Fertility in Men exposed prenatally to DiEthylStilbestrol

DiEthylStilbestrol usage review buttress the need for adequate and rigorous research into the use of drugs in pregnancy and ensure that they do more good than harm before being introduced

Abstract

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In that 1995 study, DES sons with genital malformations were nonetheless as fertile as other men.

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.

Sources

  • Fertility in men exposed prenatally to diethylstilbestrol, NCBI, PMID: 7723797, ;332(21):1411-6, 1995 May 25.
  • Full text – New England Journal of Medicine 1995; 332:1411-1416, DOI: 10.1056/NEJM199505253322104, May 25, 1995.
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Effects on the Menstrual Cycle of in Utero Exposure to DiEthylStilbestrol

DiEthylStilbestrol usage review buttress the need for adequate and rigorous research into the use of drugs in pregnancy and ensure that they do more good than harm before being introduced

Abstract

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DiEthylStilbestrol usage review buttress the need for adequate and rigorous research into the use of drugs in pregnancy and ensure that they do more good than harm before being introduced for consumption.

OBJECTIVES:
The purpose of this study was to determine the effects of in utero exposure to diethylstilboestrol on the menstrual cycle.

STUDY DESIGN:
This was a prospective cohort study of 198 diethylstilbestrol-exposed women and 162 unexposed controls, recruited from women whose mothers participated in a randomized trial of diethylstilbestrol in pregnancy at the Chicago Lying-In Hospital from 1950 to 1952. Women with severe menstrual abnormality were excluded from the study.

RESULTS:
Diethylstilbestrol exposure was associated with a statistically significantly decreased duration of menstrual bleeding of approximately one half day and a lower average daily bleeding score (self-reported). We found no evidence for effects of diethylstilbestrol exposure on cycle length or variability of cycle length. Exposure was not related to symptoms of dysmenorrhea.

CONCLUSIONS:
The decreased duration and amount of menstrual bleeding among diethylstilbestrol-exposed women could be due to direct effects on the uterus. The lack of an effect on cycle length and variability appears to indicate that endocrine function is not grossly disturbed in those women studied.

Sources:
  • Effects on the menstrual cycle of in utero exposure to diethylstilbestrolNCBI, PMID: 8141188,
    Am J Obstet Gynecol. 1994 Mar;170(3):709-15.
  • Full text: American Journal of Obstetrics and Gynecology, S0002937894702683, DOI: 10.1016/S0002-9378(94)70268-3.
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A Twenty-Five-Year Follow-Up Study of Women exposed to DiEthylStilbestrol during Pregnancy

DES usage review buttress the need for adequate and rigorous research into the use of drugs in pregnancy and ensure that they do more good than harm before being introduced

Abstract

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DiEthylStilbestrol usage review buttress the need for adequate and rigorous research into the use of drugs in pregnancy and ensure that they do more good than harm before being introduced for consumption.

To assess the long-term effects of diethylstilboestrol (DES) we conducted a health survey among 693 mothers who had taken the drug during pregnancy and a comparable group of 668 who had not. These women had participated in a study during 1951-52 to evaluate the drug. There were 32 (4.6 per cent) breast cancers among the 693 exposed and 21 (3.1 per cent) among the 668 unexposed, but the difference was not statistically significant (P = 0.16). No statistically significant differences occurred between the groups in any of the other categories of disease. The occurrence of breast cancer in both groups was compared to the Connecticut State Tumor Registry for 1963-65. Compared to the registry data, a significantly (P less than 0.01) higher incidence of breast cancer occurred in both the exposed and unexposed groups at ages over 50. The reason for this increase is not known, but effects linked to the selection of mothers participating in the original clinical study cannot be excluded.

Sources:
  • A twenty-five-year follow-up study of women exposed to diethylstilbestrol during pregnancy,
    NCBI, PMID: 628409, N Engl J Med. 1978 Apr 6;298(14):763-7.
  • Full text: NEJM, 197804062981403,
    N Engl J Med 1978; 298:763-767April 6, 1978DOI: 10.1056/NEJM197804062981403
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DiEthylStilbestrol Resources: Fertility and Pregnancy

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DES and Fertility

DES and Pregnancy

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DiEthylStilbestrol Resources: Gestational DES-Exposure and Side-Effects

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In-Utero Exposure to DES

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NCBI PubMed DiEthylStilbestrol Resources: Fetal DES-Exposure and Side-Effects.

