Worse than thalidomide? The consequences of mass prenatal progestin exposure, 1950s-70s

by Jill Escher (Follow me on Twitter @autism_exposed)

When we think of prenatal drug disasters, we usually think of the sedative thalidomide, which caused horrific birth defects, and synthetic estrogen DES, which caused cancer and infertility in offspring, among other horrors.

Ignored, however, have been the downstream effects of the extensive use of progestin drugs in obstetric and fertility practice from the late 1950s through today. Progestins, not estrogens, were the most widely used anti-miscarriage drugs during several decades of practice that placed near-unquestioning faith in modern pharmaceuticals combined with near-nonexistent concern about impacts on the fetus.

These potent pseudo-hormones were given to countless millions of women who were deemed to be “at-risk” for miscarriage or who were termed “habitual aborters,” defined very liberally at the time as women who had suffered two or three prior miscarriages. The most common synthetic progestins administered in these protocols appear to have been Colprosterone, Delalutin, Deluteval, Norlutin Acetate, Provera, and Provest. (Reinisch and Karow, Prenatal Exposure to Synthetic Progestins and Estrogens: Effects on Human Development, Arch. Sex. Behav. 6:4 1977).

A 1969 medical text, “The Use of Progestins in Obstetrics and Gynecology,” by RW Kistner explained to physicians the then-standard of care for treatment of the “habitual aborters.” Please note the acute nature of the timing and dosage; the old practices resulted in massive fetal exposure to high doses of potent endocrine disrupting chemicals.

Provera: ... 10 mg daily, orally, during the first trimester of pregnancy; then 20 mg daily, orally, during the second trimester and 30 mg, daily, orally, during the third trimester.

Delalutin: (hydroxyprogesterone caproate) 375-500 mg (3-4 cc., intramuscularly) every week, starting as soon as pregnancy is confirmed and continuing to fetal viability.

Deluteval (hydroxyprogesterone caproate plus estradiol valerate): 500 mg. Delalutin plus 10 mg Delestrogen, intramuscularly, every week from the time of confirmation of pregnancy until fetal viability.”

If progesterone is administered, it is best started before conception and continued during pregnancy.... Progesterone, hydroxyprogesterone caproate and oral medroxyprogesterone acetate may be used in the prophylatic management of the habitual aborter.

Kistner, pp 112-13.

Nine years earlier, Dr. Edward Tyler, founder of the Tyler Medical Clinic in Los Angeles, had published his influential 1960 book, “Sterility: Office Management of the Infertile Couple,” (available online free at http://catalog.hathitrust.org/Record/001566807) which touted the use of the new synthetic hormones for a variety of fertility and other obstetric problems.

Dr. Tyler also endorsed large doses of synthetic progestins for miscarriage prevention:

A new injectable progestogen, 17a-hydroxyprogesterone caproate (17-AHPC) [note: this is Delalutin, which had been approved by the FDA for miscarriage prevention in 1956], differs from progestone in two major respects: large doses, for example, 250 mg per injection, can be given with relative freedom from local reactions; and, the therapeutic effect of each injection is prolonged so that a single injection produces progestational activity for 8 to 10 days. These qualities of prolonged action and relative freedom from local reactions make 17-AHPC a generally more desirable therapeutic agent than progesterone for intramuscular use, but dosage must be controlled carefully.

Sterility, pp. 253-56. Tyler's colleague, Dr. M Edward Davis, contributed a chapter concerning endocrine therapy for threatened miscarriage, explaining the theoretical basis for such intervention.

Progesterone is the pregnancy hormone and the logical substance to use in threatened abortion. If it can be demonstrated that the pregnancy is still viable, this hormone can be administered in moderately large doses. This key steroid may compensate for inadequate production of hormones by the corpus luteum or early chorion. Temporary supplementation of this vital steroid may bridge the gap during the transition from corpus luteum to chorionic hormonal support of the pregnancy. 

It has been argued by some authors that no therapy is indicated in patients who threaten to abort, for in more than one-half of these women threatening symptoms will subside and the pregnancies will culminate successfully. Furthermore, the high incidence of ovular defects decreases tremendously the number of pregnancies that are worth salvaging. However, such an attitude of defeat and resignation does not conform with modern dynamic medicine. If only 5 or 10 per cent of patients in whom the threatened abortion would have become inevitable can be helped to carry their pregnancies by intelligent therapy it is worthwhile.

