DES use as a postcoital contraceptive agent, 1970

Endometrial Carbonic Anhydrase After Diethylstilbestrol as a Postcoital Antifertility Agent

1970 Study Abstract

Others have shown that the oral administration of diethylstilbestrol 25 mg daily for 5 days is an effective postcoital antifertility method.

This dose of the estrogen was started in 4 volunteers on the day basal temperature rose.

Endometrial carbonic anhydrase, 5 days after the temperature rise, was lowered to an average of 9.8 enzyme units (EU)/g as compared to the average control value of 21.2 EU/g.

This decreased carbonic anhydrase activity may represent a barrier to implantation, although other antifertility mechanisms may also be activated by diethylstilbestrol.

Sources

  • Endometrial Carbonic Anhydrase After Diethylstilbestrol as a Postcoital Antifertility Agent, Obstetrics & Gynecology, greenjournal, September 1970.
  • Featured image credit Nicholas Gercken.
DES DIETHYLSTILBESTROL RESOURCES

Post-coital DES in large doses

DES use as a postcoital contraceptive agent is discussed

1972 Study Abstract

To study the contraceptive effective in human beings, large doses of estrogen were administered to 2000 women between 14 and 52 years of age.

In 1418 cases (71%) ethinyloestradiol (EO) was used, in 524 cases (26%) diethylstilbestrol (DS), and in 58 cases (3%) the estrogen administered was not recorded.

In 47.5% the unprotected coitus occurred between 12 and 16 days before the next expected menstruation, in 60.9% it occurred between 10 and 17 days, and in 9.6% (193 cases) the day of the cycle was not mentioned.

There were 14 pregnancies among the 2000 women. In only 3 cases did the pregnancy occur after 3 mg doses of EO or 30 mg DS started within 36 hours. No pregnancies occurred after 5 mg EO or 50 mg DS. In 3 cases the pregnancy could have been the result of a later unprotected coitus. In another 3 cases medication was started after more than 48 hours.

In cases of vomiting occurring within 1 hour after ingestion of a tablet, another tablet was given 30 minutes after an anti-emetic. If all tablets were vomited estradiol benzoate, 30 mg per day for 5 days, was injected. Other side effects were tender breasts, menorrhagia, headache, dizziness, abdominal pain, and amenorrhea. Changes in their cycle were reported by 662 women. Most stabalized after 1 cycle. Side effects prohibit this method for routine contraception but it could be valuable in special cases.

There is as yet no statistical proof of its degree of effectiveness. The method of action of these drugs is not certainly known.

Sources

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The “morning-after pill”

The use of diethylstilbestrol (DES) as a postcoital contraceptive agent is discussed

1971 Study Abstract

A course of post-coital estrogens, in adequate dosage, is a highly effective and safe (though misnamed) form of post-coital contraception that deserves to be more widely known and prescribed. Both unwanted pregnancies and the demand for abortion could be reduced by its widespread use in emergency situations.

Several natural and synthetic estrogens have been used in various dosages; a popular regimen is 5 milligrams of stilbestrol, 5 times per day for 5 days, preferably accompanied by an anti-emetic, since nausea and occasional vomiting may occur.

Some authorities advise starting the course of estrogens within 48 hours of unprotected intercourse and others set a reliable outside limit of 72 hours, turning a Friday night indiscretion into a Monday morning routine appointment rather than a weekend emergency.

For a series of 30 cases started on the above dosage within 72 hours of coitus without contraception or with condom failure, I am able to report no pregnancies. These patients proved particularly responsive to counselling, almost all keeping subsequent appointments for a more satisfactory method of birth control.

Similar success was reported verbally at the recent American College Health Association conference1 by a gynecologist from Yale.

An interim report from the University of Utrecht indicated no failures in 72 women using post-coital estrogens, and a comprehensive review of the literature on the subject, with an analysis of 1000 cases, is to be presented by the same author at the forthcoming Fertility-Sterility Conference in Tokyo in October.

Professor Haspels’ excellent paper should do much to clear up the confusion that exists in many minds between this highly reliable method of post-coital contraception and the virtually useless attempts that are sometimes made to terminate a pregnancy by administering estrogens after a missed menstrual period.

This subject is, of course, unrelated to the use of prostaglandins, which is an entirely different story.

Sources

  • The “morning-after pill”, Canadian Medical Association journal, NCBI PubMed PMC1931140, 1971 Aug 7.
DES DIETHYLSTILBESTROL RESOURCES

Postcoital contraception : present and future options

DES still used for emergency contraception in 1995

Abstract

PURPOSE
This article reviews information on currently available postcoital contraceptives, and discusses recent advances in postcoital contraception, mostly notably RU 486.

