Introduction Injectable contraceptives contain hormonal drugs that provide women with safe, highly effective, and reversible contraceptive protection. Two types of injectable contraceptives : (1) Progestogen-only formulations that contain a progestogen hormone and are effective for 2 or 3 months; and, (2) Combined formulations that contain both a progestogen and an estrogen and are effective for 1 month Progestogen -only formulations • Consist of DMPA (depot med- roxyprogesterone acetate) and NET-EN (norethisterone enanthate). • DMPA is the injectable formulation most widely used worldwide. • DMPA is injected every 3 months. • NET-EN is injected every 2 months. Combined formulations – The most extensively studied formulations are known by their brand names, Mesigyna; – Monthly injectable. – Mesigyna contains the same progestogen as NET-EN.& contains an added estrogen. Combined formulations Administered by a deep intramuscular injection into the muscle of the arm or buttock and are effective immediately, provided they are taken at specified times All injectable contraceptives are slowly absorbed into the bloodstream from the injection site, with the body maintaining a sufficient level of hormone to provide contraception for 1 to 3 months, depending on the type of injectable used Name Active Duration of Common ingredients effect trade names DMPA 150 mg medroxyprogesterone 90 days Depo-Provera, (progestogen- only) acetate in an aqueous Depo-Clinovir, microcrystalline suspension others NET-EN 200 mg 60 days Noristerat, (progestogen norethisterone Norigest, enanthate Doryxas, and -only) in an oily preparation others Mesigyna 50 mg 30 days Mesigyna, norethisterone (combined) enanthate and Norigynon 5 mg estradiol valerate PROGESTOGEN ONLY INJECTABLES Mode of Action • The immediate action of progestagen-only injectables (POIs) is to thicken cervical mucus, which then presents an obstacle to sperm penetration. • Also, ovulation is impaired. • There are additional changes in the endometrium that make it unfavourable to implantation; however, the first two effects make fertilisation highly unlikely. Efficacy The reported failure rates of POIs are low, and come within the narrow range of 0.1% to 0.6%. Beneficial Effects • Prevention of pregnancy • A single injection of a POI can provide highly effective protection against pregnancy for two or more months, depending on the formulation. • Delivery is simple, independent of coitus, and ensures periodic contact with medical or other trained health personnel. • This is a suitable method for women in whom oestrogens present health risks – eg, those with a history of thromboembolic disorders - and those who have had side effects with the use of oestrogens. Non-contraceptive health benefits Clear benefits • Sickle cell disease: In a two-year trial, women with sickle cell disease using DMPA had significantly fewer crises than women given a placebo. • Anaemia: POIs can increase haemoglobin concentration, mainly by reducing menstrual blood loss. Non-contraceptive health benefits Possible benefits 1. Endometrial cancer: • In a World Health Organization (WHO) study, women who had ever used DMPA had one-fifth the risk of developing endometrial malignancy observed in women who had not used DMPA. • The results, although not statistically significant, support the hypothesis that use of DMPA might protect against this form of cancer. 2. Other: • The use of POIs possibly protects against pelvic inflammatory disease (PID), seizures in women with epilepsy, uterine myoma, and endometriosis. PROGESTOGEN ONLY INJECTABLES SIDE EFFECTS Menstrual irregularities • DMPA and NET-EN are associated with disruptions of the menstrual cycle including amenorrhoea, prolonged menses, spotting between periods, and heavy bleeding. • Less than one-third of women receiving DMPA report having normal menstrual cycles during the first year of use. Menstrual irregularities • Amenorrhoea is the most common side-effect and its occurrence increases with duration of use from about 50 % of DMPA users by the end of one year to 80% by the end of 5 years. • Women using NET-EN are less likely to experience amenorrhoea. Menstrual irregularities • Heavy bleeding is uncommon (occurs in 1-2% of users), and prolonged bleeding is seldom heavy enough to be a threat to health. • Any woman who reports prolonged or heavy bleeding may need to be evaluated for anemia. • Anaemia treatments include nutritional advice & an appropriate dosage of oral iron tablets. Menstrual irregularities • Treatments for heavy bleeding include non-aspirin anti-inflammatory drugs such as ibuprofen, short-term use of combined oral contraceptives or estrogen, or early administration of the next injection (not sooner than 4 weeks after the previous injection). • If these measures are not effective or the woman’s health is threatened, POIs should be discontinued. Other Side-Effects • After menstrual changes, weight gain, headache, and dizziness are the next most common side-effects reported. • Most users of POIs put on weight and this is a common reason for discontinuation. • The average DMPA user gains 1.5–2.0 kg in the first year and some users continue to gain weight thereafter at about the same rate. • In clinical trials, between 3% and 19% of users of injectables have reported headache or dizziness. Few women discontinue for these reasons. Possible Carcinogenicity • Clinical studies have found no association between DMPA use and cervical, ovarian, or liver cancers, • And have confirmed a substantial protective effect against endometrial cancer. • Studies have found no overall increase in risk of breast cancer. • Although some studies have indicated a small increased risk of breast cancer in some younger women following initial exposure, the studies show no