DES Side Effects

– Bones

– Endometriosis

– Menarche

– Menopause

– Obesity

– Various Studies

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DiEthylStilbestrol Resources: Cancer, Breast Cancer, CCAC, Vaginal Cancer, Screening

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Cancer

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NCBI PubMed DiEthylStilbestrol Resources: Cancer, Breast Cancer, CCAC, Vaginal Cancer, Screening.

– Breast Cancer

– Clear Cell AdenoCarcinoma and Vaginal Cancer

– Screening

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Cervical Screening and general Physical Examination Behaviors of Women exposed to DES

One third of DES-exposed women are not receiving annual Pap smear examinations

DES Follow-up Study Summary

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One third of DES-exposed women are not receiving annual Pap smear examinations.

In this study we evaluated whether women who were exposed in utero to Diethylstilbestrol (DES) follow the recommendations for cervical screening and general physical examinations.

DES-exposed (3140) and unexposed women (826) from the Houston, Boston, Rochester and Los Angeles sites reported on the 1994 questionnaire how frequently over the preceding five years (1990-1994) they had Papanicolau (Pap) smears and general physical examinations.

The study found that DES-exposed women exceeded the recommended frequency of Pap smear screenings compared to unexposed women. The DES exposed women also exceeded the annual recommendations for physical examinations among women without a history of chronic disease when compared to unexposed women. Whereas most DES-exposed women are receiving cervical cancer screening at recommended intervals, a third are not having these annual Pap smear examinations.

2008 Study Abstract

Objective:
To estimate whether women exposed in utero to diethylstilbestrol (DES) report receiving more cervical and general physical examinations compared to unexposed women.

Materials and Methods:
1994 Diethylstilbestrol Adenosis cohort data are used to assess the degree of recommended compliance of cervical screenings found in 3,140 DES-exposed and 826 unexposed women. Participants were enrolled at 4 sites: Houston, Boston, Rochester, and Los Angeles. Logistic regression modeling was used to analyze mailed questionnaire data, which included reported frequency over the preceding 5 years (1990-1994) of Papanicolaou smears and general physical examinations.

Results:
Diethylstilbestrol-exposed women exceeded the recommended frequency of Papanicolaou smear screenings [adjusted odds ratio (aOR) = 2.15, 95% CI (confidence interval) = 1.60-2.88] compared to the unexposed. This association held among those without a history of cervical intraepithelial neoplasia (aOR = 1.88, 95% CI = 1.35-2.62). Diethylstilbestrol-exposed women exceeded annual recommendations for physical examinations (aOR = 2.27, 95% CI = 1.16-4.43) among women without a history of chronic disease when compared to unexposed women.

Conclusions:
Most DES-exposed women are receiving cervical cancer screening at least at recommended intervals, but one third of the women are not receiving annual Papanicolaou smear examinations.

Sources

  • Cervical screening and general physical examination behaviors of women exposed in utero to diethylstilbestrolNCBI, PMID: 18369304, 2008 Apr;12(2):111-7. doi: 10.1097/LGT.0b013e31815ae980.
  • NCI, DES Follow-up Study Published Papers.
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Vaginal Adenosis, Detection and Value of Screening Procedures

In utero DES-exposure associated with vaginal adenosis in DES Daughters

Value of screening procedures for the detection of vaginal adenosis
In utero exposure to Stilbestrol associated with vaginal adenosis in DES Daughters

Description:
Vaginal Adenosis (submucosal glands lined by mullerian-type epithelium) was rarely described in the past. It has been seen frequently in young women whose mothers took diethylstilbestrol and similar compounds during pregnancy. The adenosis can appear as a red granular lesion. Biopsy of these red areas as well as those that initially appear normal but fail to stain with Schiller’s iodine can usually be accomplished in the office. Although these glands appear to be benign, they
have been observed in close proximity to clear cell adenocarcinomas that have also occurred in young females whose mothers took stilbestrol during pregnancy. Present estimates suggest that the carcinomas are rare among the exposed population while adenosis occurs frequently. Although adenosis has been treated by surgical excision and local destruction (cauterization), the natural history of stilbestrol-associated adenosis is unknown. Close follow-up of patients with vaginal adenosis is certainly indicated and in many instances might prove to be the most prudent approach.

