Progestogen-only Injectable Contraceptives

The Department of Health is promoting the use of long-acting, reversible contraceptives as a method of family planning. It has been added as a Quality and Outcomes Framework (QOF) target.¹

A progestogen-only injectable contraceptive (POIC) is a long-acting, reversible contraceptive. A synthetic progesterone or progestogen is slowly released into the systemic circulation following intramuscular injection.

There are 2 forms of depot injection currently available on the UK market:

• Depo-Provera® is depot medroxyprogesterone acetate (DMPA) aqueous suspension 150 mg in 1 ml.²
• Noristerat® is norethisterone enantate (oenanthate) 200 mg in 1 ml in an oily liquid.³

• Its main mechanism of action is to suppress ovulation.
• It also makes the endometrium unsuitable for implantation if fertilisation occurs.
• It also increases the viscosity of cervical mucus, making the mucus less easily penetrable to sperm.⁴

3% of women aged 16-49 use the injection as their method of contraception.⁵ This percentage has been stable for some time.

Depot contraceptives are available only for women in the UK, but trials of monthly testosterone injections for men have been undertaken in China.⁶

• Provided that the Depo-Provera® is given on a regular basis every 12 weeks (8 weeks for Noristerat®), there is a very low failure rate - fewer than 4 per 1,000 women over 2 years.⁷
• As a long-acting contraceptive, Depo-Provera® has a greater efficacy than the oral contraceptives.⁸
• Neither obesity, nor the use of liver enzyme-inducing medication affect the failure rate of Depo-Provera®. The efficacy of Noristerat® is lowered by enzyme-inducing drugs. Broad spectrum antibiotics do not affect the efficacy of either injectable.

• Depo-Provera® is suitable for those who want a reliable but reversible form of contraception that does not require daily vigilance like oral contraceptives, or action at the time of intercourse like barrier contraceptives. It should only be used in adolescents (aged 12-18) after other methods have been considered unsuitable or unacceptable.^2,9
• It is a useful alternative for women who need a reliable form of contraception but who have contra-indications to oestrogen therapy in the combined oral contraceptive . Long-acting reversible contraceptives are recommended by NICE on the grounds of their low failure rates and better cost-effectiveness than short-acting methods (e.g. oral contraceptive pill, barrier methods).⁷
• Noristerat® is for short-term use (maximum of 2 injections), e.g. until vasectomy becomes effective.

(see individual drug monographs for complete list)

• Hormone-dependent cancers and any form of breast cancer
• Current hydatidiform mole or choriocarcinoma (until hCG undetectable)
• Current severe impairment of liver function or history of liver adenoma or steroid-induced cholestatic jaundice
• History of severe arterial disease or very high risk factors - risk of thrombosis and arterial disease may be increased
• Acute porphyria, even if no history of active disease
• Pregnancy - should be excluded before injection (a history of recent normal menstruation is adequate)
• Noristerat® may not be used during breast-feeding of neonates with severe or persistent jaundice
• Unexplained vaginal bleeding
• Osteoporosis is an absolute contra-indication:
  • Risk factors for osteoporosis are a relative contra-indication
  • Depo-Provera® should be given to adolescents and women over 40 years old only if other methods of contraception are unsuitable, because of the possible effect on bone mineral density (BMD)⁷
• Contraceptive injections are not appropriate for those who may wish a return to fertility in the near future:
  • Whilst contraception can be assured for 3 months after the injection, some women may not be able to conceive for 10 to 15 months after having the last injection. Median delay to conception was 5.5 months plus the estimated duration of the effect of the last injection of Depo-Provera®, 3 months for oral contraceptives and 4.5 months after discontinuing the intra-uterine contraceptive device (IUCD).
  • Long-term there was no difference in failure to conceive.¹⁰
• Anticoagulant therapy increases the risk of haematoma at injection site - concomitant use should be avoided⁴

Progestogen only contraception, whether in the form of progestogen-only pills (POP), depot injections or slow release implants, seems to have an extremely good safety profile although, in many studies, larger numbers would be preferable for more reliable results.¹¹

Irregular bleeding

This is very common:

• Women often become amenorrhoeic (particularly when using DMPA¹²), but persistent bleeding can occur.⁷ Counselling before administration greatly improves tolerance for such matters.¹³
• When Depo-Provera® is given before 6 weeks postpartum, there is a risk of heavy and prolonged bleeding.
• If menstrual problems are difficult, it is possible to overcome intermenstrual bleeding and to establish a cycle by giving oral ethinyl oestradiol, usually at 10 to 20 micrograms daily, but this negates the advantage of an oestrogen-free product.

