Depo-Provera Contraceptive Injection is the brand name for a 150 mg aqueous suspension of medroxyprogesterone acetate for depot intramuscular injection every 3 months (12–13 weeks) manufactured by Pfizer.
depo-subQ provera 104 is the brand name for a 104 mg aqueous suspension of medroxyprogesterone acetate for depot subcutaneous injection every 3 months (12–14 weeks) manufactured by Pfizer.
The mechanism of action of progestogen-only contraceptives depends on the progestogen activity and dose. High-dose progestogen-only contraceptives, such as injectable DMPA, inhibit follicular development and prevent ovulation as their primary mechanism of action.
The progestogen decreases the pulse frequency of gonadotropin-releasing hormone (GnRH) release by the hypothalamus, which decreases the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by the anterior pituitary. Decreased levels of FSH inhibit follicular development, preventing an increase in estradiol levels. Progestogen negative feedback and the lack of estrogen positive feedback on LH release prevent a LH surge. Inhibition of follicular development and the absence of a LH surge prevent ovulation.
Inhibition of ovarian function during DMPA use causes the endometrium to become thin and atrophic. These changes in the endometrium could, theoretically, prevent implantation. However, because DMPA is highly effective in inhibiting ovulation and sperm penetration, the possibility of fertilization is negligible. No available data support prevention of implantation as a mechanism of action of DMPA.
The life-table first-year failure rates for 8,183 women using Depo-Provera in seven prospective clinical trials were: 0%, 0%, 0.1%, 0.2%, 0.2%, 0.3%, and 0.7%, with a weighted average of 0.3%.
The Pearl Index first-year failure rates for 2,042 women using depo-subQ 104 in three prospective clinical trials were: 0%, 0%, and 0%, with a weighted average of 0%.
The first-year failure rate for 209 women using Depo-Provera in one retrospective survey was: 2.6%.
Trussell's estimated perfect use first-year failure rate for Depo-Provera is the weighted average of failure rates in seven clinical trials: 0.3%.
Prior to 2004, Trussell's typical use failure rate for Depo-Provera was the same as his perfect use failure rate: 0.3%.
In 2004, using the 1995 NSFG failure rate, Trussell increased (by 10 times) his typical use failure rate for Depo-Provera from 0.3% to 3%.
Trussell did not use 1995 NSFG failure rates as typical use failure rates for the other two then newly available long-acting contraceptives, the Norplant implant (2.3%) and the ParaGard copper T 380A IUD (3.7%), which were (as with Depo-Provera) an order of magnitude higher than in clinical trials. Since Norplant and ParaGard allow no scope for user error, their much higher 1995 NSFG failure rates were attributed by Trussell to contraceptive overreporting at the time of a conception leading to a live birth.
Depo-Provera has several advantages:
Depo-Provera may be used by breast-feeding mothers. Heavy bleeding is possible if given in the immediate postpartum time and is best delayed until six weeks after birth. It may be used within five days if not breast feeding. While a study showed "no significant difference in birth weights or incidence of birth defects" and "no significant alternation of immunity to infectious disease caused by breast milk containing DMPA", a subgroup of babies whose mothers started Depo-Provera at 2 days postpartum had a 75% higher incidence of doctor visits for infectious diseases during their first year of life.
A larger study with longer follow-up concluded that "use of DMPA during pregnancy or breastfeeding does not adversely affect the long-term growth and development of children". This study also noted that "children with DMPA exposure during pregnancy and lactation had an increased risk of suboptimal growth in height," but that "after adjustment for socioeconomic factors by multiple logistic regression, there was no increased risk of impaired growth among the DMPA-exposed children." The study also noted that effects of DMPA exposure on puberty require further study, as so few children over the age of 10 were observed.
The WHO Medical Eligibility Criteria for Contraceptive Use and RCOG Faculty of Family Planning & Reproductive Health Care (FFPRHC) UK Medical Eligibility Criteria for Contraceptive Use list the following as conditions where use of Depo-Provera is not usually recommended or should not be used because of an unacceptable health risk or because it is not indicated:
Conditions where the theoretical or proven risks usually outweigh the advantages of using Depo-Provera:
Conditions which represent an unacceptable health risk if Depo-Provera is used:
Conditions where use of Depo-Provera is not indicated and should not be initiated:
It is unclear whether the bone density loss associated with Depo-Provera use is reversible, and if so, how completely. Three studies have suggested that bone loss is reversible after the discontinuation of Depo-Provera, although one notes that bone loss was not reversible in long-term users of Depo-Provera. Other studies have suggested that the effect of Depo-Provera use on post-menopausal bone density is minimal, perhaps because Depo users experience less bone loss at menopause. However, as of 2006, no study has directly examined fracture risk in post-menopausal women who have used Depo-Provera; therefore, the risk is unknown. Pfizer and the FDA recommend that Depo-Provera not be used for longer than 2 years, unless there is no viable alternative method of contraception, due to concerns over bone loss.
Depo-Provera is also used with male sex offenders as a form of chemical castration as it has the effect of drastically reducing sex drive in males.
There was a long, controversial history regarding the approval of Depo-Provera by the U.S. Food and Drug Administration. The original manufacturer, Upjohn, applied repeatedly for approval. FDA advisory committees unanimously recommended approval in 1973, 1975 and 1992, as did the FDA's professional medical staff, but the FDA repeatedly denied approval. Ultimately, on October 29 1992, the FDA approved Depo-Provera, which had by then been used by over 30 million women since 1969 and was approved and being used by nearly 9 million women in more than 90 countries, including the United Kingdom, France, Germany, Sweden, Thailand, New Zealand and Indonesia. Points in the controversy included: