Analysis of Depo-Provera - Assignment Example

Compare one type of contraception known as Depo-Provera and the biological mechanisms that it uses to different types of contraception and the mechanisms that they use Introduction Depo-Provera is the trade name for Depot medroxyprogesterone acetate (DMPA) (Pfizer company). It is an aqueous suspension for depot injection of the pregnane 17a-hydroxyprogesterone-derivative progestin medroxyprogesterone acetate. It is a long acting hormonal contraceptive and infact the first of its kind, which is usually given as an injection once every three months (Depo- vera, College statement). Medroxyprogesterone acetate is a white-to-off white odorless crystalline powder. It is stable in air and melts at 200 deg. C to 210 deg. C. It is insoluble in water and soluble in organic solvents. Each ml of Depo-Provera contains 150 mg of medroxyprogesterone acetate. The chemical name of medroxyprogesterone acetate is pregn-4-ene-3, 20-dione, 17- (acetyyloxy)-6- methyl-, (6 alpha)-. Pharmacokinetics The serum half-life of the drug is 50 days. Following a single dose of 150 mg given intramuscularly, the peak plasma levels of 1-7 ng/ml are attained at 3 weeks. After this peak, the levels gradually decrease between 120-200 days following injection. The effect of liver or renal diseases on the pharmacokinetics of the drug is unknown. It decreases plasma levels of cortisol, estrogen, pregnendiol, progesterone and testesterone. It also decreases levels of gonadotrophins and sex-hormone binding globulin (Drug Label, Depo-Provera). Indications The only indication for the use of this drug is contraception. It is an effective contraceptive with less than 1 pregnancy per 100 users per year (Population Reports, BNET Research). It can also be used in the treatment of endometriosis, abnormal menstrual bleeding or amenorrhea (Chrousos, p.663). Mode of action Like other progestins, medroxyprogesterone acetate enters the cell and binds to progesterone receptors that are distributed between the nucleus and the cytoplasm. The ligand-receptor complex then binds to a progesterone response element to activate gene transcription (Chrousos, p.663). It prevents follicular maturation and ovulation and causes endometrial thinning. These actions produce the contraceptive effect (Drug Label, Depo-Provera). Contraindications DMPA is contraindicated in pregnant women. This is because there is some evidence suggesting the development of genital abnormalities in fetuses exposed to this drug in the first trimester. Also, studies have shown that the babies may have low birth weight which can increase the risk of neonatal complications. Though the metabolites of DMPA are secreted in breast milk, no apparent hazard to the feeding baby is known. Other contraindications include vaginal bleeding of unknown cause, severe liver dysfunction and known hypersensitivity to medroxyprogesterone acetate or any of the other components of the injection and breast cancer (Drug Label, Depo-Provera) Special precautions The drug must be used with caution in those with problems of fluid retention like congestive cardiac failure because the drug itself may cause fluid retention. The drug decreases glucose tolerance and hence must be used with caution in diabetes mellitus. The medication must not be repeated in case of occurrence of migraine, diplopia, sudden loss of vision, papilledema or thromboyic complications (Drug Label, Depo-Provera). Side effects The widely studied side effect of medroxyprogesterone acetate is decreased bone mineral density (BMD). This is due to decreased estrogen levels. The loss increases as the duration of treatment increases. The effects are seen more in adolescents and young women. The drug is not recommended for use beyond 2 years in view of this side effect. During long term treatments, the BMD should be regularly evaluated and the patient should receive adequate calcium and Vit. D supplements. Other side effects include vaginal bleeding, fluid retention, depression symptoms, decreased glucose tolerance, disruption of menstrual bleeding patterns, weight gain (Drug Label, Depo-Provera), head ache, stomach cramps, dizziness, nausea, bloating, hot flashes, acne, change in appetite, sweating, weight gain, change in sexual desire or pain and irritation at the injection site (Depo-Provera Contraceptive, MedicineNet.com). Drug interactions Concomitant administration of aminoglutethimide depresses serum concentrations of medroxyprogesterone acetate (Drug Label, Depo-Provera). Dosage It is given intramuscularly as a single dose every 3 months. Storage The injection must be stored at room temperature between 59 and 86 degrees F (between 15 and 30 degrees C) away from heat and light. It should not be stored in the bathroom (Depo-Provera Contraceptive, MedicineNet.com). Important non-contraceptive benefits DMPA reduces menstrual bleeding and may help to prevent anemia. In those with sickle cell anemia, it may reduce the frequency of sickle-cell crises. There is lesser risk of ectopic pregnancy and endometrial cancer. Who can administer the drug? The drug is available only on prescription. However, health professionals who know to give injections can administer the drug. The drug must be taken after consultation with a physician who examines the indications and contraindications for the medication. Special advice This mode of contraception does not decrease the risk of sexually transmitted diseases and HIV infection. Hence the couple must use condoms also. Mode of administration Medroxyprogesterone acetate is active by the parental and oral routes of administration. However, Depo-Provera is the injectable form, given intramuscularly. Drug approval The drug has been approved