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Oestrogen-free hormonal contraception

Louise Cadman
BSc RGN
Senior Research Nurse/Family Planning Nurse
Cancer Research UK
London
E:louise.cadman@cancer.org.uk

Oestrogen-free hormonal methods have no age limit (even in smokers), can be used during lactation and are safe for women at risk of venous thromboembolism (VTE). This article explores some of the oestrogen-free hormonal contraceptives currently available.
There are five main types of oestrogen-free hormonal contraceptive:

  • The progestogen-only pill (POP).
  • The progestogen-only emergency pill.
  • Intrauterine systems (IUSs).
  • Injectables.
  • Implants.

Progestogen-only pills (POPs)

Mode of action
POPs thicken cervical mucus, making it impenetrable to sperm. The lining of the womb also undergoes thinning (endometrial atrophy), making implantation unlikely to occur. They inhibit ovulation in only 60% of cycles.(1) Cerazette (Organon), a relatively new, higher-dose POP, has been shown to inhibit ovulation in 98% of cycles.(2)

Efficacy and indications
The efficacy of conventional POPs increases with age and the decline in female fertility, and as a result they are best suited to women over 30. By 40 years its failure rate is 0.5 per 100 women-years, but is closer to one per 100 women-years in all ages.(2) However, due to its ovulation inhibition, Cerazette is thought to be more effective in young women.
The POP is useful for women who cannot have oestrogen - for example, smokers over the age of 35, women with diabetes, women with sickle cell disease, women who have developed hypertension or focal migraine while on the combined oral contraceptive pill (COC), and women who are breastfeeding.

Side-effects
The POP has a tendency to cause irregular bleeding patterns. Forty per cent of POP users maintain a normal cycle, 20% are amenorrhoeic (absence of menstruation) and 40% suffer irregular bleeding at variable intervals. Other side-effects are infrequent. The small dose of hormone causes minimal or no metabolic changes, and no association with carcinogenesis has been shown to date.
The POP is associated with the formation of ovarian cysts that are not of great significance other than that they can sometimes cause pelvic pain.

Cautions and contraindications
There is a very small increased risk of ectopic pregnancy in POP users. The POP should be avoided in women with a history of ectopic pregnancy.

Rules for taking the POP
The POP must be taken every day within the same three hours, except in the case of Cerazette, which has a 12-hour window. The POP should be started on day one of the cycle, without the need for additional contraceptive protection.
If a pill is more than three hours late, it should be taken as soon as it is remembered, and then the next one taken on time. Under these circumstances, additional contraceptive precautions  needs to be used, but only for 48 hours.
Broad-spectrum antibiotics have no effect on the POP, and extra contraceptive precautions are therefore unnecessary during treatment with these drugs.
There is a suggestion (although no data) that, in women who weigh over 70kg, the efficacy of progestogen-only methods may be reduced,(3) and that two POPs a day should be given.

Progestogen-only emergency contraception
Levonelle-2 (Schering Healthcare) consists of two tablets that are equivalent to 25 Microval (Wyeth) tablets. These are both given at the same time within 72 hours of unprotected sex. Levonelle is now licensed and available not just on prescription - a single tablet version (Levonelle One Step) has been available to purchase over the counter in pharmacies since November 2004.

Injectable progestogens
There are currently two injectable progestogen preparations in use, namely depot medroxyprogesterone acetate (DMPA or Depo-Provera; Pharmacia) and norethisterone enanthate (NETEN). Of the two, DMPA is the most widely used and will therefore be referred to in this discussion.

Mode of action and efficacy
DMPA is a high-dose progestogen (150mg) given as a deep intramuscular (gluteal or deltoid) injection every 12 weeks. Progestogen is released gradually into the circulation and inhibits ovulation. This results in an efficacy approaching 100%.

Indications
Injectable progestogens, like POPs, are suited to women who cannot take oestrogen. They do not require day-to-day motivation from the user, and offer contraception that is nonintercourse-related. As a consequence, they are ideally suited for those who are forgetful or travel frequently.

Side-effects
Injectable progestogens can reduce menstrual symptoms such as menorrhagia (excessive bleeding), dysmenorrhoea (menstrual pain) and premenstrual symptoms. Due to the inhibition of ovulation, the method is highly suitable for women who have a history of ectopic pregnancy or ovarian cysts.

