Contraception




Combined hormonal contraceptives

Advantages

  • less dysmenorrhoea and menorrhagia;
  • less PMT;
  • fewer fibroids or functional ovarian cysts;
  • less benign breast disease;
  • reduced risk of ovarian and endometrial cancer;
  • reduced risk of PID, which may be a risk with intra-uterine devices.

OCPs should not be continued after age 50.

Oestrogen content

  • oestrogen content ranges from 20 to 40µg;
  • aim for lowest dose which gives good cycle control;
  • ethinylestradiol 30 or 35µg is appropriate for standard use
  • low strength (ethinylestradiol 20µg) may be appropriate for women with risk factors for circulatory disease.

Phased preparations

  • combined OCPs with varying amounts of oestrogen and progestogen are 'biphasic' and 'triphasic';
  • generally for women who do not have withdrawal bleeding or have breakthrough bleeding with monophasic products.

Extended cycles

Peri-menopausal women may develop vasomotor symptoms during hormone-free days with cyclical preparations. Extended cycle (e.g. 3-monthly) or continuous regimens are sometimes used.

Third-generation progestogens

  • desogestrel, drospirenone, gestodene and norgestimate;
  • may be considered if others cause side-effects (such as acne, headache, depression, weight gain, breast symptoms, and breakthrough bleeding);
  • desogestrel and gestodene have been associated with increased risk of VTE;
  • drospirenone has anti-androgenic and anti-mineralocorticoid activity - hyperkalaemia is possible side effect.

Some suggest that progestogens may be divided into those which have anti-oestrogenic activity (levonorgestrol and norethisterone) and those which do not - the former group having lower risk of VTE and IHD, but less of the beneficial effects of oestrogens on hair and skin.

Risk of venous thromboembolism

Risk of VTE per 100 000 women per year:

  • 5-10 in healthy non-pregnant women
  • 15 in women taking second-generation OCP, e.g. levonorgestrol, or third-generation OCP with drospirenone
  • 25 in women taking third-generation OCP with desogestrel or gestodene
  • 60 in pregnant women
  • 100 in women aged >39 taking OCP

Risk is increased during travel involving long periods of immobility (over 5 hours).

Risk factors for venous thromboembolism

Use with caution if any of following factors present but avoid if two or more factors present:

  • FH of VTE in first-degree relative <45 years (avoid desogestrel or gestodene, or if known prothrombotic coagulation abnormality e.g. factor V Leiden, antiphospholipid antibodies or or lupus anticoagulant);
  • obesity - BMI >30 (avoid if BMI >39);
  • long-term immobilisation e.g. in wheelchair (avoid if bedbound or leg in plaster cast);
  • history of superficial thrombophlebitis;
  • age over 35 years (avoid if over 50 years);
  • smoking.

Risk factors for arterial disease

Use with caution if any one of following factors present but avoid if two or more factors present:

  • FH of arterial disease in first degree relative aged under 45 years (avoid if atherogenic lipid profile);
  • diabetes mellitus (avoid if diabetes complications present);
  • hypertension - blood pressure >140/90 (avoid if >160/95);
  • smoking (avoid if 40+ cigarettes daily);
  • age >35 years (avoid if >50 years);
  • obesity (avoid if body mass index >39 kg/m2);

Migraine

Contra-indicated in:

  • migraine with typical focal aura;
  • migraine regularly lasting over 72 hours despite treatment;
  • migraine treated with ergot derivatives.

Use with caution in:

  • migraine without focal aura;
  • migraine controlled with 5HT1 agonist.

Interactions

  • Effectiveness reduced by hepatic enzyme inducers (e.g. carbamazepine, griseofulvin, modafinil, nelfinavir, nevirapine, oxcarbazepine, phenytoin, phenobarbital, primidone, ritonavir, St John's Wort, topiramate, and, above all, rifabutin and rifampicin).
  • For a short course, adjust OCP to provide ethinylestradiol 50µg or more daily; additional precautions needed whilst taking the drug and 4 weeks after. Consider an alternative if enzyme-inducing drug required long-term - see BNF 7.3.1.
  • Rifampicin and rifabutin are so potent that alternative contraception is always required, for 4-8 weeks after stopping.
  • Some antibacterials (e.g. ampicillin, doxycycline) impair bacterial flora. Additional precautions should be taken with a short course, and for 7 days after. If the course exceeds 3 weeks, the bacterial flora develop resistance and precautions become unnecessary unless a new antibacterial is prescribed.

