Delayed adverse effects of contraceptives

DES used as an emergency contraception, Hungary, 1978

Abstract

It is almost impossible at this point to make an estimate of the possible delayed adverse effects of the hormonal contraceptives presently marketed. The consequences of the administration of DES were revealed years later as it affected the children of the women who had been taking it.

The author discusses the word “catastrophy” in connection with this kind of consequences. He asks the question whether the mortality due to illegal abortion and even to legal abortion in the 1st years following its legalization should not also be considered as a catastrophy. The author refers in his argument to a paper published in the journal Orvosi Hetilap by Professor Csaba in 1977.

Another question doctors ask themselves concerns the relativity of a side-effect’s seriousness. Should one consider the damage done to the individual, or the number of subjects affected? There is no doubt that the presently used hormonal contraceptives contain a number of possible side effects, which however may be kept under control to a certain extent by doctors who carefully respect their indications and contraindications before prescribing them. But it is at this point extremely difficult to predict which delayed effects they might have. The medical schools in Hungary are doing a lot of research on the subject, but what can be done about the women who have been taking oral contraceptives for 10 years already? The possible delayed effects have not even started to show in these patients.

The author underlines the fact that medical schools should insist more than they do on the ethical aspects of medicine.

Sources

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Postcoital contraceptives in clinical practice

DES used as an emergency contraception, Czechoslovakia, 1977

Abstract

55 women were administered a series of postcoital contraceptives, 35 of whom received only a single application and 20 received the preparations for more than 1 cycle (more than 2 but less than 13).

34 women of the 1st group (48 hours after unprotected coitus) and 7 women from the 2nd group were administered diethylstilbestrol (DES) for 5 days for a total of 250 mg.

The remaining subjects were given norethisterone Spofa for 3 days at 30 mg/day.

Results from this administration in the sense of a general contraceptive were not considered favorable, primarily due to contraindications in regard to physiological side effects, particularly with DES. DES proved to be the most successful in preventing pregnancy.

Sources

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The “Morning-After Pill”

Abstract from “Quiz the Expert” dealing with current advances or concerns in the field of fertility and sterility, 1977

The use of drugs for postcoital or “morning-after” contraception has been plagued with many controversies.

The most frequently used agent (and the only drug presently approved by the Food and Drug Administration [FDA] ) is diethylstilbestrol (DES).

The usual dosage is 25 mg twice a day for 5 days. If given soon after intercourse, the medication is found to be almost universally effective in the prevention of pregnancy.

However, at the same time DES was being approved as a contraceptive, its teratogenic effect on the unborn fetus was beginning to be realized. The association between DES exposure and the late development of clear cell adenocarcinoma of the vagina and cervix is now well known. Although DES is still approved as a postcoital contraceptive, the FDA does require that the recipient be warned of the possible effects on the fetus should pregnancy occur.

Sources

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DES Use for Postcoital Contraception

DES also used as an emergency contraceptive in The United Kingdom, 1973

Summary

Oestrogens as postcoital contraception have been prescribed for 282 women at the Brook Advisory Centre (Avon) since January 1973.

A daily dose of 50 mg diethylstilboestrol for 5 days started within 72 hr of unprotected intercourse was used from January 1973. This was changed to 5 mg ethinyl oestradiol in May 1974.

There were no pregnancies nor any serious side effects. Follow-up showed that most women had their next period at the expected time.

Sources

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Our experience with “morning-after-pill”

DES used as an emergency contraception, Czechoslovakia, 1976

Abstract

37 women, 18-45 years old, were administered diethylstilbestrol (DES), 20 mg 3 times daily over the course of 5 days 24-48 hours after unprotected intercourse during the estimated time of ovulation.

Pregnancy was registered in only 1 case.

The effects of DES on the levels of follicle stimulating hormone, luteinizing hormone (LH), and progesterone were determined in 7 of these women during the entire course of a cycle.

  • A decrease in the level of LH was the only abberation found in comparison with a normal control group.
  • Ovulation was not suppressed by the application of DES.
  • Progesterone values in the luteal phase were normal for 4 women, while 3 showed a more rapid decrease in this level, which preceded menstruation by 3-5 days.
  • It was observed that after the administration of DES luteolysis did not occur in the ovulatory phase, although the ovulatory mechanism was disrupted.