trend toward increased risk among more long-term users. Bone density • Findings to date suggest a relatively small and reversible effect, with no serious health risk for women of any age. • At present, medical experts recommend no restriction on use of injectables by adolescents over age 16. • Changes in calcium uptake by bone and decreases in urinary calcium excretion have been documented and there is a suggestion of a relation between long term use of DMPA and low bone mass. Effect on fetal exposure • There are no known adverse effects of fetal exposure to injectables. • Studies of teenage children who were exposed to DMPA in utero show no significant differences in health, growth, or sexual development compared to other children. • Progestogen-only injectables can be used by breastfeeding women at 6 weeks postpartum without adverse effects on nursing infants. Effect on Metabolism • The only metabolic effect of undoubted clinical importance is weight gain. • - Minor alterations of lipid metabolism, fluid/nitrogen balance, glucose tolerance, steroid metabolism, and immune function have been recorded but seem to be of no clinical significance. • - Fewer data have been published on the metabolic effects of NET-EN, but its effect on most biochemical functions appears to be similar to that of DMPA. Cardiovascular Effect • Data are insufficient to indicate whether there is any relation between DMPA use and cardiovascular complications. • Results of a WHO study suggest that there is little or no increased risk of cardiovascular disease associated with the use of progestagen-only injectables, although further investigation is needed into a possible increased risk of stroke among women with high blood pressure. RETURN OF FERTILITY • Fertility is not impaired after discontinuation of DMPA or NET-EN although its return is delayed. • The average time between the last DMPA injection and conception is about nine months, including the three months during which the injection is effective. • More than 80% of women become pregnant within one year of discontinuing DMPA and 90% within two years. • The few data on NET-EN suggest that fertility returns more quickly with this agent. World Health Organization (WHO) developed eligibility criteria for the use of various contraceptive methods. • Category 1: A condition for which there is no restriction for the use of the contraceptive method. • Category 2: A condition where the advantages of using the method generally outweigh the theoretical or proven risks. • Category 3: A condition where the theoretical or proven risks usually outweigh the advantages of using the method. • Category 4: A condition which represents an unacceptable health risk if the contraceptive method is used. Contra-indications (category 4): POIs should not be used in the presence of: 1. Confirmed or suspected pregnancy 2. Malignant disease of the breast Conditions requiring careful consideration (category 3): POIs should generally not be used in the presence of: 1. Diabetes with vascular disease or of >20 years’ duration 2. Cerebrovascular or coronary artery disease 3. Acute liver disease 4. 4.benign or malignant liver tumours 5. Severe hypertension/ (BP>180/110 mm Hg) 6. Hypertension with vascular disease 7. Focal migraine . 8. severe cirrhosis Other Conditions (category 2) - Women with mild to moderate hypertension, diabetes (without vascular complications), hyperlipidaemias, or mild (compensated) cirrhosis can generally use POIs. - Careful screening and appropriate monitoring will allow the benefits of using POIs to outweigh any potential risks. COMBINED INJECTABLE CONTRACEPTIVES Mode of Action • Combined injectable contraceptives (CICs) exert their contraceptive effect mainly by suppressing ovulation. • In addition, thickening of the cervical mucus (mainly due to the progestagen) presents an obstacle to sperm penetration. • The receptivity of endometrium to the blastocyst is also reduced. Efficacy • In clinical trials, Cyclofem /Cycloprovera and Mesigyna/Norigynon have both proved highly effective contraceptives • With 12-month failure rates of 0.2% or less for Cyclofem and 0.4% for Mesigyna. Beneficial Effects • A single injection of a CIC can provide highly effective protection against pregnancy for one month. • Delivery is simple and independent of coitus, and in general CICs are associated with better cycle control than POIs. Side-Effects • In clinical trials, side-effects of CICs included irregular bleeding, amenorrhoea, heavy bleeding, prolonged bleeding, headaches, dizziness, and body weight changes. • However, these side-effects are much less common than with the use of POIs. Return of Fertility • The return of fertility following CIC use is noticeably shorter than that observed for POIs. • More than 50% of women become pregnant within six months of discontinuing CICs and 80% within one year. Eligibility Criteria Until sufficient clinical data become available, the eligibility criteria for the use of combined injectable contraceptives are based on data from combined oral contraceptives Adolescents Injectable contraceptives have important advantages in adolescents; however, in those under 16 years of age there are concerns regarding the hypo-oestrogenic effects of POIs, which may affect the post-menarche increase of bone mineral density. Women Over 35 • POIs and CICs can be used by most healthy women over 35. • Any increase in risk of cardiovascular disease will be minimal for these women if they do not smoke and have no other risk factors, such as hypertension or diabetes. Postpartum (in Breast feeding Women) • If a woman wishes to start injectable contraception during breastfeeding a POI should be recommended. • DMPA and NET-EN have no apparent negative influence on milk production or the duration of