METHODS
Postcoital contraceptives, or “morning after pills,” are currently available in the form of high dose estrogens, oral contraceptives, danazol and intrauterine devices. These methods are plagued by high incidences of side effects and less than optimal success rates.

RESULTS
Currently, their primary use in the adolescent age group is for victims of sexual assault, but they may also be used as back-up for consensual unprotected intercourse. RU 486, best known as a first trimester abortifacient, has a number of potential uses, including that of a postcoital contraceptive. Two recently published studies from the UK showed RU 486 to have a very low pregnancy rate and fewer side effects when compared with current methods. RU 486 may someday replace high doses of oral contraceptives as the method of choice for postcoital contraception.

PIP
Postcoital contraceptives are available for adolescent use in the US. They include combination oral contraceptives (OCs), high dose estrogens, danazol, and IUDs. Mifepristone (RU-486) is currently not available in the US but is used in France, the UK, and Sweden. Postcoital contraception is especially important for adolescents who have a very high pregnancy rate due to poor contraceptive use. Administration of 2-5 mg ethinyl estradiol (EE) for 5 days beginning within 72 hours of unprotected intercourse yields pregnancy rates ranging from 0-0.92%. EE-related side effects include nausea, vomiting, sore breasts, and irregular menstrual bleeding. DES should not be used, since it is associated with reproductive tract anomalies and vaginal cancers in exposed offspring. Conjugated estrogens have not been used in adolescents for postcoital contraception. The Yuzpe regimen consists of 2 tablets of a combined OC with 200 mg EE and 2 mg dl-norgestrel administered within 72 hours of unprotected intercourse followed by the same dose 12 hours later. Common side effects are nausea and vomiting. Its pregnancy rate is 1.8%. Levonorgestrel-containing OCs can also be used. Administration of 800-1200 mg danazol up to 120 hours after unprotected intercourse protects against pregnancy in about 98% of cases. Copper IUDs have a high efficacy rate when used as postcoital contraception (99.9%), but public opinion, medicolegal considerations, financial costs, and potential for infection impede IUD as a postcoital contraceptive in the US. RU-486 is best known as an abortifacient. It is also a potential postcoital contraceptive. Two UK studies find that RU-486 used as a postcoital contraceptive has a very low pregnancy rate and fewer side effects than the Yuzpe regimen and danazol. It is much more costly than currently used postcoital contraceptives (600 mg of RU-486 cost US$ 68, while Ovral costs US$ 0.48-2.24). Nevertheless, RU-486 may replace the higher doses of OCs as a postcoital contraceptive method.

Sources

  • Postcoital contraception: present and future options, The Journal of adolescent health : official publication of the Society for Adolescent Medicine, NCBI PubMed PMID: 7742340, 1995 Jan.
DES DIETHYLSTILBESTROL RESOURCES

Emergency contraception : 1994 review

Diethylstilbestrol used as a “morning after” contraceptive

Abstract

In the Netherlands, many women use a postcoital method of contraception in “emergency” situations.

Postcoital contraception started in the 1960’s with the administration of large doses of estrogens: 50 mg diethylstilbestrol for 5 days or 5 mg ethinylestradiol for 5 days.

In the eighties, a double-blind study compared the original hormonal therapy of 5 mg ethinylestradiol for 5 days with a combination pill containing just 0.1 mg in combination with 1 mg d1-norgestrel, of which two doses are give, the second 12 hours after the first. This method was as effective in preventing pregnancy as the original treatment with high estrogen dosage. Moreover, it resulted in women suffering less nausea and vomiting. One study from Hong Kong indicated that levonorgestrel without ethinylestradiol was as effective as the combination. Postcoital use of an intrauterine device to prevent pregnancy can be used as an alternative to the hormonal method. A recent development is the use of an antiprogestagen pill: 600 mg Mifepristone on day 27 of the cycle; side effects are minimal and the success rate is high. Mifepristone should be registered and made available in all countries for this indication.

