Progesterone is a natural progestin which is synthesised in the ovaries, placenta, testes and the adrenal cortex. It is primarily used to treat amenorrhea, abnormal uterine bleeding and as a hormonal contraceptive. It can also be used to prevent early pregnancy failure in women undergoing an assisted reproductive technology and those with corpus lutetium insufficiency. In addition to these functions, its potential use for preterm delivery prophylaxis is being investigated. Some studies have revealed that progesterone can be effective in preventing preterm delivery in women with a higher risk of the condition. A study that was recently published supports the use of vaginal progesterone in women with a short cervix. Other forms of progesterone that can be acquired commercially include; oral capsules, intravaginal gels, intravaginal inserts, intramuscular injections and powder that can be used in extemporaneous formulations. A progesterone-releasing IUD- intrauterine device, that was inserted for a period of one year was previously available but currently, it is not present in the markets.
Progesterone was approved by the FDA in 1939. Micronised progesterone capsules for oral administration were later approved for secondary amenorrhea in May 1998, these capsules were later indicated and approved for the prevention of endometrial hyperplasia in postmenopausal women with an intact uterus and on an oestrogen replacement treatment. In May 1997, a progesterone vaginal gel was approved for progesterone replacement or supplementation as part of an assisted reproductive therapy for infertile women. A second intravaginal gel ‘proactive’ was released in the U.S in 2002. In June 2007, a vaginal insert known as Endometrin was also approved as part of an ART programme for infertile women.
The Mechanisms Of Action Of Progesterone.
Endogenous progesterone is responsible for two activities in the body. It induces the secretory activities of an oestrogen primed uterus as it prepares for the implantation of a fertilised egg in the uterus and it maintains pregnancy. Progesterone is secreted in the corpus lutetium as a response to the luteinizing hormones. This hormone increases the basal body temperature, inhibits pituitary secretion and it causes histological changes in vaginal tissues. It also stimulates the mammary alveolar gland tissues, inhibits uterine contractions during pregnancy and precipitates the withdrawal of bleeding when oestrogen is present. When progesterone is administered to women with an adequate production of oestrogen, it facilitates the transformation of the uterus from a proliferative phase to a secretory phase.
Progesterone has a primary contraceptive effect which involves suppressing the mid-cycle surge of the luteinizing hormones. However, its exact mechanisms of action are unknown. At the cellular levels, progestins diffuse freely into the target cells then bind to the cell receptors. Once they are bound to the receptors, they inhibit the release of gonadotropin hormone-releasing hormones from the hypothalamus and prevent preovulatory luteinizing hormone surge. This prevents the maturation of the follicles and ovulation. The binding sites where a majority of progestin cell receptors are found include; the mammary glands, the reproductive tract, the pituitary glands and the hypothalamus.
There is scientific reasoning that other additional mechanisms may be involved in facilitating progesterone’s contraceptive action. Progestin-only contraceptives have proven to prevent from 70-80% of ovulation circles while the clinical effectiveness of progesterone in contraception has been reported to be more than 96-98%. Some of its additional actions may include; increasing the viscosity of the cervical mucus which prevents the migration of sperms into the uterus and altering the tissues of the endometrium which can inhibit implantation of a foetus after fertilisation. Progesterone performs minimal androgenic and oestrogenic activities in the body.
Pharmacokinetics of progesterone.
Progesterone can be administered orally, intravaginally, intramuscularly or as a component of an intrauterine device. Vaginal suppositories are also manufactured but pharmacokinetic data is not available. Once in the body system, 96-99% of progesterone binds to cortisol binding globulin, albumin and sex hormone binding globulin. This hormone then undergoes hepatic metabolism into pregnanediol then it is conjugated with glucuronic acid. Once in the system, it has a half-life of 5-20 minutes then, more than 60% of its metabolites are excreted in the urine and about 10% via the bile and faeces.
After an oral administration, progesterone is absorbed naturally into the blood stream with peak serum concentrations occurring within 3 hours.
INDICATIONS OF PROGESTERONE.
Progesterone is indicated for progesterone replacement therapy and for progesterone supplementation in an assisted reproductive therapy (ART), this is principally for infertile women with a progesterone deficiency condition. It can also be used for the treatment of secondary amenorrhea, the reduction of some incidents related to endometrial hyperplasia, to treat abnormal uterine bleeding due to hormonal imbalances in the absence of some diseases like uterine cancer or fibroids and to minimise the risk of endometrial carcinoma in postmenopausal women receiving oestrogen replacement therapy.
CONTRAINDICATIONS OF PROGESTERONE AND SOME PRECAUTIONS WHEN USING IT.
Progesterone injection formulations should never be administered via intravenous administration. They are designed and specified for intramuscular use only.
You should never take this medication if you suffer from cardiac diseases or breast cancer. You should also avoid it if you have autoimmune diseases like blood clotting disorders, blood vessel diseases or systemic lupus erythematosus, vaginal cancer, if you have ever suffered from a stroke, dementia, liver and kidney diseases, high blood pressure, heart attacks, cases of high cholesterol, vaginal bleeding, if you smoke tobacco, and if you experience any hypersensitive and allergic reactions to progesterone or any of its products. You should also avoid this medication if you are pregnant or if you are trying to conceive. You should not drive or operate machinery until you are certain of the effects this medication has on you.
