RESUMEN

PIP: It is estimated that 2 million US women used diethylstilbestrol (DES), a nonsteroidal estrogen, to reduce the risk of fetal loss from the late 1940s through the early 1960s. The results of clinical trials of the effectiveness of DES in the early 1950s precipitated the eventual decline of DES prescription by the 1960s. Concern about the breast cancer risk associated with the high dose of stilbestrol used led to 2 follow-up studies of these clinical trial participants, as well as 2 other retrospective cohort studies to examine the subsequent risk of breast cancer in DES-exposed women. 3 of the 4 studies reported positive results, with an overall 50% increase in risk for ever using DES during pregnancy and an apparent latency period of more than 20 years. These studies have or more limitations, including the absence of information on dosage taken and duration of use, confusion about the identify of the exposed group and the inability to distinguish between the effect of DES and the effect of indications for using DES. Nevertheless, the findings supported a possible association between DES and breast cancer risk. The 4 studies were published between 1980 and 1984 and included many women who had only recently entered the age period when breast cancer incidence is high. It is possible that the incidence of breast cancer associated with DES may increase with additional follow-up time. Prenatal influences on carcinogenesis have recently become of interest in the etiology of adult cancer, and, in particular, it has been proposed that increased estrogen levels during pregnancy might increase the probability of breast cancer in daughters. It has been demonstrated that DES use during pregnancy can influence the subsequent risk of clear cell adenocarcinoma in offspring, although the issue of whether DES might also influence the subsequent risk of breast cancer in daughters remains to be investigated.^ieng

Asunto(s)

Neoplasias de la Mama/inducido químicamente , Dietilestilbestrol/efectos adversos , Efectos Tardíos de la Exposición Prenatal , Femenino , Humanos , Embarazo

RESUMEN

PIP: From the 1940s to the early 1970s, diethylstilbestrol (DES), an oral, nonsteroidal synthetic estrogen, was prescribed by physicians to 2-6 million women in the US alone to prevent miscarriages. In 1970, and article documented the correlation between in utero DES exposure and development of a rare vaginal cancer, clear-cell adenocarcinoma. In 1971, US Federal Drug Administration banned the drug from use during pregnancy. Since then, controlled studies have proven that administration of DES was associated with increased spontaneous abortions, premature delivery, complications during delivery, and neonatal deaths. DES-exposed daughters in reproductive age faced increased rates of infertility, spontaneous abortion, ectopic pregnancy, and premature delivery. DES-exposed daughters may suffer more pelvic inflammatory disease and dysmenorrhea. A 1988 study related the infertility experience of 796 daughters born to mothers who took part in a double-blind, controlled study of DES use during pregnancy at a Chicago hospital in 1951 and 1952. In early 1986, primary infertility was reported by 33% of the DES-exposed daughters as opposed to 14% of the unexposed subjects. However, 81% of pregnant DES daughters have at least one full-term live birth. Uterine abnormalities including a T-shaped or hypoplastic cavity, a septate uterus, intrauterine adhesions, or irregular uterine margins were documented in 46% of the DES-exposed daughters with primary infertility. Vaginal adenosis is reported to occur in 30%-90% of DES-exposed daughters. Cervical hypoplasia and shortened cervical structure are the primary cervical abnormalities. In addition, for 10 years researchers have observed certain alterations in the immune systems of DES-exposed women. Most physicians recommend alternative birth control methods to oral contraceptives to avoid an additional exposure to synthetic estrogens.^ieng

Asunto(s)

Aborto Espontáneo , Cuello del Útero , Dietilestilbestrol , Trompas Uterinas , Inmunidad , Infertilidad , Jurisprudencia , Trabajo de Parto Prematuro , Resultado del Embarazo , Embarazo Ectópico , Útero , Neoplasias Vaginales , Américas , Biología , Países Desarrollados , Enfermedad , Sistema Endocrino , Estrógenos , Genitales , Genitales Femeninos , Hormonas , Neoplasias , América del Norte , Fisiología , Embarazo , Complicaciones del Embarazo , Reproducción , Estados Unidos , Sistema Urogenital

RESUMEN

PIP: Although concerns about a possible association between exposure to diethylstilbestrol (DES) in utero, use of combined oral contraceptives (OCs), and cervical/vaginal carcinoma have been largely allayed, many physicians remain cautious with DES daughters. Over 80% of the 621 physician respondents in a 1987 Contraceptive Technology Update survey indicated they would prescribe combined OCs for DES offspring, but half of them would require more frequent or more thorough follow-up than with their other OC patients. There are indications that areas of metaplasia in the vagina convert into a malignancy faster in DES-exposed women than in nonexposed patients. Of the 16% of physicians who said they would not prescribe OCs for a DES daughter, the majority indicated they would refer the patient to a specialist who would probably prescribe OCs. Only 1.5% said they considered DES exposure to be an absolute contraindication to OC use. Physicians generally indicated that they would move more quickly to perform a colposcopy on DES-exposed patients in the event of abnormal Pap findings. Others noted that more extensive follow-up on DES daughters may not be clinically essential but good policy from a medicolegal standpoint.^ieng

Asunto(s)

Anticoncepción , Anticonceptivos Femeninos , Anticonceptivos Orales Combinados , Anticonceptivos Orales , Recolección de Datos , Atención a la Salud , Dietilestilbestrol , Enfermedad , Servicios de Planificación Familiar , Personal de Salud , Hormonas , Neoplasias , Médicos , Sustancias para el Control de la Reproducción , Neoplasias del Cuello Uterino , Neoplasias Vaginales , Biología , Anticonceptivos , Sistema Endocrino , Estrógenos , Salud , Fisiología , Investigación , Muestreo

RESUMEN

A clinical review of the first 200 patients who attended the DES Referral Clinic at The Royal Women's Hospital, Melbourne, has been undertaken. To date, clear-cell adenocarcinoma has not been detected in patients attending the Clinic. Fifteen per cent of patients who allegedly were exposed in utero to diethylstilboestrol (DES) showed no clinical stigmata. Vaginal adenosis was found in 41% of patients. On its own, cytological examination of vaginal smears was found to be unreliable as routine screening for detection of adenosis. Painting of the cervix and vagina with Lugol's iodine proved to be a more reliable screening test. Colposcopy is recommended in all patients who are suspected of having been exposed in utero to DES.

---

PIP: This paper presents the results of a review of the frequency of stigmata attributable to diethylstilbestrol (DES) exposure in the 1st 200 patients who attended the DES Referral Clinic at the Royal Women's Hospital in Melbourne, Australia. The value of cytological examination of vaginal and cervical smears as a screening method was also evaluated. Only 147 of the 200 patients were judged to have been exposed to DES. Of these, 22 (15%) had completely normal cytology findings and a normal vagina and cervix. There were no abnormal microscopic findings in an additional 31 patients (21%), although colposcopy revealed some atypical features in the transformation zone. The remaining 94 patients (64%) showed gross structural changes. Vaginal adenosis was present in 60 (41%) of the patients reviewed. There was complete correlation between the presence or absence of colposcopically detected vaginal adenosis and the presence or absence of glandular of metaplastic cells in the vaginal smears of 101 patients (69%). False positive results were obtained in 26 patients (18%) and false negative results occurred in 20 patients (13%). Painting of the cervix or vagina with Lugol's iodine was a more reliable screening test. No patients with clear-cell adenocarcinoma were detected in this series. It is recommended that, in cases of suspected DES exposure, the vagina and cervic should be carefully palpated and inspected, vaginal and cervical smears should be taken for cytologic examination, and Lugol's iodine should be applied to the vagina. Colposcopy, with biopsy of any suspicious areas, should also be performed.

Asunto(s)

Adenocarcinoma/etiología , Adenoma/etiología , Efectos Tardíos de la Exposición Prenatal , Neoplasias Vaginales/etiología , Adenocarcinoma/diagnóstico , Adenoma/diagnóstico , Colposcopía , Femenino , Humanos , Embarazo , Neoplasias Vaginales/diagnóstico

RESUMEN

Sequential examination and interview of diethylstilbestrol-exposed (DES-exposed) and -unexposed women verified that DES exposure has no effect on age at menarche and indicated no differences in the age at first coitus, pregnancy and live birth. Analysis of variance indicated that there is an age-related increase in oligomenorrhea in DES-exposed women as compared to unexposed women that disappears as the patients reach their late 20s. Prospective data collection is required to substantiate this finding. There appears to be no substantial effect of in utero exposure to DES on women's ability to conceive.

---

PIP: Sequential examination and interview of 349 women exposed to diethylstilbestrol (DES) and 375 women unexposed to the drug verified that DES exposure has no effect on age at menarche and indicated no differences in the age at 1st coitus, pregnancy, and live birth. Records of the women in the DES Adenosis project were studied to determine DES dosage and timing, but starting date and total amount prescribed could not always be determined accurately. Estimates indicate that about 1-2% of pregnant patients in the late 1950s and 1960s were exposed to the drug. As many as 30% of mothers were unaware that DES was given to them during pregnancy. The women were asked about marital status, age at menarche, menstrual history, pelvic inflammatory disease (PID), operations, birth control, and pregnancy experience. Analysis of variance indicated that there is an age-related increase in oligomenorrhea in DES-exposed women as compared to unexposed women that disappears as the patients reach their late 20s. Of 133 exposed women, 59 (44%) had induced abortions, and of 162 unexposed women 93 (57%) had induced abortions. DES-exposed women used oral contraceptives (OCs) but not as frequently or extensively as their unexposed counterparts. Age at first coitus was 19.33 +or-2.95 years for the exposed and 18.89 +or-2.62 years for the unexposed, showing no significant difference. In a higher percentage of DES-exposed women the cause of the couple's infertility was undetermined. 44 (12.6%) of the exposed and 42 (11.2%) of the unexposed women had dilatation and curettage (D and C) for some reason other than abortion. There appears to be no substantial effect of in utero exposure to DES on women's ability to conceive. Whether or not exposure to DES has specific physiological effects on reproductive function, exposed women may alter their sexual and reproductive behavior in anticipation of those effects as well as experiencing them.

Asunto(s)

Dietilestilbestrol/efectos adversos , Fertilidad/efectos de los fármacos , Menstruación/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal , Aborto Inducido , Adolescente , Adulto , Factores de Edad , Anticoncepción , Femenino , Humanos , Oligomenorrea/inducido químicamente , Paridad , Embarazo

RESUMEN

PIP: Both animal experimental work and epidemiological, clinical, and laboratory research on the effects of endogenous hormones in the human have made it clear that some influence of administered female sex hormones on the risk of certain cancers would be anticipated, and this has turned out to be the case. This review focuses on the administration of hormones during pregnancy, around the time of the menopause, and to prevent pregnancy. In the daughters who were exposed in utero to stilbestrol during the 1950s and 1960s, the most important effect is the development of clear cell adenocarcinoma of the vagina or cervix. Few cases of this disease have been reported before puberty, but the cumulative risk thereafter up to the age of 24 years is estimated to be between 1.4 and 4/10,000 exposed. Much less attention has been paid to the mothers who actually took the stilbestrol than to their daughters, but the published data fail to provide any convincing evidence of an increased risk of either breast or reporductive cancer among them. Regarding the administration of hormones around the time of menopause, it is well established that unopposed estrogen therapy in menopausal women can cause endometrial cancer. This has been demonstrated in a large number of case control studies reported since 1975. Most of these studies were conducted in the US and most concern the drup Premarin (conjugated equine estrogens). Some cohort studies also have been reported, and they largely support the results of the case control studies. There is now little doubt that combined oral contraceptives (OCs) protect against both epithelial ovarian cancer and endometrial cancer. Preliminary findings in the major cohort studies concerned with the longterm effects of OC use also are encouraging. A series of large case control studies conducted during the 1970s showed clearly that there is no general association between oral contraceptive use and breast cancer risk, but these large studies included few women with appreciable OC use at an early age and accordingly the publication by Pike et al. in 1981 caused much concern. Pike's study involved 163 women in Los Angeles County in whom breast cancer has been diagnosed at age 32 or less, together with a like number of neighborhood controls. Vessey et al. (1982) and the Centers for Disease control subsequently published results which did not support the California findings. Preliminary results from a new case control study conducted in Oxford and in London since 1980 suggest an increased risk of breast cancer in young women who have prolonged OC use before 1st pregnancy. The situation is very confusing and it may be some time before there is a conclusive answer. In a large cohort study conducted in Los Angeles, rates of progression from cervical dysplasia to carcinoma in situ were much higher in women using Ovulen than in women using IUDs.^ieng

