10.1 Oral contraceptives

The background rate of spontaneous VTE in healthy women who are not pregnant and who do not use the combined oral contraceptive (COC) pill is around five cases per 100,000 women per year. The risk is increased threefold (15/100,000 women per year) in users of second generation contraceptives,¹⁹⁰ and six fold (30/100,000 women per year) in users of third generation oral contraceptives (i.e. containing desogestrel or gestodene).¹⁹¹

The absolute risk of thrombosis in women taking third generation pills is small (an excess risk of 10-25 cases of VTE per 100,000 women years) and is less than the risk associated with pregnancy (estimated at 100 cases per 100,000 maternities). However, the risks are higher during the first year of use, approaching 30 per 100,000 women per year for users of third generation COC.¹⁹² The risk is also much higher in women with thrombophilias.¹⁹²

10.1.1 COMBINED ORAL CONTRACEPTIVES AND SURGERY

Whether or not to stop the combined oral contraceptive pill before major surgery is a controversial issue. The risk of postoperative VTE increases from 0.5% to 1% for pill users versus non-users.¹⁹³ This small absolute excess risk in COC users must be balanced against the risks of stopping the pill 4-6 weeks prior to surgery, including unwanted pregnancy, the effects of surgery and anaesthesia on a pregnancy, and the risks of a subsequent termination. These risks should be communicated to the patient and, if it is agreed to stop COC, adequate alternative contraception should be arranged until COC are restarted. The timing of restarting COC will involve individual assessment, e.g. postoperative complications or immobility. Each case should be judged according the patient's additional risk factors for VTE (see Table 1) and their contraceptive preferences. When considering perioperative prophylaxis in current (or recent) pill users, each case should be judged according to additional risk factors. In emergency surgery, routine VTE prophylaxis should be given as the risk of VTE is greater.

10.1.2 PROGESTOGEN-ONLY CONTRACEPTIVES

There is no evidence that low doses of progestogens used for contraception are associated with increased risk of VTE. They may be substituted for COC in women with previous VTE or who are at high risk of VTE.⁶¹ There is no evidence that such preparations should be stopped prior to elective surgery.

However, there is evidence of an association of VTE risk with higher doses of progestogen used for other therapeutic indications (e.g. menstrual disorders), with a five to sixfold increase in the risk of VTE.^194,195

10.2 Hormone replacement therapy and raloxifene

Recent studies have shown that, like COCs, oral oestrogen-containing hormone replacement therapy (HRT), and the selective oestrogen receptor modulator, raloxifene ¹⁹⁶ also increase the risk of VTE threefold, especially in the first year of use. This translates to an absolute risk of 30 per 100,000 women per year for users of HRT compared to 10 per 100,000 women per year for non-users. The risk is increased by obesity and in the presence of thrombophilias^197,198 and is 10-fold higher in older women (mean age 67 years) with coronary heart disease.¹⁹⁹ It is not yet established if HRT is also a risk factor for postoperative VTE,¹⁹⁸ however most HRT users will merit routine prophylaxis (as age over 40 is an independent risk factor: see Table 1).

In patients with a personal history of VTE, an RCT of oral HRT observed a high risk of recurrence, especially in patients with thrombophilias.^200,201 Such women who wish to continue HRT should be referred to a centre or specialist with expertise in thrombophilia; as should women with no personal history of VTE but where thrombophilia is identified through screening. Transdermal HRT may be preferred in such women because it has a lesser effect on haemostasis compared to oral HRT.²⁰²

Women starting COC, higher dose progestogens, oral HRT or raloxifene should be advised of the small absolute increased risk of VTE. They should have a personal and family history taken of VTE and of additional risk factors for thromboembolic disease (e.g. obesity: see Table 1).

A personal history of VTE is a contraindication to the use of COC and oral HRT.

A history of VTE in a first degree family member is a relative contraindication to use of COC, higher dose progestogens, oral HRT or raloxifene, irrespective of the results of thrombophilia screening.

In current (or recent) COC, higher dose progestogen, HRT or raloxifene users who are undergoing surgery, it is recommended that medical practitioners: discuss the balance of risks and benefits with the patient when considering stopping these hormones prior to elective surgery arrange adequate alternative contraception if COC is to be discontinued consider specific antithrombotic prophylaxis according to overall risk factors (see Table 1) give VTE prophylaxis routinely in emergency surgery.