DES exposure in utero associated with cryptorchidism, testicular hypoplasia and semen abnormalities

Severe pathological changes found in many DES Sons’ sperm.

Abstract

Association of diethylstilbestrol exposure in utero with cryptorchidism, testicular hypoplasia and semen abnormalities, The Journal of urology, NCBI PubMed PMID: 37351, 1979 Jul.

Epididymal cysts and/or hypoplastic testes have been found in 31.5 per cent of 308 men exposed to diethylstilbestrol in utero, compared to 7.8 per cent of 307 placebo-exposed controls.

Analyses of the spermatozoa have revealed severe pathological changes (Eliasson score greater than 10) in 134 diethylstilbestrol-exposed men (18 per cent) and 87 placebo-exposed men (8 per cent).

Further investigation of the 26 diethylstilbestrol-exposed men with testicular hypoplasia has revealed that 65 per cent had a history of cryptorchidism.

Only 1 of the 6 placebo-exposed controls with testicular hypoplasia had a history of testicular maldescent.

Although none of our Diekmann’s lying-in study group has had carcinoma to date one must keep in mind the reported increased risk of testicular carcinoma in testes that are or were cryptorchid.

A 25-year-old man who was not part of the study group was treated recently by us for a testicular carcinoma ( mixed anaplastic seminoma plus embryonal cell carcinoma) and he had a history of diethylstilbestrol exposure in utero and cryptorchidism.

More DES DiEthylStilbestrol Resources

Impaired reproductive performance in Diethylstilbestrol-exposed women

image of infertility
It is probable that the high rate of infertility and pregnancy wastage in the DES-exposed is related to the uterine structural abnormalities encountered. Image © Infertility. Sticky paralyzing discovery.

Abstract

Impaired reproductive performance in DES-exposed women, Obstetrics and gynecology, NCBI PubMed PMID 7352058, 1980 Jan.
Full text: Obstetrics & Gynecology, January 1980 – Volume 55 – Issue 1, 1980/01000.

The reproductive history of 69 women with demonstrated diethylstilbestrol (DES)-related cervical-vaginal abnormalities is reviewed.

All of the patients were sexually active non-contraceptive users who were studied over an 8-year period.

  • Forty-six patients conceived, for an uncorrected fertility rate of 66.7%. Fourteen patients elected therapeutic abortion.
  • The 32 remaining patients had 62 pregnancies which resulted in 26 living children, for a success rate of 41.9%. However, cervical cerclage was required for continuation of 8 of these successful pregnancies.
  • The 36 pregnancy failures consisted of 19 first- and 11 second-trimester spontaneous abortions, 3 third-trimester losses due to permaturity, and 3 tubal pregnancies.
  • Uterine abnormalities were found in all of the 25 patients who underwent hysterosalpingograms.

Although other reproductive diseases unrelated to DES exposure in utero were also present in this select group of patients, it is probable that the high rate of infertility and pregnancy wastage is related to the uterine structural abnormalities encountered.

Click to download the full study.

More DES DiEthylStilbestrol Resources

Structural and functional abnormalities in the sex organs of male offspring of mothers treated with DES

Severe pathological changes and sperm abnormalities found in many DES Sons. Santalum freycinetianum.

Abstract

Structural and functional abnormalities in the sex organs of male offspring of mothers treated with diethylstilbestrol (DES), The Journal of reproductive medicine, NCBI PubMed PMID: 772199, 1976 Apr.

The in utero effects of DES (Diethylstilbestrol) on the human male genital tract are reported in this follow-up study of male offspring of DES-treated mothers.

Both anatomical and functional abnormalities were significantly greater in the DES-exposed males as compared to control males whose mothers were all participants in a prospective, randomized double blind study of the effects of DES on pregnancy at the Chicago Lying-in Hospital during the early 1950s.