Asunto(s)

Neoplasias de la Mama/inducido químicamente , Neoplasias de los Genitales Femeninos/inducido químicamente , Hormonas/efectos adversos , Adulto , Anciano , Anticonceptivos Orales/efectos adversos , Dietilestilbestrol/efectos adversos , Congéneres del Estradiol/efectos adversos , Femenino , Humanos , Menopausia , Persona de Mediana Edad , Embarazo , Riesgo

RESUMEN

Endometriosis was found in 39% and in utero diethylstilbestrol (DES) exposure in 5% of 397 infertile women who had undergone laparoscopy and/or laparotomy among 750 consecutively evaluated infertile couples. Fifty percent of the DES-exposed infertile women also had endometriosis, similar to the 39% with endometriosis among non-DES-exposed women. Cervical stenosis was found in 25% of all DES-exposed patients and in 83% of those who had undergone cryocautery or conization. However, 40% did not have endometriosis. Thus, while the frequency of endometriosis and cervical stenosis is extremely high in infertile women exposed in utero to DES, a significant association beyond that found in non-DES-exposed patients could not be established. Some of the infertility may be associated with cervical stenosis alone.

---

PIP: Endometriosis was found in 39% and in utero diethylstilbestrol (DES) exposure in 5% of 397 infertile women who had undergone laparoscopy and/or laparotomy among 750 consecutively evaluated infertile couples. 50% of the DES exposed infertile women also had endometriosis, similar to the 39% with endometriosis among non-DES exposed women. Cervical stenosis was found in 25% of all DES-exposed patients and in 83% of those who had undergone cryocautery or conization. However, 40% did not have endometriosis. Thus, while the frequency of endometriosis and cervical stenosis is extremely high in infertile women exposed to DES in utero, a significant association beyond that found in non-DES exposed women could not be established. Some infertility may be associated with cervical stenosis alone.

Asunto(s)

Dietilestilbestrol/efectos adversos , Endometriosis/inducido químicamente , Infertilidad Femenina/inducido químicamente , Efectos Tardíos de la Exposición Prenatal , Aborto Espontáneo/inducido químicamente , Endometriosis/diagnóstico , Femenino , Humanos , Laparoscopía , Laparotomía , Masculino , Embarazo

