Search PubMed⌕ Search

Biomedical subjects

A L Herbst

Publications and source records attributed to A L Herbst.

At least 19 recordsLinked to original sources
PubMed2001

Infertility among women exposed prenatally to diethylstilbestrol.

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.

Adult↗
PubMed2001

Cancer risk in men exposed in utero to diethylstilbestrol.

BACKGROUND: An association between prenatal diethylstilbestrol (DES) exposure and cancer in men, especially testicular cancer, has been suspected, but findings from case-control studies have been inconsistent. This study was conducted to investigate the association between prenatal DES exposure and cancer risk in men via prospective follow-up. METHODS: A total of 3613 men whose prenatal DES exposure status was known were followed from 1978 through 1994. The overall and site-specific cancer incidence rates among the DES-exposed men were compared with those of the unexposed men in the study and with population-based rates. The relative rate (RR) was used to assess the strength of the association between prenatal DES exposure and cancer development. All statistical tests were two-sided. RESULTS: Overall cancer rates among DES-exposed men were similar to those among unexposed men (RR = 1.07; 95% confidence interval [CI] = 0.58 to 1.96) and to national rates (RR = 0.99; 95% CI = 0.65 to 1.44). Testicular cancer may be elevated among DES-exposed men, since the RRs for testicular cancer were 3.05 (95% CI = 0.65 to 22.0) times those of unexposed men in the study and 2.04 (95% CI = 0.82 to 4.20) times those of males in the population-based rates. The higher rate of testicular cancer in the DES-exposed men is, however, also compatible with a chance observation. CONCLUSIONS: To date, men exposed to DES in utero do not appear to have an increased risk of most cancers. It remains uncertain, however, whether prenatal DES exposure is associated with testicular cancer.

Carcinogens↗
PubMed2001

Long-term cancer risk in women given diethylstilbestrol (DES) during pregnancy.

From 1940 through the 1960s, diethylstilbestrol (DES), a synthetic oestrogen, was given to pregnant women to prevent pregnancy complications and losses. Subsequent studies showed increased risks of reproductive tract abnormalities, particularly vaginal adenocarcinoma, in exposed daughters. An increased risk of breast cancer in the DES-exposed mothers was also found in some studies. In this report, we present further follow-up and a combined analysis of two cohorts of women who were exposed to DES during pregnancy. The purpose of our study was to evaluate maternal DES exposure in relation to risk of cancer, particularly tumours with a hormonal aetiology. DES exposure status was determined by a review of medical records of the Mothers Study cohort or clinical trial records of the Dieckmann Study. Poisson regression analyses were used to estimate relative risks (RR) and 95% confidence intervals (CI) for the relationship between DES and cancer occurrence. The study results demonstrated a modest association between DES exposure and breast cancer risk, RR = 1.27 (95% CI = 1.07-1.52). The increased risk was not exacerbated by a family history of breast cancer, or by use of oral contraceptives or hormone replacement therapy. We found no evidence that DES was associated with risk of ovarian, endometrial or other cancer.

Breast Neoplasms↗
PubMed2001

The management of ASCUS cervical cytologic abnormalities and HPV testing: a cautionary note.

A recently published study of the management of low-grade cytologic smears compared immediate colposcopy to human papillomavirus (HPV) triage and entry cytology smears (conservative management) as three triage techniques for managing atypical squamous cells of undetermined significance (ASCUS) smears (Atypical Squamous Cells of Undetermined Significance/Low-grade Squamous Intraepithelial Lesion Triage Study [ALTS]). The study reported a high sensitivity (96.3%) for HPV testing using hybrid capture 2 to detect cervical intraepithelial neoplasia (CIN) III. The authors concluded that HPV testing is a viable option for managing ASCUS smears. We have reviewed the published data from the ALTS trial and have found a large excess of colposcopies and biopsies in the HPV arm in comparison with the conservative management (cytology) arm. In addition, the ALTS trial quality control and pathology review results raise doubts about the diagnostic validity of the study to establish standards of clinical practice. Furthermore, until the 2-year follow-up analysis of the conservative management arm is completed to detect CIN III, a valid comparison between HPV triage and conservative management is not possible. We conclude that, based on published data, HPV testing for routine clinical management of low-grade cytologic abnormalities (ASCUS smears) is not warranted, and that HPV testing is currently an investigational tool.

Colposcopy↗
PubMed2001

Incidence of squamous neoplasia of the cervix and vagina in women exposed prenatally to diethylstilbestrol (United States).

OBJECTIVES: Women exposed prenatally to diethylstibestrol (DES) have an excess risk of clear-cell adenocarcinoma of the vagina and cervix, but the effect on the incidence of squamous neoplasia is uncertain. The purpose of the current study was to evaluate the long-term risk of developing high-grade squamous neoplasia of the genital tract among women exposed prenatally to DES. METHODS: A cohort comprising 3,899 DES-exposed and 1,374 unexposed daughters was followed for 13 years (1982 1995) for pathology-confirmed diagnoses of high-grade squamous intraepithelial neoplasia (HSIL) of the genital tract. Poisson regression analysis was used to compute relative risks (RR) and 95% confidence intervals (95% CI), adjusting for age, calendar year, and other covariates. RESULTS: The RR (95% CI) among DES-exposed versus unexposed, based on 111 cases of high-grade disease, was 2.1 (1.2-3.8). Adjustment for screening history estimated by the number of years since the last Pap smear had little effect. Risk estimates were higher with earlier intrauterine exposure; the RR (95% CI) for exposure within 7 weeks of the last menstrual period was 2.8 (1.4-5.5). Only two cases of invasive squamous cervical cancer occurred in total, precluding separate analysis. CONCLUSIONS: The findings support an association between in-utero DES exposure and high-grade squamous neoplasia, although a role for more intensive screening among DES-exposed women in the production of this excess could not be completely ruled out.

Carcinoma, Squamous Cell↗
PubMed2000

Continued follow-up of pregnancy outcomes in diethylstilbestrol-exposed offspring.

OBJECTIVE: To evaluate long-term pregnancy experiences of women exposed to diethylstilbestrol (DES) in utero compared with unexposed women. METHODS: This study was based on diethylstilbestrol-exposed daughters, the National Collaborative Diethylstylbistrol Adenosis cohort and the Chicago cohort, and their respective nonexposed comparison groups. Subjects who could be traced were sent a detailed questionnaire in 1994 that contained questions on health history, including information on pregnancies and their outcomes. We reviewed 3373 questionnaires from exposed daughters and 1036 questionnaires from unexposed women. RESULTS: The response rate was 88% among exposed and unexposed women. Diethylstilbestrol-exposed women were less likely than unexposed women to have had full-term live births and more likely to have had premature births, spontaneous pregnancy losses, or ectopic pregnancies. Full-term infants were delivered in the first pregnancies of 84.5% of unexposed women compared with 64. 1% of exposed women identified by record review (relative risk [RR] 0.76, confidence interval [CI] 0.72, 0.80). Preterm delivery of first births occurred in 4.1% of unexposed compared with 11.5% of exposed women, and ectopic pregnancies in 0.77% of unexposed compared with 4.2% of exposed women. Spontaneous abortion was reported in 19.2% of DES-exposed women compared with 10.3% in control women (RR 2.00, CI 1.54, 2.60). According to complete pregnancy histories (many women had more than one pregnancy), preterm births were more common in DES-exposed women (19.4% exposed versus 7.5% unexposed (RR 2.93 CI 2.23, 3.86). Second-trimester spontaneous pregnancy losses were more common in DES-exposed women (6.3% versus 1.6%; RR 4.25, CI 2.36, 7.66). More first-trimester spontaneous abortions occurred in DES-exposed women than in controls (RR 1.31, CI 1.13, 1.53), and DES-exposed women had at least one ectopic pregnancy more often than unexposed women (RR 3.84, CI 2.26, 6.54). CONCLUSION: Pregnancy outcomes in DES-exposed women were worse than those in unexposed women.

Abortion, Spontaneous↗
PubMed2000

Risk factors for diethylstilbestrol-associated clear cell adenocarcinoma.

OBJECTIVE: To assess the influence of postnatal factors on the development of clear cell adenocarcinoma in women exposed to diethylstilbesterol (DES), particularly factors related to exogenous or endogenous hormone exposures, and to reassess the relation of season of birth. METHODS: For the analysis of postnatal factors, 244 cases were compared with 244 age-matched DES-exposed women. Information was obtained from telephone interviews, with questions asked in reference to an index age, the age at which clear cell adenocarcinoma was diagnosed. For the analysis of season of birth, 604 cases, living or deceased, were compared with 1749 DES-exposed women. RESULTS: Neither oral contraceptive (OC) use nor pregnancy was associated with risk of clear cell adenocarcinoma: the odds ratios (OR) were 1.1 (95% confidence interval [CI] 0.7, 1.8) for OC use and 1.3 (95% CI 0.7, 2.3) for pregnancy. The OR for fall season of birth relative to all other seasons was 1.2 (95% CI 0.9, 1.4). CONCLUSION: Pregnancy and OCs do not increase risk of DES-associated clear cell adenocarcinoma. In addition, season of birth does not appear to be a material factor; the previous finding of an increased risk for fall season of birth is most likely not valid and probably a chance finding due to small sample size.

Adenocarcinoma, Clear Cell↗
PubMed1996

Self-reported allergy, infection, and autoimmune diseases among men and women exposed in utero to diethylstilbestrol.

Immunotoxicology studies of prenatal or neonatal exposure to diethylstilbestrol (DES) show effects on immune function of the adult animal. Prenatally exposed humans are known to be at increased risk of vaginal adenocarcinoma, but little research has been done to assess immunologic function. A placebo-controlled clinical trial of DES was conducted in the early 1950s. The sons and daughters born to participants of this clinical trial were traced and interviewed about immune-related health problems. Symptom and disease rates for the DES exposed (253 sons and 296 daughters) were compared with rates for the unexposed (241 men and 246 women). DES-exposed men and women reported rates of allergy, infection, and autoimmune disease similar to the unexposed. However, because autoimmune diseases are rare, a larger sample is needed to evaluate further DES-associated risk of autoimmunity.

Adult↗
PubMed1995

Fertility in men exposed prenatally to diethylstilbestrol.

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.

Abnormalities, Drug-Induced↗
PubMed1995

Onset of menopause in women exposed to diethylstilbestrol in utero.

OBJECTIVES: As part of a larger health survey, we sought to determine whether prenatal exposure to diethylstilbestrol is associated with onset of early menopause or menopausal symptoms. STUDY DESIGN: Diagnosis of premature ovarian failure and symptoms of menopause were determined in a telephone interview with 542 women whose mothers participated in a randomized clinical trial of the use of diethylstilbestrol in pregnancy in the early 1950s. These women were aged 37 to 39 at the time of the interview. Medical records were obtained to confirm diagnosis of premature ovarian failure. RESULTS: The prevalence of menopausal symptoms (specifically hot flashes and night sweats) did not differ for exposed and unexposed women. One exposed woman and no unexposed women had a medically confirmed diagnosis of premature ovarian failure. CONCLUSIONS: Prenatal diethylstilbestrol exposure was not related to diagnosis or symptoms of menopause in this study. Further follow-up will be necessary to determine if a difference in age at menopause emerges as these women become older.

Adult↗
PubMed1995

Age at menarche among diethylstilbestrol granddaughters.

We interviewed 542 women whose mothers were in a randomized trial of diethylstilbestrol. Effects of diethylstilbestrol on the third generation were explored by ascertaining age at menarche for the women's daughters. A total of 123 daughters were > or = 10 years old (52 exposed and 71 unexposed). Age at menarche was unaffected by mother's prenatal diethylstilbestrol exposure.

Adolescent↗
PubMed1994

Influence of in utero diethylstilbestrol exposure on the prognosis and biologic behavior of vaginal clear-cell adenocarcinoma.

Most young women with clear-cell adenocarcinoma (CCA) of the vagina have a history of prenatal exposure to diethylstilbestrol (DES). Some, however, develop vaginal CCA without a prior history of DES exposure. We hypothesized that the natural history of DES-exposed vaginal CCA and DES-unexposed vaginal CCA may differ. Cases were identified from the Registry for Research on Hormonal Transplacental Carcinogenesis which maintains information on cases of CCA of the lower genital tract occurring in women born after 1940. Four hundred and thirty-one cases satisfied FIGO criteria for primary vaginal carcinoma of which 318 had prenatal, hospital, obstetrician, or pharmacy records available for review. Of these, 80% (255/318) had written documentation of prenatal exposure to DES (DES+) and 20% (63/318) had no evidence of DES exposure (DES-) in their medical records. DES exposure was undetermined in 113 cases due to lack of appropriate medical records. Among cases with documentation, DES exposure was not associated with mean age at diagnosis, (DES+, 20.3 years, DES-, 21.1 years), stage (stage I: DES+, 59%, DES-, 54%; stage II: DES+, 32%, DES-, 33%; stage III: DES+, 7%, DES-, 11%; stage IV: DES+, 2%, DES-, 2%, mean tumor diameter or surface area, grade, histology, cell type, or initial therapy. Among cases which underwent pelvic and paraaortic lymph node sampling (DES+, 63%; DES-, 56%; P = NS) the prevalence of pelvic node involvement was similar (DES+, 18.6%; DES-, 17.1%). However, only 1.2% (2/161) of DES+ cases had positive paraaortic lymph nodes compared to 8.6% (3/35) of DES- cases (P = 0.041). Survival differed significantly between the two groups. Probability of survival at 5 and 10 years for DES+ cases was 84 and 78%, respectively, compared to 69 and 60%, respectively, for DES- cases (5 years, P = 0.007, and 10 years, P = 0.008). Presently, 21% (53/255) of DES+ cases are known to have died, compared to 37% (23/63) of DES- cases (P = 0.008). Sites of disease recurrence also differed. DES- cases were more likely than DES+ cases to present with or to later develop distant tumor to the lungs (24% vs 9%; P = 0.002) or metastases to supraclavicular lymph nodes (8% vs 1.6%; P = 0.017). Among the 113 cases with an uncertain history of DES exposure, survival was intermediate between the well-documented cases (79% at 5 years and 65% at 10 years with 35/113 or 31% known dead), as was frequency of metastases to the lungs (13%) or supraclavicular lymph nodes (5.3%).(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma, Clear Cell↗