lactation; and infants whose mothers have received DMPA while breastfeeding seem to develop normally, both physically and mentally. Postpartum (in Breast feeding Women) • The question of possible consequences of the transfer of the injectable steroid to the breastfed infant has yet to be resolved. • The amounts of steroid transmitted in the milk and absorbed by the infant are known to be small. Postpartum (in Breast feeding Women) • Short-term follow-up studies of children breastfed by mothers using progestagen- only contraceptives have given reassuring results, but longer-term studies are yet to be evaluated. • It is recommended that breastfeeding women should not start POIs before the sixth week postpartum. Postpartum (in Breastfeeding Women) • There are no data on the effects of CIC formulations on the quantity and quality of breast milk or the duration of lactation. • Until such data become available, CICs should generally be withheld until six months after delivery or until the infant is weaned, whichever is the earlier Postpartum (in Non-Breast feeding Women) • To avoid increasing the risk of thromboembolic complications in the postpartum period, CICs should not be used during the first three weeks after delivery. • After 21 days, blood coagulation and fibrinolysis are essentially back to normal. • POIs can be started at any time after delivery. Drug Interaction • Drugs that induce liver enzymes may lessen the efficacy of hormonal contraceptives. • Such drugs which are commonly used in long-term treatments include the antibiotics rifampicin and griseofulvin and the anticonvulsants phenytoin, carbamazepine, and barbiturates. Prevention of STD/HIV Transmission • Strict aseptic techniques should be maintained when giving the injections to avoid the risk of transmitting any infection including HIV. • Injectable contraceptives do not protect against STD/HIV infection. • Therefore, when there is a risk of sexual transmission of infection, condoms should always be used in addition to injectable contraceptives. Elective Surgery • It is advisable to stop using CICs about four weeks before elective surgery that will involve prolonged immobilisation, and to restart them two weeks after the woman has returned to mobility. • Alternative effective contraception, including POIs, should be advised during this time. • In emergency procedures, the surgeon may consider prophylactic anticoagulant measures Sickle Cell Disease • Either POIs or CICs can be used by women with sickle cell disease but POIs are a more suitable choice. • In addition to their contraceptive effect, there is some evidence of benefit on the disease itself. Counselling • Clients considering the use of injectable contraception should be clearly informed about the advantages and disadvantages of the agents, their side-effects, their cost, and the alternative contraceptive options. • Where once-a-month injectables are available, clients should be told about the differences between these injectables and POIs. • Women who desire a rapid return to fertility on discontinuation of their contraceptive should be advised to use CICs where available or another method. some misconceptions about injectables Do injectable contraceptives cause infertility ? No. Although a woman's return to fertility can be delayed after injectables are discontinued, injectables do not damage fertility. Do injectable contraceptives increase cancer risks ? No. Overall increase in cancer risk has not been demonstrated in long- term, multicountry studies of injectable users. When amenorrhea occurs, does menstrual blood build up in the body, leading to disease ? No. Amenorrhea is not a health risk. It does not cause blood to build up in the body. Can injectable contraceptives transmit disease ? • No. • Injectable contraceptives are sterile preparations that are free from disease- causing agents. • Contaminated needles and syringes used to administer injectables can transmit disease, however. special injection techniques • Injectable contraceptives are administered using deep intramuscular injection techniques. • The injection site should not be massaged afterwards, since this may accelerate absorption of the drug. • Because DMPA is an aqueous suspension, a DMPA vial must be shaken vigorously before it is loaded into the syringe, to resuspend any active ingredient in the bottom of the vial. • The syringe should then be checked to ensure that it contains the correct dosage. • NET-EN is an oil-based solution that needs special care to ensure that all the solution is both loaded and injected without leakage. • Warming the vial to body temperature makes it easier to draw into the syringe. • Since Mesigyna is an oil-based solution similar to NET-EN, the same attention to leakage applies. When can the initial injection be given ? Progestogen -Only Injectables • DMPA and NET-EN : • During the first 7 days of the menstrual cycle. • Injectables will be immediately effective. • Immediately after abortion. • At other times in a menstrual cycle as long as the possibility of pregnancy is ruled out. • At 6 weeks postpartum. Combined Injectables Mesigyna • During the first 5 days of the menstrual cycle. • Injectables will be immediately effective. • Immediately after abortion. • At other times in a menstrual cycle as long as the possibility of pregnancy is ruled out. • At 6 months postpartum. Margin for the follow-up re-injection •Progestogen-Only Injectables DMPA and NET-EN: up to 2 weeks (14 days) early or late • Combined Injectables Mesigyna: Up to 3 days early or late Breast feeding • Progestogen-Only Injectables DMPA and NET-EN: Suitable for women who are breastfeeding at 6 weeks postpartum. • Combined Injectables Mesigyna: Not suitable for women who are fully breast feeding until 6 months postpartum.