Estrogens, Conjugated in Pregnancy and Breastfeeding

Risk Factor: XM
Class: Hormones / Estrogens

Contents of this page:
Fetal Risk Summary
Breast Feeding Summary
Questions and Answers

Fetal Risk Summary

Conjugated estrogens are a mixture of estrogenic substances (primarily estrone). The Collaborative Perinatal Project monitored 13 mother-child pairs who were exposed to conjugated estrogens during the 1st trimester (1, pp. 389, 391). An increased risk for malformations was found, although identification of the malformations was not provided. Estrogenic agents as a group were monitored in 614 mother-child pairs. An increase in the expected frequency of cardiovascular defects, eye and ear anomalies, and Down's syndrome was reported (1, p. 395). Reevaluation of these data in terms of timing of exposure, vaginal bleeding in early pregnancy, and previous maternal obstetric history, however, failed to support an association between estrogens and cardiac malformations (2).

An earlier study also failed to find any relationship with nongenital malformations (3). No adverse effects were observed in one infant exposed during the 1st trimester to conjugated estrogens (4). However, in an infant exposed during the 4th7th weeks of gestation to conjugated estrogens, multiple anomalies were found: cleft palate, micrognathia, wormian bones, heart defect, dislocated hips, absent tibiae, bowed fibulae, polydactyly, and abnormal dermal patterns (5). Multiple other agents were also taken during this pregnancy, but only conjugated estrogens and prochlorperazine (see also Prochlorperazine) appeared to have been taken during the critical period for the malformations.

Conjugated estrogens have been used to induce ovulation in anovulatory women (6). They have also been used as partially successful contraceptives when given within 72 hours of unprotected, midcycle coitus (7). No fetal adverse effects were mentioned in either of these reports.

Breast Feeding Summary

No reports of adverse effects from conjugated estrogens in the nursing infant have been located. It is possible that decreased milk volume and decreased nitrogen and protein content could occur (see Mestranol, Ethinyl Estradiol).


  1. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA:Publishing Sciences Group, 1977.
  2. Wiseman RA, Dodds-Smith IC. Cardiovascular birth defects and antenatal exposure to female sex hormones: a reevaluation of some base data. Teratology 1984;30:35970.
  3. Wilson JG, Brent RL. Are female sex hormones teratogenic? Am J Obstet Gynecol 1981;141:56780.
  4. Hagler S, Schultz A, Hankin H, Kunstadter RH. Fetal effects of steroid therapy during pregnancy. Am J Dis Child 1963;106:58690.
  5. Ho CK, Kaufman RL, McAlister WH. Congenital malformations. Cleft palate, congenital heart disease, absent tibiae, and polydactyly. Am J Dis Child 1975;129:7146.
  6. Price R. Pregnancies using conjugated oestrogen therapy. Med J Aust 1980;2:3412.
  7. Dixon GW, Schlesselman JJ, Ory HW, Blye RP. Ethinyl estradiol and conjugated estrogens as postcoital contraceptives. JAMA 1980;244:13369.

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Questions and Answers

Why has conjugated estrogen never come out in a generic form?, I have been taking it for twenty years now and it is still very expensive, even with my co-pay. I realize HRT is very controversial. Does that have something to do with it?

Good question and I assume that you are referring to Premarin® (conjugated estrogen). HRT controversy really has nothing to do with a lack of generic. The real reason is that Wyeth (the manufacturer) got lucky with this one....and it has to do with the drug's composition.

Also, Wyeth still has one non-expired patent that protects Premarin (this type of patent is called an Orange Book patent). US Patent 5,210,081 does not expire until February 26, 2012. A generic company would have to circumvent or invalidate this patent if they wanted to launch a generic version of it.

Third, Wyeth had filed a Citizen's Petition (legal maneuver) to block the generics from launching a generic.

