High-dose Diethylstilbestrol DES usage as a post-ovulatory pill
It has been known since the 1920s that high-dose oestrogens will prevent implantation and interrupt pregnancy in lower mammals. Following successful use in monkeys, Morris began conducting clinical trials in Yale in the 1960s. The first 100 cases were reported in 1967 (Morris and van Wagenen, 1967)] In these trials 25-50 mg stilboestrol (diethylstilbestrol USP) or 0.5-2.0 mg ethinyloestradiol were administered for five days to a group of carefully observed women with mid-cycle exposure to intercourse and both the presence of sperm in the vagina and a rise in basal body temperature confirmed; no pregnancies occurred.
To be effective, oestrogens must be administered within 72 hours of coitus since they work mainly by interfering with implantation. The exact mechanism remains to be established, but Haspels (1976) reported retarded hyperplasia in endometrial biopsies taken from women given high-dose oestrogens post-coitally, while Board (1970) reported a fall in endometrial carbonic anhydrase concentrations after post-coital oestrogens. There is also some evidence that ovum transport may be affected by high-dose oestrogens in some animal species (Smythe and Underwood, 1975), although there is no evidence for such an effect in humans. These findings have been used to explain the increased incidence of ectopic pregnancy apparent in some studies. Stilboestrol 25-50 mg, ethinyloestradiol 2-5 mg (normally 5 rag) and conjugated oestrogens 30 mg have all been used. All are administered for five days and must be given within 72 hours of intercourse.
The overall mean failure rate of all types of high-dose oestrogen is 0.7% (Fasoli et al, 1989). In 1973, Morris and van Wagenen reported 29 pregnancies in over 9000 mid-cycle exposures, only three of which were attributed to a true method failure. Van Santen and Haspels (1985) reported two pregnancies in 226 women in whom they calculated an expected rate of 11.9 pregnancies.
One case of acute pulmonary oedema during stilboestrol administration (Morris and van Wagenen, 1973) has been reported. Because of the possible association between the thromboembolic disorders and high-dose oestrogens, women with a history of thromboembolism are advised to avoid this form of PCC; however, no directly related incidents have been reported.
It is known that stilboestrol use during pregnancy is associated with an increased risk of vaginal adenosis and clear-cell carcinoma of the vagina and cervix in female offspring. There is no evidence that post-coital use of stilboestrol is associated with such an increased risk. Nevertheless, most clinicians now avoid using stilboestrol under any circumstances.
The common side-effects are those commonly associated with oestrogens. Most studies report nausea in around 50% of patients, mainly on day 1 of administration, and vomiting in up to 25%. These symptoms limit compliance and, if vomiting occurs, reduce efficacy. Up to 23% of women complain of breast tenderness and 11% of both menorrhagia and alteration in the timing of the next menstrual period. Vaginal spotting may occur during or shortly after treatment.
Morris and van Wagenen (1973) reported an increased incidence of ectopic pregnancy following high-dose oestrogens administered postcoitally. Three out of the 29 pregnancies that occurred were ectopic, a highly significant increase in the expected rate. For this reason a previous history of ectopic pregnancy is generally regarded as a contraindication to oestrogen-containing PCCs.
- Post-ovulatory contraception, Bailliere’s clinical obstetrics and gynaecology, PMID: 2225600, 1990 Jun.
- Image credit Maddie Photography.