RESUMEN

PIP: This report reviews the results of various studies concerning the progeny of pregnant women exposed to diethylstilbestrol (DES), focusing on the effects on male and female progeny (lesions of the genital tract and reproductive performance). Studies concerning the DES effects on male progeny are few and involve small numbers of participants. The design of these studies attempts to show a relationship between structural abnormalities and/or infertility from DES exposure in utero. Driscoll and Taylor found that the ratio of interstitial cells to spermatogonia in the testicles of exposed male perinates was increased over that in controls. They also found squamous metaplasia rather than cuboidal tissue in the prostatic utricle. Structural abnormalities such as varicoceles and epididymal cysts were 8.9 times more common in DES exposed males than for nonexposed volunteers. Cryptorchidism and testicular hypoplasia have also been reported. Also cited in the literature are a decrease in sperm counts and in quality of sperm. Retrospective studies have shown that the incidence of clear cell adenocarcinoma of the vagina in exposed females is 0.14-1.4/1000 up to age 24. Approximately 2/3 of the 400 cases on registery from 1950 have been associated with exogenous estrogen use during the mother's pregnancy. The survival rate is 80% overall, and 90% if found at stage I. Observations of the vaginal and cervical epithelial changes found in DES exposed females appear in the literature from 1970 to the present. To data there is no increased risk of squamous cell cancer in these women. Several studies have noted that the amount of vaginal epithelial changes (VEC) observed in exposed women depended on the timing and the amount of drug given. These studies indicate that unless DES exposure was begun before the 18th week of gestation, the chance of VEC is very small. Sandburg et al. combined the results of pregnancy outcome studies from their institution with similar studies conducted elsewhere in an effort to isolate any difference in outcome of pregnancy between exposed and unexposed women. Their review included the following conclusions: approximately 25% of all pregnancies ended in elective abortion regardless of DES related history; the incidence of spontaneous abortion among exposed women is 24% versus 12% in the unexposed population; the incidence of preterm delivery was 3 times as great in the exposed population of women (approximately 16%); more than 2/3 of the exposed population had a least 1 pregnancy that ended with a term delivery; live births resulted in 67% of all pregnancies of exposed women in contrast to 87% in unexposed women; and 1 of every 24 exposed parous women will have at least 1 ectopic pregnancy and 1 of every 30 pregnancies in exposed women will be ectopic.^ieng

Asunto(s)

Dietilestilbestrol/efectos adversos , Efectos Tardíos de la Exposición Prenatal , Anomalías Inducidas por Medicamentos/etiología , Femenino , Genitales Masculinos/anomalías , Humanos , Infertilidad Masculina/etiología , Masculino , Embarazo , Complicaciones del Embarazo/etiología , Riesgo , Neoplasias Vaginales/etiología

RESUMEN

Squamous mucous membranes and squamous metaplastic epithelium sometimes undergo hypermaturation with the production of a keratin layer. Anucleated keratotic squamous plaques in smears are generally recognized as cytologic evidence of this altered maturation. This keratotic reaction was quantified in cytologic smears from 191 women exposed in utero to diethylstilbestrol (DES). Keratotic reaction was observed in the vaginal smear in 40% of the cases, in the cervical smear in 26% and in the endocervical smear in 19%; overall, a keratotic reaction was observed in at least one specimen from 48% of the women. These frequencies are higher than those reported in other studies. The observed frequency was age related. The significance of the hyperkeratosis, including its possible relationship to a lower dysplasia rate among DES-exposed women, is unclear. No conclusions can be drawn until more is known about behavioral factors in DES-exposed women.

---

PIP: Squamous mucus membranes and squamous metaplastic epithelium sometimes undergo hypermaturation with the production of a keratin layer. Anucleated keratotic squamous plaques in smears are generally recognized as cytologic evidence of this altered maturation. This keratotic reaction was quantified in cytologic smears from 191 women exposed to diethylstilbestrol (DES) in utero. Keratotic reaction was observed in the vaginal smears in 40% of the cases, in the cervical smear in 26%, and in the endocervical smear in 19%; overall, a keratotic reaction was observed in at least 1 specimen from 48% of the women. These frequencies are higher than those reported in other studies. The observed frequency was age related. The significance of the hyperkeratosis, including its possible relationship to a lower dysplasia rate among DES-exposed women, is not clear. No conclusions can be drawn until more is known about behavioral factors in DES-exposed women.

Asunto(s)

Dietilestilbestrol/efectos adversos , Queratosis/inducido químicamente , Adolescente , Adulto , Cuello del Útero/efectos de los fármacos , Cuello del Útero/patología , Epitelio/efectos de los fármacos , Epitelio/patología , Femenino , Humanos , Queratosis/patología , Metaplasia/inducido químicamente , Metaplasia/patología , Membrana Mucosa/efectos de los fármacos , Membrana Mucosa/patología , Vagina/efectos de los fármacos , Vagina/patología , Frotis Vaginal

