Rationale: Although ovulation can occur as early as day 10 of the menstrual cycle, this is rare (234). Fertile ovulation is very uncommon before day 12 (269). Intercourse 5 days before ovulation may have as much as a 5% chance of resulting in pregnancy (66). However, since, experts believe, there are few fertile ovulations before day 13, there is only a very small chance that intercourse on day 7 of the cycle could result in pregnancy (269).

In general, use of DMPA within the first 7 days after the start of a woman's normal menses would assure that the probability of the woman's already being pregnant, or becoming pregnant, is extremely low (66, 104, 238, 269).

Although injectable progestins have no known teratogenic effects, avoiding the risk of fetal exposure is preferable on general principles. In addition, one study has suggested that in utero exposure may increase the risk of low birth weight (28, 212, 251).

Recommendation: For a woman having menstrual cycles, no back-up method is needed if she is in the first 7 days of her menstrual cycle and is still menstruating. If she is in the first 7 days of her cycle but is not menstruating, some programs may recommend use of a back-up method for 1 week. Injectables may be started any time you can be reasonably sure the woman is not pregnant (see How to Be Reasonably Sure the Woman Is Not Pregnant). However, if injections are started after day 7 of a regular cycle, a back-up method (or abstinence) may be needed (see below).

Rationale: It is probable that progestin-only injections effectively thicken cervical mucus within 24 hours. Consistent with this theory, progestin-only pills have been shown to produce a thickened mucus with low sperm penetration within 3 to 4 hours after pill ingestion. Natural progesterone also causes cervical mucus to become scant, thick, and sticky, decreasing or inhibiting sperm penetration, usually within 24 hours but sometimes within 48 hours. Clinical judgment is also consistent with this theory (84, 126, 193, 270, 280, 316).

DMPA and NET EN consistently inhibit ovulation (191, 303).

Recommendation: Although there is good reason to believe the effect on cervical mucus will promptly provide contraceptive protection within 24 hours, it may be prudent to consider a back-up method for up to 7 days.

(See Question 2 for postpartum initiation and Question 3 for postabortion initiation.)

Rationale: Some programs might recommend a back-up method for women who are not menstruating at the time of progestin-only injectable initiation because there is a very slight risk of conception from unprotected intercourse on day 7 of the cycle.

* In breastfeeding women, bleeding in the first 56 days (8 weeks) postpartum is NOT considered "menstrual" bleeding because it is not preceded by ovulation.

Rationale: Risk of pregnancy during lactational amenorrhea is very low: less than 2% in the first 6 months postpartum if fully breastfeeding; less than or equal to 7% in the first 12 months. If the fully or nearly fully breastfeeding woman remains amenorrheic, her risk of pregnancy is about the same as her risk with other modern contraceptive methods (22, 147, 214).

Recommendation: If she does not want to rely on LAM, ideally wait at least 6 weeks postpartum to initiate injectable progestins.

Rationale: Based on animal studies and observed fluctuations of human sex hormones in the first 6 weeks of life, plus the immaturity of the neonatal liver for the metabolism of exogenous steroids, it is considered prudent to wait to initiate progestin-only contraceptives until a breastfeeding woman is at least 6 weeks postpartum (112, 289).

Studies have detected no clinically measurable effects on the health or growth of breastfed babies of women who begin using progestin-only injectables at 6 weeks postpartum (135, 213, 309, 311, 318).

Rationale: While there may be a theoretical concern about increased thrombogenic effect with COC use in the first week postpartum, there is no known clinical thrombogenic effect of progestin-only contraceptives; therefore injectable progestins can be safely used immediately postpartum, for nonbreastfeeding women (36, 86, 303).

Rationale: Fertility returns almost immediately postabortion (spontaneous or induced): within 2 weeks for first-trimester abortion and within 4 weeks for second-trimester abortion. Within 6 weeks of abortion, 75% of women have ovulated (164, 206).

As noted above, there is no known clinical thrombogenic effect of progestin-only contraceptives; therefore injectable progestins can be safely used immediately postabortion (spontaneous or induced) (36, 86, 303).

Rationale: After discontinuing DMPA, about 50% of women conceive by 7 months (i.e., 10 months after the last injection). This time delay to conception is approximately 4 months longer than the time it takes for women who discontinue COCs, IUDs, or barrier methods to conceive. Residual amounts of DMPA will remain in circulation for about 7 to 9 months after an injection, at which time serum levels of DMPA become undetectable. By about 2 to 3 years after discontinuation of DMPA, the proportion of women who have conceived is virtually the same as for those who have discontinued use of IUDs, diaphragms, and COCs. The delay in return to fertility with NET EN is presumed to be no more than with DMPA (21, 127, 191, 239, 303).

Rationale: DMPA confers many noncontraceptive benefits including decreased menstrual blood loss as well as protection against endometriosis, acute pelvic inflammatory disease (PID), ectopic pregnancy, and, of particular importance to older women, protection against endometrial cancer. DMPA may also inhibit intravascular sickling—an additional benefit to women who have sickle cell disease. Other effects that may be attributed to DMPA use include a slight increase in weight and slight (not clinically significant) alterations in plasma lipid profiles. A theoretical risk of osteoporosis is currently under study (54, 55, 137, 177, 208, 247, 258, 270).

Because women greater than 35 years of age are at increasing risk for endometrial (and ovarian) cancer, it is particularly important to:

• Carefully evaluate irregular bleeding before administering the injectable and
• More carefully consider cancer as a possible cause if the woman returns with irregular bleeding after prolonged amenorrhea.