by drug regulatory agencies over 100 countries in the world. The United States Food and Drug Administration approved DMPA for contraception in October 1992 (Population Reports, BNET Research). Cost The cost of the drug is much more when compared to oral contraceptive pills. In a study by Marguilies and Miller (2001), the cost of medroxyprogesterone acetate is $4.75 for 28 days and that for the average pill package is purchased for $1.35, which means the cost is 4 times greater for the injection contraceptive user than for the oral contraceptive user. Other contraceptive measures and their mechanisms 1. Periodic abstinence: This can be achieved by coitus interruptus and natural family planning. Coitus interruptus involves withdrawal of the entire penis from the vagina before ejaculation and fertilization is prevented by lack of contact between spermatozoa and the ovum. In natural family planning, there is periodic abstinence, with couples attempting to avoid intercourse during a womans fertile period. Lactational amenorrhea also causes contraception because elevated prolactin levels and reduction of gonadotropin-releasing hormone from the hypothalamus during lactation suppress ovulation (Samra, eMedicine). 2. Mechanical barriers: Male condoms, female condoms, diaphragms, cervical cap and spermicidal agents are the means of mechanical barriers. The male condom consists of a thin sheath placed over the glans and the shaft of the penis that is applied before any vaginal insertion. The seminal fluid collects in the condom, thus preventing contact between ova and sperm. The female condom is a polyurethane sheath. It acts as a barrier to the passage of semen into the vagina. The diaphragm is a shallow latex cup that will be placed in the vagina. It prevents pregnancy by acting as a barrier to the passage of semen into the cervix. Cervical cap is a cup-shaped latex device that fits over the base of the cervix. The cup is filled with a spermicidal jelly. This acts both as a mechanical barrier and a spermicidal agent. Vaginal spermicides consist of a base combined with either nonoxynol-9 or octoxynol. The base is a surfactant that destroys the sperm cell membrane. The base can be vaginal foams, suppositories, jellies, films, foaming tablets or creams which is inserted into the vagina prior to each coital act (Samra, eMedicine). 3. Hormonal contraceptives: The hormonal contraceptives are in the form of implants, injections, progestin only oral contraceptives, combination oral contraceptives, ninety-one day combination oral contraceptives, combination patch contraceptives and contraceptive vaginal ring. The implants used are evonorgestrel implants. They act by suppression of the LH surge, suppression of ovulation, development of viscous and scant cervical mucus to deter sperm penetration, and prevention of endometrial growth and development. Other than DMPA, other injectable contraceptives are NET EN (norethindrone enanthate, or Noristerat [R]), effective for 2 months, and Cyclofem [TM] and Mesigyna [R], both effective for 1 month. DMPA and NET EN are progestin-only injectables, while 1-month injectables contain both progestin and estrogen (Population Reports, BNET Research). Progestin only oral contraceptives act by suppression of ovulation, dampening effect on the midcycle peaks of LH and FSH, increase in cervical mucus viscosity, causing atrophic endometrium not suitable for ovum implantation and by reducing cilia motility in the fallopian tube, thus slowing the rate of ovum transport. Combination oral contraceptives contain both estrogen and progesterone. These act by prevention of ovulation by synergistic effect that greatly increases their antigonadotropic and ovulation-inhibitory effects. Ninety-one day combination oral contraceptive, called seasonale contains a regimen in which tablets containing the active hormones are taken for 84 days, followed by 7 days of placebo tablets. The active ingredients are progestin and estrogen. It acts by inhibition of ovulation. Combination patch contraceptive consists of a transdermal patch that release estrogen and progesterone directly into the skin. Contraceptive vaginal ring consist of steroid mixed uniformly through a polysiloxane matrix (Samra, eMedicine). 4. Intra-uterine devices The mainly used intra-uterine device is T-shaped progesterone-releasing IUD Progestasert. It is placed in the uterine cavity. It causes cervical mucus to be thicker in consistency, thereby altering sperm migration. It also causes endometrial suppression (Samra, eMedicine). 5. Sterilization This is a permanent method of contraception. In female sterilization, the fallopian tubes are interrupted by occlusion with rings, clips, bands, electrocoagulation or suture ligation. In male sterilization, vasectomy is done. Vasectomy prevents the passage of sperm into seminal fluid by blocking the vas deferens (Samra, eMedicine). Works Cited page Chrousos, G.P. “The Gonadal Hormones and Inhibitors.” Basic and Clinical Pharmacology. Boston: Mc GrawHill Lange, 2007, p.663-667. “Depot Medroxyprogesterone Acetate (Depo-Provera).” College Statement. The Royal Australian and New Zealand College of Obstetricians and Gynaecologists. 12 Dec 2007 “Depo-Provera Contraceptive.” MedicineNet.com. 2005. 12 Dec 2007 Drug Label. “Depo-Provera.” Pfizer Pharmaceutical Company. Margulies, Rebecca, Miller, Leslie. “Increased depot medroxyprogesterone acetate use increases family planning program pharmaceutical supply costs.” Contraception 63.3 (2001): 147-149. Population Reports. “DMPA at a glance - depot medroxyprogesterone acetate, also known as Depo-Provera.” BNET Research . 1995. 12 Dec 2007 Samra, Omnia. “Contraception.” 2006. eMedicine from WebMD. 12 Dec 2007 Read More