Sources

  • Our experience with “morning-after-pill” (author’s transl), NCBI PubMed, PMID: 975286, 1976 Aug.
  • Image credit bob milton.
DES DIETHYLSTILBESTROL RESOURCES

Are oral contraceptives and DES involved in sex-linked cancer ?

Diethylstilbestrol as Post-Coital Contraceptive

1976 Abstract

The administration of large doses of estrogen to women shortly after unprotected, isolated coitus is followed by an extremely low incidence of pregnancy, suggesting an effect of the estrogen in preventing some aspect of early gestation. Controlled studies have not.been carried out, but there would seem to be little doubt of the efficacy of DES while lesser data on EE and other estrogens are suggestive.

The mode-of-action of the estrogens is not well established. Edgren cited the similarity between this human use and the tubal effects in animals (low dose acceleration of egg transport and high dose inhibition, tubal lock, in some species). In contradistinction, Dr. Hertz insisted that the anti-fertility effect in humans resulted from biochemical changes in the endometrium that precluded nidation. The review of Blye mentions both possibilities, as well as others.

The possible danger of this type of therapy, at least with respect to cancer, was disposed of rapidly by the panel. The postcoital use of estrogens, and particularly DES, is high-dose, short term therapy, quite different from the high-dose, long-term approach usually associated with carcinogenesis. Therefore, danger to the woman taking an estrogen correctly would seem minimal. Further, danger for the fetus seems of little significance, even if DES is conclusively proved to be carcinogenic. If pregnancy is prevented, no danger can exist; however, later abortion should be recommended in the event of an unsuccessful termination.

Sources

  • Are Oral Contraceptives and Diethylstilbestrol (DES) Involved in Sex-Linked Cancer?, Steroid Hormone Action and Cancer, PDF, 5.48 MB, 1976.
  • Image credit medium.
DES DIETHYLSTILBESTROL RESOURCES

DES still prescribed as oral contraceptive in 1975

American journal of obstetrics and gynecology

Abstract

The development of oral contraceptives (OCs) is briefly discussed.

From reviewing the literature it was seen that the 1st “OC” was the harmless, nontoxic, safe, and very inexpensive synthetic estrogen diethylstilbestrol, or stilbestrol, which is still the best OC in 1975.

This OC is still prescribed because a toxic dose, even up to 300,000 mg yearly, has never been encountered. The regimen consists of 3-5 mg daily for 26 nights with 3-5 nights shipped, plus a potent B-complex vitamin (Livitamin) 2-3 times daily.

This OC is unique in that ovulation and menstrual flow can be inhibited for 60-120 days. The patient can miss from 7-14 days before ovulation occurs, after 1 course of this OC. This regimen provides a harmless, nontoxic, and 100% effective OC.

Sources

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DES as an emergency contraception

Copper IUD, inserted after coitus averts pregnancy and provides continuing contraceptive protection

1975 Study Abstract

No pregnancies have been reported for 97 women treated postcoitally with the copper-T IUD. This method avoids the use of massive doses of estrogen with its associated side effects and provides continuing contraception.

The T-Cu has been found to be easy to insert in nulliparous women, with most patients being high school and college students.

Rape victims were 7% of the total. About half were treated within 24 hours of unprotected coitus. In 2 cases delay was 65 days. The majority of those seeking help did so during the fertile phase of the cycle. Sperm were found in the cervical mucus or vaginal secretions of 18 of the women. It has been estimated that a single unprotected intercourse at random throughout the cycle has a 2-4% risk of pregnancy. It was pointed out by a critic of the method that if a gonorrheal infection or pelvic inflammatory disease were present, serious complications might result. Also, serious infection might result if the patient was already pregnant from prior exposure.