Sterility, pp. 326-27 (emphasis mine). Dr. Davis continues his enthusiastic endorsement of the "over-abundant" clinical use of synthetic progesterones in “modern dynamic medicine” as follows:

Until the last two years, 100 mg of progesterone in oil was administered intramuscularly to the patient four or five times each week. This was continued until she felt life at about 16 to 18 weeks if on previous occasions she belonged to the group who aborted early in pregnancy. If the pattern for previous abortions indicated that the terminations occurred most often at midpregnancy, however, the medication was continued until the baby reached a safe period of viability, about 6 weeks from term. No other steroids were administered.

The frequency of the intramuscular administration and the occasional discomfort they induced interfered to some extent in the above regimen. Unfortunately, progesterone is metabolized rapidly, for the administration of 50 mg per day to the patient who is not pregnant produces no holdover effects for longer than 48 hours. The introduction of 17a-hydroxyprogesterone caproate (Delalutin) provided a long-acting progestational agent. Although its metabolism differs from crystalline progesterone, its biologic action is similar. The length of its action is dependent on an adequate supply of estrogens. It is possible that additional estrogens may be indicated in some cases. The habitual aborter can now receive 250 mg of 17a-hydroxyprogesterone caproate intramuscularly twice a week, or even 500 mg once a week. There have been no undesirable sequelae following the administration of this new progestational agent. The administration of crystalline progesterone and 17a-hydroxyprogesterone caproate during pregnancy has not resulted in virilism in the newborns in our experience.
[...]
[A]n overabundance of [progesterone] may improve the uterine environment of the conceptus and result in a more adequate circulation, a more substantial implantation, and a quiescent abode for the embryo.

Sterility, pp. 332-333.

It is very important to note that in a subset of infertility patients, the use of corticosteroids such as prednisolone was also advised. These cases included women with adrenogenital syndrome, women with amenorrhea, or infrequent menses, and with no signs of masculinization, patients with fallopian tube obstruction, patients with long- standing infertility, and a group of husbands showing oligospermia. Sterility pp. 381-82. Tyler described the clinical use of prednisolone for fertility as follows:

Patients were given 5 mg four times daily for 2 days, then 5 mg three times daily for 2 days, and then were placed on a maintenance dosage of 5 mg twice daily for 12 weeks, or slightly longer. When therapy was to be discontinued the dosage was tapered off gradually, so that during one week 5 mg was administered daily, and the dose decreased to 5 mg every other day the following 2 weeks, then 5 mg twice a week for 2 weeks, at which time the medication was then stopped.

Sterility, p. 382.

In sum, the literature reflects a once widespread medical practice of prophylactically drugging pregnant women who had suffered more than one previous miscarriage with heavy doses of synthetic hormones, particularly progestins, and to a lesser extent estrogens and corticosteroids, sometimes in combination with each other. This practice was particularly prevalent among somewhat upper income women who could afford the expensive therapies.

I am a perfect example of a child exposed in utero to these synthetic chemicals in the 1960s.  As fate would have it, I was the subject of the study, "Prenatal Exposure to Synthetic Progestins and Estrogens: Effects on Human Development," by Dr. June Reinish.  Thanks to meticulous record-keeping by Dr. Reinisch and the Kinsey Institute, where she had served as director,  I just recently obtained the records of my own exposures.  They were:

Deladroxate (dihydroxyprogesterone acetophenide enanthate, maybe combined with 10-mg estradiol) by injection for 7 weeks, 100 mg once a week (first trimester);

Deluteval (hydroxyprogesterone caproate (also known as Delalutin) plus estradiol valerate) by injection 250 mg every week, for 19 weeks (second and third trimesters); and

Prednisolone, oral, preconception through first trimester, approx. 35 mg for 10 weeks.

A birth control pill has about .2 mg of synthetic hormones. I was exposed to about 6,000 mg [note: at first I thought it was about half that] of these chemicals in utero, most during the first half of pregnancy, the very period during which my eggs developed. As far as I can tell, although millions of us were exposed to these insane and genotoxic anti-miscarriage protocols, I'm the only one who has recovered her prenatal records.