PIP

Many women in the Netherlands depend on a postcoital contraceptive (PCC) method in situations of unprotected intercourse. The incidence rate for abortions and for adolescent pregnancies in the Netherlands is the lowest worldwide. Dutch society matter-of-factly accepts adolescent sexuality and provides formal and informal sex education and readily accessible contraceptive services. Emergency contraception should be administered within 72 hours after unprotected intercourse (e.g., rape or incest) or mechanical contraceptive failure. Administration of 5 mg ethinyl estradiol (EE) for 5 days as a PCC first occurred in the Netherlands in 1964, and PCC usage peaked at 55,000 in 1975. Side effects of EE include, in order of frequency, nausea, vomiting, tender breasts, and menorrhagia. Possible modes of action for EE are more rapid transport of fertilized ova through the oviduct and slowed maturation of the endometrium, resulting in suppressed implantation. The Yuzpe PCC method involves 4 tablets of a combined oral contraceptive (each tablet with 50 mcg EE + 250 mcg levonorgestrel) administered within 72 hours followed by 2 tablets 12 hours later. Side effects are similar to those of EE alone, as is the effectiveness rate. A dose of 0.75 mg levonorgestrel alone is as effective at preventing pregnancy as the Yuzpe regimen. Side effects are considerably less common with the levonorgestrel regimen than the Yuzpe regimen. For women who present more than 72 hours after and less than 7 days after unprotected intercourse or for those with contraindications to estrogen, a copper-releasing IUD can serve as a PCC. A postcoital IUD can cause serious complications for women with a sexually transmitted disease, however. Taking RU-486 during the luteal phase of the menstrual cycle greatly drops plasma levels of progesterone and estradiol. Postovulatory administration of an antiprogestogen is the best PCC method because of minimal side effects and a high success rate.

Sources

DES DIETHYLSTILBESTROL RESOURCES

Postcoital contraception underrecognized and underutilized

Diethylstilbestrol as a “morning after” contraceptive

1992 Study Abstract

Postcoital contraception can play an important role in the prevention of unwanted adolescent pregnancy in the US.

Diethylstilbestrol (DES), 25 mg twice daily for 5 days within 24 to a maximum of 72 hours after unprotected sexual intercourse, received US Food and Drug Administration (FDA) approval for pregnancy prevention in 1973.

In 1978, however, the manufacturer, Eli Lilly, included in its packaging instructions that DES should not be used for postcoital contraception given the development of clear-cell adenocarcinoma of the vagina or cervix in the daughters of women who took DES to prevent spontaneous abortion.

The FDA had not withdrawn its approval of DES for this purpose. Other drugs that have been effectively used for postcoital contraception include 0.5 mg of norgestrel and 0.05 mg of ethinyl estradiol (2 tablets within 72 hours of unprotected intercourse and another 2 tablets 12 hours later) and conjugated estrogens.

This approach to pregnancy prevention sidesteps many of the medical and moral complexities associated with use of the abortifacient RU-486. In fact, the Catholic bishops of Great Britain have approved the use of postcoital contraception in women who are victims of sexual assault.

Sources

  • Postcoital contraception underrecognized and underutilized, Female Patient, NCBI PubMed PMID: 12287765, 1992 Jun.
  • Featured image bunchfamily.
DES DIETHYLSTILBESTROL RESOURCES

Post-coital contraception

In the 1960s and 1970s, high doses of DiEthylStilbestrol were used as post-coital contraception ; the morning-after pill

1985 Study Abstract

Current interceptive methods of contraception utilizable between ovulation and nidation include hormonal methods and IUDs. Since the 1st clinical study of the use of high doses of estrogen as a postcoital contraceptive appeared in 1967, the remarkable efficacy of the method has been confirmed by numerous other studies.

The most important series used 50 mg diethylstilbestrol (DES) or 5 mg ethinyl estradiol (EE) per day for 5 days beginning within 72 hours of unprotected intercourse. The mechanism by which estrogens exercise their interception are unclear, but there are probably several factors involved including luteolysis and anomalies in endometrial development. The method is highly effective but rates of nausea, vomiting, breast tenderness, and to a lesser degree menorrhagia are high. The incidence of extrauterine pregnancy is about 1 per 10 intrauterine pregnancies for any postcoital method. Estrogen postcoital contraception is preferable to DES because of the fear of genital adenosis or vaginal adenocarcinoma in case of failure of DES. Opinion is divided as to the teratogenic risks of high doses of estrogens in general.

Postcoital contraception with a progestin, levonorgestrel, which renders the endometrium inhospitable to nidation, was 1st described in 1973. The efficacy of norgestrel alone depends on the dose used. The most common secondary effects are spotting and cycle shortening. The method has the advantage of requiring a very small dose, but the disadvantage of requiring administration in the 12 hours following intercourse. Several combinations of estrogens and progestins have been proposed for postcoital use, of which the most interesting consists of 1 mg of dl-norgestrel and 100 mcg of EE repeated exactly 12 hours later. The treatment should be administered within 12 hours of unprotected intercourse. A multicenter study of 692 women treated with this method gave a pregnancy rate of 1.6%, which would have been lower if 4 women not meeting the conditions of treatment had been excluded. 52.7% of women treated had nausea or vomiting. Compared to estrogens alone, the EE-Norgestrel combination takes less time, requires 4 pills instead of 50 or 60, is better tolerated overall, and requires much less estrogen.