Others reported results of their experiences with diethylstilbestrol (DES) as an emergency method. There were 3 failures in a reported group of 124 patients. Of these 2 had had more than 1 unprotected exposure and 1 had not taken the full 5-day course of therapy. In the total group of 124 patients, 50% had nausea and vomiting. Anxiety and depression were frequently present at a 2-week follow-up among DES patients. Only 15% refused offers of further contraception; 60% chose the pill or IUD. Of the 124 women in the DES group, 22 had had previous abortions and 4 subsequently returned for another course of DES therapy.

Sources

  • Copper IUD, inserted after coitus averts pregnancy and provides continuing contraceptive protection, International family planning digest, NCBI PubMed, PMID: 12307393, 1975 Sept.
  • Image credit pharmhealth.
DES DIETHYLSTILBESTROL RESOURCES

Total health needs of the rape victim

DES in the Treatment of Rape Victims

Prevention of Pregnancy, 1975

Post-coital prevention of pregnancy should be attempted in victims of childbearing age who are likely to be fertile, who are at a vulnerable time in their menstrual cycle, and who do not have contraceptive protection. Diethylstilbestrol, 25 mg orally twice daily for five days is prescribed. Because nausea is a frequent side effect, an antiemetic is of benefit prophylactically.

Abstract

The patient was also given a prescription for diethylstilbestrol (DES) to prevent pregnancy. It is an interesting historical note that this medication, experimentally effective in preventing pregnancy in laboratory animals, received its first human trial among rape victims. Kuchera2 administered DES within 72 hours of unprotected intercourse in 1,000 women at the University of Michigan Health Center. There were no pregnancies. This case illustrates the importance of disseminating health information to the public. This patient would never have come to our Emergency Room had she not been aware of the efficacy of DES.

MS. HILASKI

What are the side effects of DES and are we worried about subsequent vaginal adenocarcinoma in the victim’s female offspring should the victim become pregnant?

DR. KAUFMAN

First, the term “morning after pill” is a misnomer. Actually you must take 25 mg twice daily for five days. In light of the frequent nausea, some women do not complete the course and thus do have an increased risk of pregnancy. Nausea can be treated with an antiemetic such as prochlorperazine (Compazine®). Your point about vaginal adenocarcinoma in female offspring is well taken. While recent work has linked DES with higher than expected rates of vaginal adenocarcinoma in female offspring of the recipients of the drug, its actual occurrence is rare.3 Nevertheless, we customarily advise the victim that if she takes DES and becomes pregnant an abortion is indicated. DES is withheld if a menstrual history suggests the possibility of pregnancy prior to the assault, or if the victim is uncertain if she would have an abortion.

Sources

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Ectopic pregnancy after postcoital diethylstilbestrol

1975 Study Abstract

A case report is presented of the failure of diethylstilbestrol to prevent an ectopic pregnancy.

A 29-year-old physician’s wife, gravida 4, para 2, abortuses 2, received 25 mg diethylstilbestrol twice daily for 5 days beginning on Day 14 of the menstrual cycle after condom accident during intercourse the prior night. Withdrawal bleeding did not occur. The patient’s menstrual period before the condom accident had begun on August 25, 1971.

In mid-October she returned to the doctor feeling pregnant. The pregnancy test was positive on October 18, 1971, and physical examination revealed a soft uterus of about 7 weeks’ gestation.

Because of the fear of congenital defects in the fetus from diethylstilbestrol, suction curettage was carried out on October 27, 1971.

On October 31, 1971, the patient experienced great pain in the lower left quadrant. Her abdomen was tender and distended, and pelvic examination revealed a bulging cul-de-sac from which culdocentesis revealed nonclotting blood. Laparotomy revealed a ruptured tubal pregnancy on the left side. A left salpingectomy was carried out which pathologically confirmed a tubal pregnancy.

The question of whether diethylstilbestrol prevents implantation in the uterus but not in extrauterine sites is examined. A report by Morris is noted in which the only 3 pregnancies which followed diethylstilbestrol failure were ectopic. It is recommended that others with similar cases report them in order to better understand what occurs.

Sources

  • Ectopic pregnancy after postcoital diethylstilbestrol, American journal of obstetrics and gynecology, PMID: 1115139, 1975 Jan.
  • Image credit Asdrubal luna.
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