Surgery

  • stop oestrogen-containing contraceptives 4 weeks before major surgery (or involving prolonged immobilisation of a leg)
  • depot progestogen-only contraceptive may be used temporarily;
  • if contraceptive cannot be stopped, thromboprophylaxis with heparin and TEDS is advised.

Reasons to stop immediately

Combined contraceptives or HRT should be stopped if any of the following occur:

  • sudden severe chest pain;
  • sudden breathlessness (or haemoptysis);
  • unexplained unilateral calf swelling or pain;
  • severe stomach pain;
  • serious neurological effects, including: headache; sudden loss of vision, hearing, or other perceptual disorders; dysphasia; collapse or first unexplained seizure or weakness; motor disturbance; marked numbness;
  • hepatitis, jaundice, liver enlargement;
  • blood pressure > 160/95 mmHg;
  • prolonged immobility after surgery or leg injury;
  • detection of a risk factor which contra-indicates treatment

Cancer

Breast cancer risk may be increased in women taking the combined OCP, but there are also a number of reassuring studies. Higher diagnosis rates may be due to earlier diagnosis. The most important factor appears to be the age at which the contraceptive is stopped rather than duration of use; any increase diagnosis rate diminishes during the 10 years after stopping and disappears by 10 years.

Cervical cancer risk may be slightly increased with use of combined OCPs for 5 years or longer; the risk diminishes after stopping and disappears by about 10 years. The risk of cervical cancer with transdermal patches is not yet known.

Ovarian and endometrial cancer risks are reduced by about 50% in women taking low-oestrogen combined OCPs. Colorectal cancer may be reduced by 20%.

The possible small increase in the risk of breast cancer and cervical cancer should be weighed against the protective effect against cancers of the ovary and endometrium.

Female reproductive cycle

Click for diagram of female reproductive cycle.

BRAND OESTROGEN (µg) PROGESTOGEN (µg) NOTES
Combined oral low strength
Loestrin 20 Ethinylestradiol 20 Norethisterone 1 2nd generation
Mercilon Ethinylestradiol 20 Desogestrel 150 3rd generation
Yaz Ethinylestradiol 20 Drospirenone 3000 3rd generation
Femodette Ethinylestradiol 20 Gestodene 75 3rd generation
Sunya 20/75 Ethinylestradiol 20 Gestodene 75 3rd generation
Combined transdermal low strength
Evra Ethinylestradiol 20 Norelgestromin 150 3rd generation
Combined oral standard strength
Logynon and ED Ethinylestradiol 30-40 Levonorgestrel 50-125 2nd generation
Microgynon 30 and ED Ethinylestradiol 30 Levonorgestrel 150 2nd generation
Ovranette Ethinylestradiol 30 Levonorgestrel 150 3rd generation
BiNovum Ethinylestradiol 35 Norethisterone 500-1000 2nd generation
Brevinor Ethinylestradiol 35 Norethisterone 500 2nd generation
Loestrin 30 Ethinylestradiol 30 Norethisterone acetate 1500 2nd generation
Norimin Ethinylestradiol 35 Norethisterone 1000 2nd generation
Ovysmen Ethinylestradiol 35 Norethisterone 500 2nd generation
Synphase Ethinylestradiol 35 Norethisterone 500-1000 2nd generation
TriNovum Ethinylestradiol 35 Norethisterone 500-1000 2nd generation
Cilest Ethinylestradiol 35 Norgestimate 250 3rd generation
Marvelon Ethinylestradiol 30 Desogestrel 150 3rd generation
Yasmin Ethinylestradiol 30 Drospirenone 3000 3rd generation
Femodene and ED Ethinylestradiol 30 Gestodene 75 3rd generation
Katya 30/75 Ethinylestradiol 30 Gestodene 75 3rd generation
Triadene Ethinylestradiol 30-40 Gestodene 50-100 3rd generation
Norinyl-1 Mestranol 50 Norethisterone 1000 2nd generation
Progestogen-only oral
Cerazette Desogestrel 75 3rd generation
Femulen Etynodiol diacetate 500
Micronor Norethisterone 350 2nd generation
Norgeston Levonorgestrel 30 3rd generation
Noriday Norethisterone 350 2nd generation
Progestogen-only injections and implants
Depo-Provera Medroxyprogesterone acetate Prolonged action; may reduce BMD
Noristerat Norethisterone enantate Short-term use
Implanon Etonogestrel Up to 3 years efficacy
Progestogen-only intra-uterine device
Mirena Levonorgestrel