Bone mineral density

Depo-Provera® causes a reduction in bone mineral density:

• This is mostly in the first 2 years and then it stabilises.¹⁴
• It does largely recover when injections are stopped.¹⁵
• There is no evidence of an increase in fracture rates.⁷
• Depo-Provera® is licensed for long-term use, but it is recommended that the benefit/risk profile for an individual be re-evaluated if she wishes to continue using it for more than 2 years.

Lipid metabolism

There may be a reduction in serum LDL cholesterol levels,^2,4,16 but current use of injectables has not been shown to increase cardiovascular, cerebrovascular event, venous thromboembolism or acute MI risk. In the current WHO medical eligibility criteria recommendations, DMPA and norethisterone are category ‘3’ for women with multiple risk factors for arterial cardiovascular disease (CVD), current venous thromboembolism (VTE), ischaemic heart disease or history of stroke, i.e. the risks of using POICs may outweigh the benefits.¹⁷

Breast cancer

Breast cancer incidence is slightly raised during and for up to 10 years after use of injectable contraceptives:

• For those stopping by age 30 after 5 years use of POIC, there would be an estimated 2-3 extra cases (additional to the 44 cases of breast cancer per 10,000 women in this age group never exposed to oral contraceptives).
• For those stopping by age 40 after 5 years use, there would be an estimated 10 extra cases diagnosed up to 10 years afterwards (additional to the 160 cases of breast cancer per 10,000 never-exposed women in this age group).

This may be because of patient selection - risk factors for breast cancer are a contra-indication to oestrogen-containing methods of contraception.⁴

Mastalgia (breast tenderness) is common.

Weight gain

Weight gain of up to 3 kg in one year may occur.⁷

Congenital malformation

Increased association of polysyndactyly has been reported among infants of DMPA users relative to the other groups.¹⁸ However in five out of the ten polysyndactyly cases, the last injection of DMPA occurred more than 9 months before conception and only three cases had definite gestational exposure.

They also report that infants from accidental pregnancies occurring 1-2 months after a 150 mg Depo-Provera® injection, may be at increased risk for low birth weight and death.^2,19 However such pregnancies are uncommon.

• Depo-Provera® DOES NOT increase the risk of cervical carcinoma , ovarian carcinoma or liver tumours. Risk of endometrial carcinoma is reduced.¹³
• Contraceptive injections give protection against ectopic pregnancy and functional ovarian cysts, because ovulation is inhibited.
• Neither Depo-Provera® nor Noristerat® affect blood pressure.
• Most of the evidence shows that previous concerns about raised insulin levels with Depo-Provera® are unfounded.⁴
• In women with epilepsy , frequency of seizures may be reduced while using Depo-Provera®.⁷
• Acne vulgaris, depression and headaches are not associated with the injection.⁷

Pre-Injection counselling⁷

• Always take a full medical history - family, menstrual, contraceptive and sexual history.
• Always give full counselling about the injection's prolonged action, delayed return to full fertility and possible side-effects, e.g. menstrual irregularities, loss of bone mineral density etc; backed up with patient information leaflet. Once an injection is given, clearly it cannot be removed and its effects will last for 3 months.
• Promotion of safer sex and assessment of risk of sexually-transmitted infections should form part of the consultation. Screening for sexually transmitted infections should be advised if appropriate.

Route of injection

• Depot injections are given by deep intramuscular injection. Depo-Provera® is given every 12 weeks into the gluteal muscles (preferred), deltoid muscles or the lateral thigh. Noristerat® is given every 8 weeks - always into gluteus maximus.

Timing⁷

• Injections should be started on or before the 5th day of the menstrual cycle. If it is given later than day 5, barrier contraceptives should be used for the next 7 days.
• It can be given at any time postpartum. After 1st or 2nd trimester abortion it can be given immediately, or later if necessary.
• Repeat injections can be given up to 5 days late without the need for additional contraception. If it is given after this time, pregnancy should be excluded and additional contraception used for 14 days.