Study:
This study describes the use of routine vaginal iodine staining and other screening procedures for the detection of vaginal adenosis in 3871 postpubertal female patients. Iodine staining identified 65 patients with nonstaining areas in the vagina. Colposcopy verified the presence of vaginal adenosis in 11 of the 65 patients. Directed biopsies confirmed the diagnosis in 10 patients. The iodine staining procedure detected vaginal adenosis in only 1 patient who did not have a positive history of DES exposure or coexisting physical findings. Iodine staining of the vagina has little value as a screening procedure for the detection of vaginal adenosis. Based on these findings, a careful medical history and vaginal examination are recommended as the most productive routine screening procedures for vaginal adenosis. Evaluation and followup of those patients with a history of DES exposure in utero or physical findings suggestive of vaginal adenosis should include vaginal Papanicolaou smears supplemented by colposcopy at 6-month to 1-year intervals. Colposcopically directed biopsies of all abnormal areas should be obtained.

Sources: Value of screening procedures for the detection of vaginal adenosisNCBI, Dr Herbst A, Mar 1976

Screening for DES Daughters

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Vaginal and Cervical Abnormalities, including CCA, related to PreNatal Exposure to Stilbestrol

In utero DES exposure associated with severe clear-cell adenocarcinoma in DES Daughters

Vaginal and cervical abnormalities, including clear-cell adenocarcinoma, related to prenatal exposure to stilbestrol
In utero exposure to Stilbestrol associated with severe clear-cell adenocarcinoma in DES Daughters

A variety of vaginal and cervical abnormalities have been encountered in the offspring of women who have taken stilbestrol or chemically related nonsteroidal estrogens during pregnancy.

Cervical erosion has been noted most often, but vaginal adenosis has been proven by biopsy in over 30 percent, and transverse vaginal and cervical ridges have been seen in approximately 10 percent of the exposed population. Although the use of these drugs had been widespread during the last two decades, the Registry of Clear-Cell Adenocarcinoma of the Genital Tract in Young Females has been able to collect only 170 cases of vaginal and cervical cancers of this type from all over the world.

It is important that cytologists and pathologists become familiar with the various non-enoplastic and neoplastic disorders related to these hormones in order that additional epidemiologic, clinical and pathological information be acquired without delay.

Sources: Vaginal and cervical abnormalities, including clear-cell adenocarcinoma, related to prenatal exposure to stilbestrolNCBI, Dr Herbst A, Jul 1974.

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DiEthylStilbestrol and other Sex Hormones during Pregnancy

DES has terrible side-effects in DES Daughters, DES Sons, DES Grand-Children…

Diethylstilbestrol and other sex hormones during pregnancy
In utero exposure to Diethylstilbestrol is associated with terrible side-effects in DES Daughters, DES Sons, DES Grand-Children

Intrauterine exposure to diethylstilbestrol (DES) has been associated with this subsequent rare development of clear cell adenocarcinoma of the vagina and cervix in exposed female progeny. These tumors have been seen thus far in patients between the ages of 7 and 29 years. In addition, nonmalignant epithelial and structural genital alterations have been frequently observed. The epithelial changes of adenosis, ectropion, metaplasia, and potential neoplasia are considered. Thus far, no increased risk of squamous cell neoplasia has been demonstrated in DES-exposed subjects. However, increased pregnancy wastage, including premature birth, does appear to be more common among DES-exposed women; this increase may be related to the structural uterine and cervical changes that have occurred. DES-exposed men have been demonstrated to have anatomic genital changes, but the effects of these changes, if any, on male infertility are not known. Masculinization of the female external genitalia, including phallic enlargement and labioscrotal fusion, has been reported following intrauterine exposure to certain progestational agents and androgens.

Sources: Diethylstilbestrol and other sex hormones during pregnancyNCBI, Dr Herbst A, Nov 1981.

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