Postcoital insertion of an IUD is very effective and has the advantages that it can be used later than 72 hours following intercourse, it is the only method currently available in case OCs are contraindicated, it allows subsequent longterm effective contraception, and it is 100% effective. The major disadvantages are pain on periovulatory or postovulatory insertion and the risk of infection. Possible future hormonal methods of postcoital contraception based on use of anti-progesterone steroids, especially RU486, or of luteinizing hormone releasing hormone agonist are currently under development.

Sources

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Postcoital contraceptive

In 1973, the FDA considered DES safe as ‘morning-after’ pill

1983 Study Abstract

Postcoital contraceptives, the so-called “morning after pill,” are agents used as emergency treatment to prevent pregnancy after unprotected intercourse or contraceptive accidents.

In the 1960s and early 1970s high doses of estrogens were used in 5-day courses such as diethylstilbestrol 25-50 mg a day or ethinyl estradiol 0.5-5 mg a day begun within 72 hours after coitus. Although effective, a considerable drawback of the associated nausea and vomiting as well as an increased risk of menstrual disturbance during the treatment cycle.

Norgestrel alone in various dosages has been used postcoitally.

Quingestanol has been used as a continuing postcoital agent in Latin America but proved unacceptable owing to nausea and irregular bleeding.

In China “visiting pills” have been devised containing anordrin. In the West regimens of this sort have been superseded by the Yuzpe treatment of 100 mcg ethinylestradiol and 0.5 mg levonorgestrel initially, repeated after precisely 12 hours. The treatment must be initiated within 72 hours of exposure.

Postcoital contraceptives act by combinations of mechanisms–the function of the corpus luteum is disrupted, tubal motility may be affected, and changes in endometrial biochemistry prevent ovoimplantation. In a multicenter trial involving 602 women Yuzpe reported a pregnancy rate of 1.6%. Other workers show comparable figures of 0-3%. The primary side effects of the current hormonal method are nausea, which occurs in 61% of cases, and vomiting, 20% of cases. Both are mild and of short duration.

All postcoital methods carry a risk of ectopic pregnancy should the treatment fail. 3 ectopic pregnancies were recorded with diethylstilbestrol and 1 recently with the Yuzpe regimen. There have been no reports of thromboembolic complications.

If a hormonal form of postcoital treatment fails, the theoretical possibility of the pregnancy being harmed cannot be ruled out. The patient needs to be counseled about this, and careful records should be kept. Also important is the taking of an accurate menstrual and coital history to exclude exposures earlier in the menstrual cycle.

Lippes and coworkers showed the efficacy of copper IUDs as postcoital agents. These can be used up to 5 days from intercourse. An IUD is preferred if hormones are contraindictated, if exposure was more than 72 hours beforehand, if the woman desires the most effective method, and if she wants the IUD for longterm contraception.

Postcoital contraception, however defined, raises ethical questions. Postcoital methods could be classed as contraceptive rather than abortive within the maximum period (defined by medical scientific consensus) that may elapse between intercourse and nidation.

Sources

DES DIETHYLSTILBESTROL RESOURCES

Physician notes hazards of DES use to prevent pregnancy

Despite growing controversy surrounding its use as a “morning after pill,” diethylstilbestrol (DES) is prescribed liberally for rape victims

1978 Paper Abstract

Diamond questions the use of DES (Diethylstilbestrol) as a method of pregnancy prevention after rape because of

  • the increased risks of vaginal cancer in women exposed to DES in vitro;
  • the relationship to congenital anomalies and to endometrial carcinoma;
  • and the actual number of pregnancies resulting from rape.

According to Diamond, studies have shown that an insignificant number of pregnancies occur because of rape and to support this claim he cites a study conducted in Minnesota where 4,000 rapes resulted in 0 pregnancies. Diamond also assails the Catholic health care institutions which permit the use of DES as a postcoital contraceptive claiming that they are in actuality performing early abortion by medication.

Sources

  • Physician notes hazards of DES use to prevent pregnancy, Hospital progress, NCBI PubMed PMID: 631811, 1978 Mar.
  • Featured image lighthouseprc.
DES DIETHYLSTILBESTROL RESOURCES