BTW, here is some history on Premarin:
Premarin is extracted from pregnant mare urine (hence the name). Reliable estimates indicate there are now at least 50,000 production mares on dedicated farms in N. America (mostly located in Canada).

Premarin contains a number of different estrogens. Precisely how each of these various estrogens contribute to the drug's overall effectiveness has not been definitively determined -- and is the real reason for the lack of generics. Premarin's approval in 1942 predated the current requirements for such comprehensive analysis of products under review for marketing approval.

Previously it was thought that two estrogens were the sole active ingredients in Premarin. Newer laboratory and clinical studies show this may not be the case. Rather, other components in Premarin may contribute to the drug's effectiveness.

Although this finding does not prove that the DHES in Premarin has an important therapeutic effect, "it underscores the lack of precise knowledge of the makeup of Premarin and the relative importance of its components, and therefore the lack of a standard on which to evaluate a generic copy."

In November 1994, Wyeth filed a citizen petition requesting that DHES be reclassified as a concomitant component. The firm maintained that the compound contributes to the drug's potency, and therefore, effectiveness, and further requested that FDA require the compound to be included in any generic copies of the drug.

Esterified VS Conjugated Estrogen-What is the difference?, I have scoured the Internet and have not been able to find the answer to this...can anyone tell me if Estratest HS contains components from the same compound Premarin with added testosterone is made from? I haven't been able to find out what is in this drug. Is it natural or is it made from the hormones derived from pregnant mares?

I believe that both are combination estrogens, but Conjugated are all natural estrogens, and Esterfied are combinations of synthetic estrogens. Sometimes one will work better with a particular menopausal or post menopausal symptom or problem.

Why no stocks of Premarin Conjugated estrogen by WYETH in drugstores for months now?,


What are the odds of not taking my estrogen hormone?, Im 41 years old and recently went through a Total Histerectomy. (no cancer). The doctor prescribed an estrogen conjugated hormone but I really wont like to be taking medications for the rest of my life. My husband and I have known of risks associated with hormones, however, Im concerned if not taking it would affect my feminine features, say voice, breast, unwanted hair (masculine features). Anybody knows about it? some doctors are kind of quiet about this.

One thing I can say for sure, is that taking HRT (hormone replacement therapy) puts so many women at an extremely high risk for DVT's and/or PE's (deep vein thrombosis, pulmonary embolism; blood clots, clots that embolize to the lungs). Many women chose not to take it due to the high risks, you're not alone. Unfortunately, most people that chose not to continue on taking HRT's of any kind can be found on a yahoo forum for DVT's and/or PE's. They've already found out the hard way.

Here's a good site to read up on the causes and symptoms of DVT's & PE's

I hope this helps!

conjugated estrogen cream?, My doc prescribed this cream. Can it cause hotflashes?

Generally not, because the medicine is used topically and should not be very well systemically absorbed. This medicine is primarily used to treat local symptoms of menopause or low estrogen levels.

I would think the biggest side effect to worry about would be burning/stinging if the skin is broken.

If you are using it for menopause, though, hot flashes as a symptom of menopause probably won't be treated, so they may continue- but they would be a symptom of menopause, and not a side effect of the cream.

Does conjugated equine (horse) estrogen use for breast enlargement in men such as Premarin work.?, Premarin is a very complex and estrone is weaker by far than estradiol in its ability to stimulate breast tissue. In fact this particular estrogen can even be given to men, since it has no feminizing properties (Washburn 1996). Some women who have tried both Estrace and Premarin, or the patch and Premarin, decide that they like Premarin better because there is less breast tenderness, whereas pure estradiol feels "too strong." Can we conclude that estrone is better or is Estradiol more effective and popular?

My medical knowledge is limited in that area.


My wife takes 8 conjugated estrogen(0.626)tablest. Should she take soy menopause(herbal)instead?,

This is something your wife needs to discuss with her doctor. There is no right or wrong as to whether to take estrogen or not. This has to be a decision the patient and doctor make together.