Epididymal cysts, hypotrophic testes and capsular induration of the testes were among the more common genital lesions found in 27 per cent of 134 DES-exposed males as compared to a 7 per cent incidence in 119 control males.

Spermatozoa analyses revealed severely pathologic changes (Eliasson score greater than 10) in 29 per cent of 28 DES-exposed males and 0 per cent of 18 control males (with or without genital i.e., physical abnormalities). Abnormal findings on physical examination combined with sperm abnormalities (Eliasson score greater than or equal to 5) were found in 29 per cent of DES-exposed males versus 0 per cent of 18 control males.

Cytologic examinations did not reveal malignant cells from the following materials: urines before and after prostatic massage or ejaculation, prostatic fluids and aspirates from epididymal cysts.

More DES DiEthylStilbestrol Resources

Fertility and outcome of pregnancy in women exposed in utero to DES

fertility
An increased risk of unfavorable outcome of pregnancy is associated with DES exposure.

Abstract

Fertility and outcome of pregnancy in women exposed in utero to diethylstilbestrol, The New England journal of medicine, NCBI PubMed PMID: 7351908, 1980 Mar 13.

Fertility and outcome of pregnancy were examined in women participating in the National Cooperative Diethylstilbestrol Adenosis (DESAD) Project.

We compared 618 subjects who had prenatal exposure to DES with 618 control subjects. Fertility, measured in terms of pregnancies achieved, did not differ between the women exposed to DES and the controls.

An increased risk of unfavorable outcome of pregnancy was associated with DES exposure (the relative risk of any unfavorable outcome of pregnancy was 1.69; P less than 0.001). Speculation on biologic mechanisms that might produce this difference is premature, since additional data about these subjects must be collected.

Among DES-exposed women who became pregnant, 81 per cent had at least one full-term live birth.

More DES DiEthylStilbestrol Resources

Abnormal semen analyses in the DES-exposed males

oligospermia
Oligozoospermia, refers to semen with a low concentration of sperm and is a common finding in male infertility.

Abstract

DES Effect on Males, Pediatrics, January 1978, VOLUME 61 / ISSUE 1 61/1/154.3.

We have found defects in the urogenital tract of males exposed to diethylstilbestrol (DES) in utero, but the anomalies are different than those expected from the data of Henderson and co-workers. They reported an increased incidence of suspected urethral stenosis in boys exposed to DES. Their conclusion was drawn from the response of 225 DES-exposed males to a questionnaire.

We have thoroughly examined 163 DES-exposed males and found a significantly increased incidence of

  • oligospermia,
  • hypotrophic testes,
  • low ejaculate volumes,
  • epididymal cysts,
  • and microphallus.
More DES DiEthylStilbestrol Resources

Spermatozoal analysis in the DES-exposed males

Abstract

Pathological semen and anatomical abnormalities of the genital tract in human male subjects exposed to diethylstilbestrol in utero, The Journal of urology, NCBI PubMed PMID: 850321, 1977 Apr.

The in utero effects of diethylstilbestrol on the human male genital tract are reported in our followup study of male offspring of mothers treated with diethylstilbestrol.

Anatomical and functional abnormalities were significantly greater in male patients exposed to diethylstilbestrol compared to male controls whose mothers were all participants in a prospective, randomized double-blind study on the effects of diethylstilbestrol on pregnancy at our hospital during the early 1950s.

Epididymal cysts, hypotrophic testes and capsular induration of the testes were among the more common genital lesions found in more than 25 per cent of 159 male patients exposed to diethylstilbestrol compared to a 6.8 per cent incidence in 161 male controls.

Spermatozoal analysis revealed severe pathological changes (Eliasson score more than 10) in 32 per cent of 31 patients exposed to diethylstilbestrol and 0 per cent of 20 male controls. Abnormal findings on physical examination combined with severe sperm abnormalities (Eliasson score more than 10) were found in 23 per cent of the male patients exposed to diethylstilbestrol versus none of the male controls.