Oral progestogen-only hormonal contraceptives

Oral progestogen-only preparations may be suitable when oestrogens are contra-indicated (e.g. PMH of VTE, or FH or predisposition to VTE), but have a higher failure rate. They are suitable for older women, heavy smokers, and in hypertension, valvular heart disease, diabetes mellitus, and migraine. Menstrual irregularities are more common but tend to resolve on long-term treatment.

Mechanisms of action

  • Gonadotrophins: in one study, the magnitude of the LH peak was reduced by 75%, and was of shorter duration; FSH peak was non-existent.
  • Luteal activity: as defined by prog >10 nmo/L, was suppressed to 14% of cycles in implant users, rising to 54% by 5th year.
  • Follicular development: as assessed by USS and hormonal profiles, only 34% of cyles in implant users were ovulatory, and all with abnormal hormone profiles; further 13% had luteinization without follicular rupture. Presumably the various responses to LH-FSH surge are dissociated when the surge is of abnormal magnitude and duration.
  • Cervical mucus viscosity: anti-oestrogenic effects of progesterones greatly increases the cervical barrier. In one study, 90% of samples from controls permitted sperm migration >2cm, whereas most samples from implant users were too thick to be collected or aspirated up a capillary tube, and none permitted sperm migration >2cm.

Interactions

Progestogen-only OCPs are not affected by antibacterials that do not induce liver enzymes. Efficacy is reduced by enzyme-inducing drugs, so an alternative method is recommended during treatment with an enzyme-inducing drug and for at least 4 weeks after.

Surgery

All progestogen-only preparations are suitable before major elective surgery, including prolonged immobilisation of a lower limb.

Breast cancer

There is a small increase in the risk of breast cancer in women using, or who have recently used, a progestogen-only OCP; this may be due to an earlier diagnosis. The most important risk factor appears to be the age when it is stopped rather than duration of use; the risk disappears gradually over 10 years after stopping. The CSM has advised that a possible small increase in the risk of breast cancer should be weighed against the benefits.




Progestogen-only injected, implanted and intra-uterine contraceptives

Depo-Provera may reduce bone mineral density. Generally avoid in adolescents and women with osteoporosis or risk factors, and review use after 2 years.

Effectiveness of parenteral contraceptives is not affected by antibacterials. However, effectiveness of norethisterone and etonogestrel (but not MPA) may be reduced by enzyme-inducing drugs.

Mirena releases levonorgestrel directly into the uterine cavity. It is licensed as a contraceptive, for treatment of primary menorrhagia and for prevention of endometrial hyperplasia during oestrogen replacement. May be the method of choice for women with menorrhagia.

Effects of progestogen-only IUD are mainly local and hormonal including prevention of endometrial proliferation, thickening of cervical mucus, and suppression of ovulation in some women (in some cycles). The IUD itself may contribute slightly to the contraceptive effect. Return of fertility after removal is rapid and appears to be complete.

Advantages over copper IUDs are improvement in dysmenorrhoea and reduced blood loss; also evidence that PID may be reduced (particularly in the youngest age groups who are most at risk).

In primary menorrhagia, menstrual bleeding is reduced significantly within 3-6 months of insertion, probably because it prevents endometrial proliferation.