Rationale: Amenorrhea while on progestin-only contraceptives is evidence of lower estrogen levels, and estrogen is necessary for the development and maintenance of strong bones (to prevent osteoporosis). The peak strength (density) of spinal bone is reached by girls around age 16; the greatest increase in bone density occurs in the first 2 years post-menarche.

Rationale: There is no cumulative effect of injectable progestins; the time required to clear the drug from the body is the same after multiple injections as after a single injection.

Rationale: It is reasonable to expect amenorrhea among injectable progestin users, and the likelihood of amenorrhea increases with increased duration of progestin-only injectable use (50% at end of first year, two-thirds of women by the end of second year of use). Women who are counseled about this possible side effect will be less concerned if they experience extended amenorrhea.

Recommendation: The question of whether progestin-only injectables may be related to osteoporosis is under study. In theory, this may be a particular concern for older women with prolonged amenorrhea. (See Question 4 concerning amenorrhea due to DMPA before age 16.)

Rationale: Extended amenorrhea resulting from the use of injectable progestins is due to endometrial atrophy. There is no risk of endometrial hyperplasia. In fact, DMPA is protective against endometrial cancer.

• Up to 2 weeks late and possibly up to 4 weeks late depending on the population, or
• Up to 4 weeks early, although this is not ideal.

Recommendation: For NET EN, on a 2-month schedule, it is acceptable to give the next injection:

• Up to 1 week late and possibly up to 2 weeks late depending on the population, or
• Up to 2 weeks early, although this is not ideal.

Recommendation: If a client comes in after the grace period, advise her that delays in obtaining progestin-only injections increase the risk of pregnancy and in utero exposure to the progestin-only injectable. It is acceptable to give the progestin-only injection if you can be reasonably sure she is not pregnant (see How to Be Reasonably Sure the Woman Is Not Pregnant). Although there is good reason to believe the effect on cervical mucus will promptly provide contraceptive protection within 24 hours, it may be prudent to consider a back-up method for up to 7 days. Reschedule the next injection (for 3 months with DMPA or 2 months with NET EN).

Rationale: It has been shown that the time it takes for progestin levels to be insufficient for contraception may vary somewhat from population to population. Studies show that Thai women seem to metabolize DMPA rapidly. Additionally, weight has also been shown to have an independent influence on progestin levels (in heavier women the contraceptive effects last longer) (19, 87, 94, 304).

For prolonged spotting or moderate bleeding (equivalent to normal menstruation but longer in duration), the first approach should be counseling and reassurance. It should be explained that in the absence of evidence for other diseases, irregular bleeding commonly occurs in the first few months of use of injectable progestins.

If counseling and reassurance are not sufficient for the woman and she wishes to continue the method, the following management approaches may be tried:

• Short-term (for 7 to 21 days) COCs or estrogen, or
• Ibuprofen (or similar nonsteroidal anti-inflammatories other than aspirin), or
• If the previous injection was given more than 4 weeks ago, giving another injection at this time may be an effective approach.

Recommendation: Heavy bleeding (greater than normal menstruation) is uncommon; it can usually be controlled by administration of increased doses of COCs (or estrogen). Some women will require stopping the use of injectable progestins due to medical reasons for excessive bleeding or due to the client's preference.

If suspected, abnormal conditions that cause prolonged or heavy bleeding should be evaluated and treated as appropriate.

Some prolonged or heavy bleeding may fail to be corrected, and injections may need to be discontinued.

Evaluate and address anemia if indicated. Give nutritional advice on the need to increase the intake of iron-containing foods.

Do not perform uterine evacuation unless another medical condition is suspected. (Vacuum aspiration is generally the preferred method of uterine evacuation.)

Rationale: Management of prolonged or heavy bleeding may be achieved by:

• Rebuilding endometrium with COCs/estrogen, or
• Ibuprofen* (which blocks prostaglandin synthesis and thus decreases uterine bleeding) (61, 303, 312).

* Nonsteroidal anti-inflammatory drugs (e.g., ibuprofen) should be used instead of aspirin because of aspirin's stronger and longer-lasting inhibitory effects on platelet aggregation (aspirin promotes bleeding) (5, 83).

Rationale: One study found a decrease in the number of days of bleeding and/or spotting in women immediately following each re-injection every 12 weeks. Another study found no significant difference in the bleeding patterns of adolescents re-injected at 6 weeks compared with those re-injected at 12 weeks. However, there were several limitations to the studies, and more research is needed (111, 313).

Rationale: Nurses, midwives, and other community health workers can be appropriately trained to initiate and resupply injectable progestins (303).

• Cleaning of the injection site;
• Use of sterile needles and syringes (single use, disposable needles and syringes are preferred);
• If sterilization of reusable needles and syringes is impossible, decontamination with bleach followed by high-level disinfection—if correctly executed—may be used; and
• Safe disposal of single-use needles and syringes.

Another concern is the increasing problem of transmission of hepatitis B and AIDS viruses to clients, health care providers, and clinic staff, especially cleaning and housekeeping personnel. To minimize this risk whenever possible single-use (disposable) needles and syringes should be used. If reusable needles and syringes are used, they should be decontaminated immediately after use by soaking in 0.5% chlorine solution or other locally available and approved disinfectant. These practices, when combined with the proper disposal of single-use needles and syringes, protect clinic staff, especially cleaning and housekeeping personnel, from contracting hepatitis B or AIDS following accidental needle sticks. Following decontamination, reusable needles and syringes should be thoroughly cleaned and finally, sterilized or high-level disinfected (272).

Rationale: The deltoid is generally more acceptable to the client and more accessible for service providers (303).

Some providers prefer to offer NET EN in the gluteal muscle because the oil-based NET EN requires a larger-bore needle and may be painful.