the maintenance of pregnancy. It is secreted from the corpus luteum in response to luteinizing hormone. The hormone increases basal body temperature, causes histologic changes in vaginal tissues, inhibits uterine contractions, inhibits pituitary secretion, stimulates mammary alveolar gland tissues, and precipitated withdrawal bleeding in the presence of estrogen. The administration of progesterone to women with adequate estrogen production transforms the uterus from a proliferative to a secretory phase. The primary contraceptive effect of exogenous progestins involves the suppression of the midcycle surge of LH. The exact mechanism of action, however, is unknown. At the cellular level, progestins diffuse freely into target cells and bind to the progesterone receptor. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Once bound to the receptor, progestins slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the preovulatory LH surge, thereby preventing follicular maturation and ovulation. Overall, progestin-only contraceptives prevent ovulation in 70—80% of cycles, however, the clinical effectiveness ranges 96—98%. This suggests that additional mechanisms may be involved. Other actions of progestins include alterations in the endometrium that can impair implantation and an increase in cervical mucus viscosity which inhibits sperm migration into the uterus. Progesterone administered via IUD suppresses proliferation of endometrial tissue. Following removal of the IUD, the endometrium rapidly returns to a normal cyclic pattern and can support pregnancy. Progesterone has minimal estrogenic and androgenic activity.

Do not take this medicine if you have breast cancer, cardiac disease or dementia. Your health care provider needs to know if you have any of these conditions: autoimmune disease like systemic lupus erythematosus (SLE); blood vessel disease, blood clotting disorder, or suffered a stroke; breast, cervical or vaginal cancer; dementia; diabetes; kidney or liver disease; heart disease, high blood pressure or recent heart attack; high blood lipids or cholesterol; hysterectomy; tobacco smoker; vaginal bleeding; an unusual or allergic reaction to progesterone or other products; pregnant or trying to get pregnant; breast-feeding. This medicine can cause swelling, tenderness, or bleeding of the gums. Do not drive, use machinery, or do anything that needs mental alertness until you know how this drug affects you. Progesterone is contraindicated in undiagnosed abnormal vaginal bleeding orincomplete abortion. Hormones can cause irregular menstrual bleeding in most women. In general, these irregularities diminish with continuing use. Women should be counseled regarding irregular menstrual bleeding. Progesterone is contraindicated in patients with pre-existing breast cancer or cancer of reproductive organs, such as cervical cancer, uterine cancer, or vaginal cancer, except as palliative therapy in selected patients. Although progestins reduce the risk of endometrial cancer in patients receiving estrogen replacement therapy, it is unclear whether progestins added to estrogen therapy reduce the risk of breast cancer in postmenopausal women. Progesterone should be used cautiously in patients with hyperlipidemia. Although hyperlipidemia is associated with estrogen-progestin combinations, the effects of progestin-only oral contraceptives on serum lipids have not been studied. Serum lipoproteins (HDL and LDL) should be monitored during therapy with progesterone

Progesterone capsules are classified in FDA pregnancy category B. Animal studies involving oral or intravaginal or in utero administration of progesterone have, in general, not indicated evidence of fetal harm. In general, several studies of women exposed to progesterone during pregnancy for luteal support have not demonstrated a significant increase in fetal malformations. A single case of cleft palate has been reported in an infant exposed to micronized progesterone in utero. Rare cases of fetal death have been reported in women administered micronized progesterone in early pregnancy, but causality has not been established. Only select products are specifically labeled for use to provide luteal support during pregnancy.56 Crinone progesterone vaginal gel may be used to support early pregnancy as part of an Assisted Reproductive Technology (ART) program; if pregnancy occurs, the gel is typically continued for 10—12 weeks until placental production of progesterone is adequate to support the pregnancy. Similarly, Endometrin vaginal inserts are used for up to 10 weeks in ART. Progesterone should only be used during early pregnancy under the observation of an ART specialist; data suggest that progesterone may be effective in preventing preterm delivery, especially in high-risk populations.31 The American College of Obstetricians and Gynecologists (ACOG) Committee recommends that if progesterone is to be used, it should only be used in women with a history of spontaneous birth at < 37 weeks gestation; in addition, the ideal formulation or whether it should be used in other high-risk women is not yet known.2 Progesterone should not be used if there is ectopic pregnancy, during cases of missed abortion, or during diagnostic tests for pregnancy. In high doses, injectable progesterone is an anti-fertility drug and may chemically induce female infertility.

In general, the American Academy of Pediatrics considers progesterone to be compatible with breast-feeding.7 Detectable amounts of progestins have been identified in the milk of nursing mothers; in general the presence of progestins in the milk are not expected to have adverse effects on lactation production. However, the effects of progestins present in breast milk on the nursing infant have not been determined. The administration of any medication to nursing mothers should take into account the benefit of the drug to the mother and the potential for risk to the breast-fed infant.

The most common adverse reactions occurring during therapy with progesterone include menstrual irregularity, menstrual flow changes, and dysmenorrhea or amenorrhea. These effects may be indistinguishable from pregnancy. Progesterone also causes spotting, breakthrough bleeding, weight gain, nausea, vomiting, breast tenderness or mastalgia, and mild headache. These adverse effects occur less frequently with progestin-only OCs compared to combination OCs. Other reported adverse reactions during therapy include melasma, chloasma, libido decrease, libido increase, breast discharge, cervicitis, galactorrhea, hirsutism, leukorrhea, unusual weakness, and vaginitis. Post-marketing experiences with oral progesterone include endometrial carcinoma, hypospadia, intra-uterine death, menorrhagia, menstrual disorder, metorrhagia, ovarian cyst, and spontaneous fetal abortion. Additional adverse reactions associated with the intravaginal gel include breast enlargement, dyspareunia, nocturia, perineal pain, dysmenorrhea, premenstrual tension, vaginal dryness, and vaginal discharge. Adverse reactions associated with vaginal inserts include vaginal irritation, vaginal itching, vaginal burning, and vaginal pain/discomfort. Fluid retention and/or edema may occur in patients receiving progesterone. Patients with heart failure and/or renal disease may experience an exacerbation of their condition. Post-marketing reports of adverse reactions with oral progesterone include facial edema, circulatory collapse, congenital heart disease, hypertension, hypotension, and sinus tachycardia. Adverse reactions reported with progesterone use include abnormal gait, arthralgia, choking (with oral formulations), cleft lip, cleft palate, tinnitus, vertigo, cystitis, dysuria, increased urinary frequency, leg pain, musculoskeletal pain, flu-like symptoms, xerophthalmia, benign cyst, purpura, anemia, infection, pharyngitis, sinusitis, urinary tract infection, and conjunctivitis.

Store this medication at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond use date. Do not flush unused medications or pour down a sink or drain.