Progesterone is contraindicated in patients with hepatic dysfunctions and hepatic diseases since many hormonal contraceptives including progesterone are associated with hepatic tumours. Progesterone should be used cautiously in patients with hyperlipidemia because its effects have not been conclusively established.
Progesterone should be administered cautiously in patients with renal diseases, congestive heart failure, asthma and nephrotic syndrome. It can cause the retention of fluids in the body system which can worsen the symptoms of these conditions.
Its use should be monitored in patients with a migraine and a history of depression since it can worsen this too. Progesterone capsules are formulated with peanut oils so they should not be administered to patients who experience hypersensitive reactions to peanuts and its products.
An oestrogen/progesterone combination does not prevent memory loss in amenorrhoeic cases so a combination therapy is not advisable especially to women who are above 65 years.
Hormonal contraceptives have been associated with renal thrombosis so this medication should be stopped immediately in case patient experiences any visual disturbances.
Animal studies on the administration of progesterone during pregnancy do not indicate any evidence of foetal harm. But it should not be used if there is an ectopic pregnancy, during diagnostic tests for pregnancies and in cases of missed abortions. When delivered in high doses, progesterone acts as an infertility medication. It can chemically induce infertility in women so its use and administration should be effectively controlled.
Progesterone is compatible with breastfeeding. The presence of progestins in a mother’s milk is not expected to affect lactation, milk production or the infant, but you should be cautious because conclusive effects of these hormones on infants have not been established.
POSSIBLE INTERACTIONS OF PROGESTERONE.
To prevent any possible interactions of progesterone with any substances, You should inform your healthcare provider of any other drugs and medications that you are currently taking. You should also inform them if you smoke, use illegal drugs or take alcohol. Some substances that might interact with your medicine include; medications for sleep or seizures like carbamazepine, phenytoin, ketoconazole and rifampin.
Vaginal forms of progesterone should never be used with other intravaginal products since concurrent use may interfere with its absorption or release into the vagina tissues.
Drugs that function to reduce hepatic enzymes can increase the metabolism rates of various hormones including contraceptive hormones like progesterone. They should not be co-administered.
The concurrent use of progesterone and bromocriptine is not advised since bromocriptine is used to restore ovarian functions in amenorrhoeic while progesterone contradicts this. If they interact, one medication may counteract the functions of the other
Progesterone decreases the intake of iodide ions into the thyroid tissues. If you are on a sodium iodide treatment, you should limit or avoid any contact with progesterone.
This list may not contain all possible interactions for progesterone. Make sure you provide your physician with a complete list of all your current medications and treatments to be on the safe side.
SIDE EFFECTS AND ADVERSE REACTIONS RELATED TO PROGESTERONE MEDICATION.
The most common side effects of progesterone include menstrual flow changes, menstrual irregularities and amenorrhea. It can also lead to vomiting, weight gain, nausea, spotting, mastalgia or breast tenderness and mild headaches. Other reactions can include, an increase or decrease in libido, chloasma, melasma, cervicitis, breast discharge, vaginitis and an unusual weakness.
Patients with renal diseases or heart diseases can experience a worsening of their condition since progesterone can cause oedema and fluid retention in the system.
Hormonal contraceptives including progesterone can cause emotional lability. Its effects can be manifested as anxiety, mental depression, frustration anger and other emotional outbursts. Other events can include forgetfulness, aggression, headaches, dizziness and fatigue.
The insertion of an intrauterine device that contains progesterone into the vagina can possibly result to an infection. The infection has a higher risk of development within the first 20 days. It is however easily curable using any strong antibiotic.
Thromboembolic diseases are very common in hormonal contraceptive users compared to non-users.
The administration of progesterone using injections can often lead to injection site reactions which include pain, irritation and swelling.
Some adverse reactions affecting the GI that have been reported include; bloating, abdominal pains, constipation, diarrhoea, weight loss and appetite stimulation.
You should always call your doctor or health service provider as soon as you experience any signs of an adverse reaction after the administration of this medication.
HOW IS THIS MEDICATION BEST ADMINISTERED?
You should take this medication orally with water. Always take your doses at regular intervals as per the directions on the prescription label. If you happen to miss a dose, take it as soon as you can.
This medication should be stored at 59�F to 86�F (15�C to 30�C), away from heat, light and moisture. Keep all medicine out of the reach of children and throw away any unused medicine after the expiration date. Do not flush unused medicines or pour them down a sink.
Progesterone is commonly prescribed for, Prevention of overgrowth of the lining of the uterus in women who are taking oestrogens for menopausal symptoms and the treatment of secondary amenorrhea.
The dosage strengths of progesterone available:25, 50, 100, 150, 200 & 300 mg Capsule 25, 50, 100, 150 & 200 mg SR Capsule
The dosage form available for Progesterone is Capsules. Our pharmacy compounds all capsules according to the stringent USP 795 guidelines. Our quality-assurance process ensures consistency and uniformity in every compound we manufacture and dispense.