The heavy use of synthetic hormones for anti-miscarriage began to fade in the 1970s, first with the revelations about DES toxicity in 1971, and then with the publication of various studies beginning to question the fetal impacts of these exposures, including, notably, the aforementioned 1977 study of developmental effects by June Reinisch, in which she found distinct personality differences in the exposed children, as compared to their unexposed siblings. The differences can be summed up this way: we were a bit “Aspie,” that is more independent and less groupish, and somewhat gender-bended. Reinisch and others later found prenatal corticosteroid exposure to have teratogenic effects on the fetus, including fetal growth retardation.

OH DEAR, you are thinking, WHY DOES ANY OF THIS MATTER?  I TURNED OUT OKAY, RIGHT?

Yes, I turned out okay, but my children are not.  They are autistic.  Their brains do not work.  They cannot talk.  They cannot learn.  They spend their days engaged in constant stims, like shredding paper or chewing on toys.  They will never have jobs.  They will require tens of millions of dollars in 24/7 support over their lifetimes.  And now, seemingly out of the blue, there are hundreds of thousands of others just like them.

You see, the drugs screwed up my eggs.  The process of fetal germline (egg or sperm) development depends on the appropriate delivery of precise chemical messages, including hormonal molecules. Impostor hormones such as progestins, estrogens or corticosteroids, singularly and in combination, can hijack a fragile and unfathomably complex system that evolved over billions of years, upsetting the normal molecularly-controlled developmental processes necessary for normal sperm and egg development. This process has been demonstrated in a great many studies over the past decade. [FN1]  In addition, as mentioned above, the use of these novel synthetic medications was particularly intense in the first half of pregnancy, which is precisely the timeframe of epigenetic programming of the vulnerable fetal germline.

Did progestins, with or without combined estrogens and corticosteroids scramble the intracellular signals needed for normal epigenetic synthesis, resulting in developmental abnormalities in our egg and sperm, and therefore in our progeny, our children? In light of the vast exposure history, what we know about germline disruption caused by impostor hormones, and the strongly epigenetic nature of neurodevelopment, it is more than plausible, it is indeed highly likely. Already I have found many autism families with prenatal exposure histories just like mine.

It is time for the “hidden history” of mass use of progestins and other endocrine-disrupting synthetic steroid hormone drugs in pregnancy to come out of the closet. Researchers are almost totally ignorant about what occurred in countless doctor's offices over several decades, resulting in one of the greatest toxic events in the history of humanity. No doubt, it will explain a portion of the glut of quasi-genetic disorders in the generation born 1980s to today, a generation rife with autism, ADHD, mental disorders, learning disabilities, and other “idiopathic” public health mysteries of our era. If there is a connection, and of course there is, the implications are vast and of profound importance.


FN1 Endocrine disrupting compounds have repeatedly been shown to induce epimutations and impact gene expression profiles of germ cells, at both low and high doses. See, eg, Manikkam et al, Plastics Derived Endocrine Disruptors (BPA, DEHP and DBP) Induce Epigenetic Transgenerational Inheritance of Obesity, Reproductive Disease and Sperm Epimutations, PLOS One 8(1): e55387. doi:10.1371/journal.pone. 0055387 (2013); Crews, Epigenetic transgenerational inheritance of altered stress responses, PNAS USA. 2012 doi: 10.1073/pnas.1118514109; Susiarjo et al 2013, Bisphenol A Exposure Disrupts Genomic Imprinting in the Mouse, PLoS Genet 9(4): e1003401. doi:10.1371/journal.pgen.1003401; Walker and Gore, Transgenerational neuroendocrine disruption of reproduction, Nature Reviews Endocrinology 7, 197-207 2011. Doyle et al. (2013), Transgenerational Effects of Phthalate on Male Germ Cells, BOR Papers in Press Published on March 27, 2013 as DOI:10.1095/biolreprod.112.106104; Manikkam et al, Dioxin (TCDD) induces epigenetic transgenerational inheritance of adult onset disease and sperm epimutations, PLoS ONE 7(9): e46249. doi:10.1371/journal.pone.0046249 (2012); Del Mazo et al, The effects of different endocrine disruptors defining compound specific alterations of gene expression profiles in the developing testis, Reproductive Toxicology 33:1, 106–115 (2012).