Increased Excretion of Pregnanediol in Pregnancy from Diethylstilbestrol with Special Reference to the Prevention of Late Pregnancy Accidents

Smith, O. Watkins; Smith, George Van S.; Hurwitz, David

doi:10.1016/s0002-9378(16)40020-7

Cited by 134 publications

(15 citation statements)

References 15 publications

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“…Miller has been able to show that a high fetal mortality occurs even though diabetes does not appear in the mother until after the child-bearing period is largely past (Miller, 1945b). Furthermore, there is some evidence that the high fetal and neonatal mortality rates in diabetic pregnancies are related to pathologic alterations in estrogenic and gonadotropic hormones in the mother during pregnancy (White and Hunt, 1943) (Smith, Smith and Hurwitz, 1944) (Smith, et al, 1946) (Rubin, Dorfman and Miller, 1946). It is true that the failure to regulate the diabetes of the mother will lead to a greater fetal mortality rate, witness the higher fetal mortality rates in the days before insulin and in pregnancies complicated by diabetic acidosis (Joslin, 1940).…”

Section: Discussionmentioning

confidence: 99%

The Effect of Pregnancy Complicated by Alloxan Diabetes on the Fetuses of Dogs, Rabbits and Rats

Miller

1947

Endocrinology

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Section: Discussionmentioning

confidence: 99%

The Effect of Pregnancy Complicated by Alloxan Diabetes on the Fetuses of Dogs, Rabbits and Rats

Miller

1947

Endocrinology

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“…Several studies have linked the occurrence of cervical or vaginal CCAC in young women with intrauterine exposure to diethylstilbestrol (DES), a synthetic nonsteroidal estrogenic hormone prescribed to pregnant women in several countries as a preventive therapy against abortion. 2,3 On the other hand, there have also been numerous reports of cervical or vaginal CCAC appearing in young women with no history of intrauterine exposure to DES. 4 As many as 31 cases of CCAC have been reported in Japan, a country where DES has never been prescribed to pregnant women.…”

Section: Introductionmentioning

confidence: 99%

A young woman with clear cell adenocarcinoma of the uterine cervix

Seki

Takada

Sodemoto

et al. 2003

International Journal of Clinical Oncology

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In May 1999, an 18-year-old woman visited a physician because of vaginal bleeding and the excretion of large clots from the vagina. A vaginal tumor was discovered and the patient was referred to our outpatient department. Vaginal examination showed a bleeding, tumor, approximately 6 cm in size, protruding from the cervical os and filling the vagina. The cytological finding of the uterine cervix was class V, and the histological diagnosis by punch biopsy was clear cell adenocarcinoma (CCAC) of the uterine cervix. The patient initially received neoadjuvant chemotherapy (NAC) with intraarterial injections of 8 mg/m(2) of mitomycin, 270 mg/m(2) of etoposide, and 380 mg/m(2) of carboplatin. Although the NAC reduced the size of the tumor, it failed to produce favorable pathological changes and was therefore deemed ineffective. A radical abdominal hysterectomy and pelvic lymphadenectomy were performed on October 12. Macroscopic findings showed a tumor, 6 cm in diameter, growing from the right side of the uterine cervix, with a fragile, necrotic surface. Pathological diagnosis was CCAC of the cervix (pT2a, N0, M0). The patient was discharged from our hospital without any postoperative chemotherapy or radiation therapy. No signs of recurrence have been detected since. We reviewed the literature on CCAC patients in Japan up to the present and compared the data with the data reported in a review of CCAC in the Netherlands. While there were similarities between the patients in the two countries in the patients' pattern of growth and the poor prognosis of the tumors, there was a significant difference between the countries in the patients' history of diethylstilbestrol (DES) exposure. These results suggest that menarche and menopause may play roles in promoting carcinogenesis, or alternatively, that a subpopulation of women are subject to genetic or exogenous risk factors other than DES.

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“…There were studies at that time indicating that compromised pregnancies had a deficient output of the hormone progesterone, and further studies conducted in the late 1940s in Boston using very crude measuring techniques suggested that this deficiency could be corrected by administering DES to the mother, which would then lead to a healthy pregnancy. These studies led to the widespread usage of the drug to prevent pregnancy loss [2][3][4].…”

mentioning

confidence: 99%

Diethylstilbestrol (DES) Pregnancy Treatment: A Promising Widely Used Therapy with Unintended Adverse Consequences

Herbst

Anderson

2015

AMA Journal of Ethics

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Diethylstilbestrol (DES) was first synthesized in 1938 and was the first orally active nonsteroidal estrogen that could be used for human therapy [1]. At that time, endocrinology was in its infancy and this discovery was a unique and great advance. Recurrent pregnancy loss was a serious medical problem then as it is now. It was believed the problems were due to a faulty hormonal environment of the fetal-placental unit, rather than primarily to genetic causes, as we have subsequently learned. There were studies at that time indicating that compromised pregnancies had a deficient output of the hormone progesterone, and further studies conducted in the late 1940s in Boston using very crude measuring techniques suggested that this deficiency could be corrected by administering DES to the mother, which would then lead to a healthy pregnancy. These studies led to the widespread usage of the drug to prevent pregnancy loss [2][3][4].The initial examination of the newborns born to mothers treated with DES during pregnancy showed no abnormalities (C. Smith, personal communication). The treatment, however, was controversial. (A unique double-blind study conducted at the University of Chicago in the early 1950s failed to show any improved pregnancy outcome with DES therapy [5]. This study, while negative, was conducted on a healthy pregnant population, which was different than the Boston Study, which was conducted on a high-risk population with a history of bleeding in pregnancy or multiple pregnancy losses.) An additional problem is that the hormone assays in the Boston Study were later found to be faulty and not to actually measure progesterone (Louis L. Engel, PhD, personal communication). It is believed that DES continued to be heavily used in the 1960s, and it has been estimated that 2 to 4 million women in the United States took DES during pregnancy [6].Then, in the late 1960s, eight extraordinarily rare cases of clear cell adenocarcinoma (CCA) of the vagina were diagnosed and treated in women in their teens and early 20s in the Boston area [7]. No such cluster of cases in young patients had ever been seen previously. CCA of the vagina was known to be a cancer that rarely occurred even in older women. In an effort to understand the cause of this cluster, a case-control study was conducted at the Massachusetts General Hospital in 1971 that linked the appearance of these cancers to the patients' mothers having been treated with DES for pregnancy

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Increased Excretion of Pregnanediol in Pregnancy from Diethylstilbestrol with Special Reference to the Prevention of Late Pregnancy Accidents

Cited by 134 publications

References 15 publications

The Effect of Pregnancy Complicated by Alloxan Diabetes on the Fetuses of Dogs, Rabbits and Rats

The Effect of Pregnancy Complicated by Alloxan Diabetes on the Fetuses of Dogs, Rabbits and Rats

A young woman with clear cell adenocarcinoma of the uterine cervix

Diethylstilbestrol (DES) Pregnancy Treatment: A Promising Widely Used Therapy with Unintended Adverse Consequences

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