Cytologic examinations revealed no malignant cells from urine samples before and after prostatic massage or ejaculation, prostatic fluids and aspirates from epididymal cysts.

More DES DiEthylStilbestrol Resources

Reproductive outcomes in men with prenatal exposure to diethylstilbestrol

This 2005 study suggested that DES-exposed men are more likely than the unexposed to have an experience with infertility ; the effect/risk increasing iwith advancing age.

Abstract

Reproductive outcomes in men with prenatal exposure to diethylstilbestrol, Fertility and sterility, NCBI PubMed PMID: 16359959, 2005 Dec.
Full study: Fertility and sterility, December 2005 Volume 84, Issue 6, Pages 1649–1656, S0015-0282(05)02956-0, 2005 Dec.

OBJECTIVE
To examine prenatal diethylstilbestrol (DES) exposure in relation to male reproductive outcomes.

DESIGN
Prospective observational study.

SETTING
Participants were identified through record review, clinical trial participation, or an obstetrics clinic.

PATIENT(S)
A total of 1,085 DES-exposed and 1,047 unexposed men.

INTERVENTION(S)
Participants were exposed prenatally to DES through the mother’s obstetrics care or clinical trial participation.

MAIN OUTCOME MEASURE(S)
Infertility; never fathering a pregnancy or live birth; number of pregnancies or live births fathered.

RESULT(S)
We found little evidence that prenatal DES exposure affects the likelihood of never fathering a pregnancy or live birth, or influences the mean number of fathered pregnancies or live births.

  • Our data suggest that DES-exposed men are slightly more likely to experience infertility (relative risk [RR] = 1.3, 95% confidence interval [CI] = 1.0-1.6).
  • The DES dose and gestational timing did not influence infertility or the number of pregnancies or live births fathered, but results were inconsistent for dose effects on the likelihood of never fathering a pregnancy or a live birth.

CONCLUSION(S)
Prenatal DES exposure may be associated with a slightly increased risk of having an infertility experience, but does not increase the likelihood of never fathering a pregnancy or a live birth, or the number of pregnancies or live births fathered.

Although speculative, this data may reflect an increased effect of DES on infertility with advancing age.

Click to download the full study.

More DES DiEthylStilbestrol Resources

Infertility among women exposed prenatally to diethylstilbestrol

This 2001 study, which is larger and includes a considerably longer follow-up period than any previous study, indicates that women exposed to diethylstilbestrol in utero have an increased risk of infertility, both primary and secondary, and that the increase is primarily due to tubal and uterine factors. I is for Infertility.

Abstract

Infertility among women exposed prenatally to diethylstilbestrol, American journal of epidemiology, NCBI PubMed PMID: 11495854, 2001 Aug.
Full study: Am. J. Epidemiol, doi: 10.1093/aje/154.4.316, January 17, 2001.

Although it is well established that women exposed to diethylstilbestrol in utero have an increased risk of spontaneous abortion, ectopic pregnancy, and preterm delivery, it is not known whether they also have an increased risk of infertility. The authors assessed this question in data from a collaborative follow-up study of the offspring of women who took diethylstilbestrol during pregnancy.

In 1994, 1,753 diethylstilbestrol-exposed and 1,050 unexposed women from an ongoing cohort study (National Cooperative Diethylstilbestrol Adenosis Study and Dieckmann cohorts) provided data on difficulties in conceiving and reasons for the difficulty. Age-adjusted relative risks were computed for the association of diethylstilbestrol exposure with specific types of infertility.

  • A greater proportion of exposed than unexposed women were nulligravid (relative risk (RR) = 1.3, 95% confidence interval (CI): 1.1, 1.5),
  • and a greater proportion had tried to become pregnant for at least 12 months without success (RR = 1.8, 95% CI: 1.6, 2.1).
  • Diethylstilbestrol exposure was significantly associated with infertility due to uterine and tubal problems, with relative risks of 7.7 (95% CI: 2.3, 25) and 2.4 (95% CI: 1.2, 4.6), respectively.