Cautions and contraindications
Once administered, the dose of hormones cannot be removed, so any side-effects have to be tolerated for three months.
Disturbances of menstruation can occur that may be marked and unpredictable. With repeated injections, however, women tend to become amenorrhoeic; indeed, the majority are likely to achieve this within a year.
After stopping Depo-Provera there is a median delay of fertility of 10 months. Women should be advised to have their last injection approximately six months before a planned pregnancy.
Weight gain may occur, and women who are prone to depression may complain of an increase in severity. However, androgenic effects, such as acne, are less frequent than would be expected with a high-dose progestogen preparation.
A large WHO study published in 1991 showed a slightly increased risk of breast cancer within the first four years of use of injectable progestogens.(4) This may, however, have been attributable to bias in the study. It showed no increase in risk for cervical or ovarian cancer and a protective effect for endometrial cancer.(5)
There has been discussion about the possibility of reduction in bone density with long-term Depo-Provera use. It appears, however, that women who use Depo-Provera are more likely to have other risk factors, such as smoking, low socioeconomic status and family history of the condition. The Committee for the Safety of Medicines (CSM) has recently issued guidance that the use of Depo-Provera for longer than two years or in adolescents and women with significant risk factors for osteoporosis should be considered carefully.(6)

Rules for administering DMPA
The injection of DMPA is normally given in the first five days of the cycle, without the need for extra ­precautions. The injection site should not be rubbed, as this may affect the release of hormone.
It should be noted that, very rarely, pregnancy has occurred at 14 weeks after the last injection. For this reason, the manufacturer advises that pregnancy should be excluded if the injection interval is greater than 89 days, and that extra precautions should be taken for seven days.

Implants

Mode of action and efficacy

Implanon (Organon) is a subcutaneous progestogen-only implant. It consists of a single, silastic rod that releases 30-40mg of etonogestrel per day and lasts for three years. It is designed to achieve complete inhibition of ovulation, and, so far in the worldwide clinical trials, there has not been a single pregnancy.

Rules for administering
Implanon is effective within 24 hours of insertion. The inserter is the size of a blood transfusion needle, and the procedure takes, on average, two minutes. Removal, using a "pop-out" technique, takes three minutes. Implanon is rapidly reversible - within a week of removal, blood levels of hormone are ­undetectable.

Cautions and contraindications
Like both injectables and the POP, its main side-effect is irregular bleeding, which tends to settle down after a few months. Around 21% of women using Implanon will become amenorrhoeic.

Intrauterine systems

Mode of action and efficacy
Mirena (Schering Healthcare) is a T-shaped device that is inserted into the uterus, where it remains, and releases 20mg of levonorgestrel per day. The device lasts for five years. Its mechanism of action is mainly related to atrophy of the endometrium, and the majority of women will ovulate at least occasionally. It has a failure rate of around 0.2 per 100 woman- years.

Indications
The intrauterine system is particularly suited to women who have dysmenorrhoea, menorrhagia (for which it has a licence) or long menstrual periods. It is not associated with an increased risk of ectopic pregnancy or pelvic inflammatory disease.
Mirena is useful for perimenopausal women who still need contraception, as it is now licensed to provide the progestogen part of hormone replacement therapy.

Side-effects
The use of Mirena results in a major reduction in menstrual flow and dysmenorrhoea. Irregular, although light, bleeding occurs, particularly in the first few months of use, and only about 10-15% of women become amenorrhoeic.

Cautions and contraindications
Fitting Mirena in nulliparous women can be difficult as the hormone-containing stem of the device is slightly wider than that of a copper intrauterine device.

References

  1. Rice CF, et al. A comparison of the inhibition of ovulation achieved by ­desogestrel 75mcg and levonorgestrel 30mcg daily. Hum Reprod 1999;14:982-5.
  2. Korver T, for collaborative group.A double blind study comparing the contraceptive efficacy, acceptability and safety of two progestogen-only pills containing desogestrel 75mcg/day or levonorgestrel 30mcg/day. Eur J Contracept Reprod Health Care 1998;3:169-78.
  3. Vessey M. Oral contraceptive failures and body weight: findings in a large cohort study. J Fam Plann Reprod Health Care 2001;27(2):90-1.
  4. WHO Collaborative Study of Neoplasia and Steroid Contraceptives. Breast cancer and depot-­medroxyprogesterone acetate:a multinational study. Lancet 1991;338:833-8.
  5. WHO Collaborative Study of Neoplasia and Steroid Contraceptives. Reports relating to ovarian, ­endometrial and liver cancers.Int J Cancer 1991;49:182-95.
  6. MHRA statement on Depo-Provera, 19 November 2004. Available from URL: http://medicines.mhra.gov.uk/ ourwork/monitorsafequalmed/safetymessages/urgent.htm