The present findings indicate that diethylstilbestrol-exposed women have a higher risk of infertility than do unexposed women and that the increased risk of infertility is primarily due to uterine or tubal problems.

Click to download the full study.

More DES DiEthylStilbestrol Resources

Female fertility prognosis and diethylstilbestrol. Personal data and review of the literature

In spite of their difficult past reproductive history 4 young DES-women conceived successfully with adapted psychological and medical care in 1998 in France. Las manos del destino.

Abstract

Female fertility prognosis and diethylstilbestrol, Journal de gynécologie, obstétrique et biologie de la reproduction, NCBI PubMed PMID: 9648005, 1998 Apr.
Full study: em-consulte, Doi : JG-05-1998-27-3-0368-2315-101019-ART95, 1998.

Diethylstilbestrol (DES) exposure in utero in females is a cause of clear-cell adenocarcinoma of the cervix and of several anatomical and functional disorders of the genital tract. DES exposure must be evoked whenever counselling women for reproductive disorders.

In France around 80,000 women have had in utero DES exposure. The cases of four young women who consulted our Reproduction Center for reproductive disorders illustrate the usual difficulties faced by these patients.

In spite of their difficult past reproductive history (uterine malformations, repeated miscarriages, ectopic pregnancies) and low fertility rate, all four women conceived successfully, either after spontaneous or induced ovulation. We stress the need for adapted psychological and medical care which can lead to successful childbearing in the vast majority of these high-risk patients.

Click to download the full study.

More DES DiEthylStilbestrol Resources

Fertility in men exposed prenatally to diethylstilbestrol

In this 1995 survey of nearly 500 exposed and unexposed men, researchers say they found no evidence that diethylstilbestrol impairs male fertility.

Abstract

Fertility in men exposed prenatally to diethylstilbestrol, The New England journal of medicine, NCBI PubMed PMID: 7723797, 1995 May 25.
Full study: The NEJM, DOI: 10.1056/NEJM199505253322104, 1995 May 25.

BACKGROUND
Prenatal exposure to diethylstilbestrol causes infertility in male mice and has been associated with malformations of the genital tract in men. However, little is known about the fertility of men who have been exposed prenatally to diethylstilbestrol.

METHODS
In 1950 through 1952, 1646 pregnant women were enrolled in a randomized, placebo-controlled clinical trial of diethylstilbestrol at Chicago Lying-in Hospital. We interviewed men who were born to the women during that study about their fertility.

RESULTS
Four decades after their birth, we were able to trace 548 of the surviving sons (68 percent). Ninety percent consented to be interviewed (253 who had been exposed to diethylstilbestrol in utero and 241 who had not been exposed).

  • Congenital malformations of the genitalia were reported three times as often by the diethylstilbestrol-exposed men as by the sons of the women in the placebo group.
  • Within the exposed group, malformations were reported twice as often among those exposed to diethylstilbestrol before the 11th week of gestation as among those exposed later (P = 0.05).
  • Men with genital malformations were nonetheless as fertile as other men.
  • The diethylstilbestrol-exposed men (with or without genital malformations) had no impairment of fertility by any measure, including whether they had ever impregnated a women, age at the birth of their first child, average number of children, medical diagnosis of a fertility problem, or length of time to conception in the most recent pregnancy of the female partner.
  • Finally, diethylstilbestrol-exposed men had no impairment of sexual function, as indicated, for example, by the frequency of intercourse or reported episodes of decreased libido.

CONCLUSIONS
High doses of diethylstilbestrol did not lead to impairment of fertility or sexual function in adult men who had been exposed to the drug in utero.

NB: this data focused exclusively on fertility outcomes, it does not address any of DES side-effects and/or health effects of diethylstilbestrol that might emerge at older ages.

Click to download the full study.

More DES DiEthylStilbestrol Resources