RESUMEN

PIP: Soon after the reported association between diethylstilbestrol (DES) and clear-cell adenocarcinoma, large numbers of women exposed in utero to DES underwent screening examinations. Almost no cases of cancer were detected during this screening, but various epithelial abnormalities were found in many exposed women. Cervical and vaginal epithelial and structural abnormalities found in many DES-exposed women are described. Some of these abnormalities can be seen only with the aid of the colposcope, but many are visible to the naked eye. The identification of potentially exposed women should become a part of every physician's pelvic examination of women born since 1940. The 1st part of the examination of any DES-exposed women should be palpation of the vaginal vault with the index finger. This is done before speculum examination to identify any ridges, constrictions, or masses so that these can be visually inspected. Following vaginal palpation a bivalve speculum is introduced into the vagina in the routine fashion. At this point it is sometimes possible to observe a structural abnormality of the vagina and/or cervix. Any reddened area in the vagina or on the cervix is suspicious for the presence of glandular epithelium. Cytologic specimens should be obtained; it is important to sample all abnormal areas. Many DES-exposed women require sampling of the complete cervix, cervical side walls, vaginal fornices, and the vaginal vault to the point at which normal glycogenated squamous epithelium appears. The largest DES project in the US, "The DESAD Project," recommends taking 1 sample from the cervix wall and a separate sample from the vagina in those women who have vaginal abnormalities. These specimens should be handled in the usual way. It is recommended that whenever a cytologic sample from a DES-exposed woman is reported as being abnormal, the sample be sent to a DES center where it can be reviewed by a cytologist who has seen many samples from exposed women. Colposcopy has been a useful technique for the examination of DES-exposed women, but the findings are often confusing since many "abnormal" areas may be seen in women in whom no pathology is demonstrated. The 1st finding that will be seen by the colposcopist is a widened transformation zone. This may be located only on the cervix or may extend quite far into the vagina. When the glandular epithelium begins to mature, areas stimulating intraepithelial neoplasms may be seen. The areas of vaginal squamous metaplasia may mature with time.^ieng

Asunto(s)

Técnicas de Laboratorio Clínico , Diagnóstico , Dietilestilbestrol , Servicios de Planificación Familiar , Hormonas , Neoplasias , Sustancias para el Control de la Reproducción , Neoplasias del Cuello Uterino , Neoplasias Vaginales , Biología , Enfermedad , Sistema Endocrino , Estrógenos , Fisiología

RESUMEN

PIP: The Diethylstilbestrol Adenosis (DESAD) Project purpose is to study the frequency and natural history of genital tract changes in women exposed prenatally to diethylstilbestrol (DES). The intention is to update the medical community with current information on the health status of DES exposed persons, methods available for their identification, and plans for continuing examination and management. It is estimated that up to 6 million persons--mothers, daughters, and sons--were exposed to DES during its use for high risk pregnancy between 1940 and 1971. This risk of development of clear cell cancer is estimated to be no more than 1.4/1000 and possibly as few as 1.4/10,000 exposed daughters. By 1979, approximately 400 cases of this form of cancer were reported to the Registry for Research on Hormonal Transplacental Carcinogenesis from various parts of the world. Approximately 2/3 of these tumors were associated with intrauterine exposure to the nonsteroidal synthetic estrogen DES. Recent studies have indicated that DES exposed women may be at an increased risk for late pregnancy loss. Limited studies in males have shown no association between in utero DES exposure and cancer of the genitourinary tract. Mothers of the DES exposed daughters are also being studied. A practical method to alerting individuals about DES is for health care providers to display educational materials in their waiting rooms. Palpation is a crucial part of the DES examination and may provide the only evidence of clear cell adenocarcinoma. After palpation, a speculum of appropriate size is inserted. During the course of gross inspection, the speculum should be gently rotated as it is withdrawn in order to assess properly the entire length of the vagina. The secretions and epithelium in the upper 3rd of the vagina should be thoroughly sampled with a wood or plastic spatula, as should be the middle or lower 3rd of the vagina if gross epithelial changes are evident there. When an abnormal smear is reported, a physician may want to consult a gynecologist experienced in evaluating DES daughters. Colposcopy has not proved to be essential in the detection of clear cell adenocarcinoma. The order of gynecologic portion of examination of women exposed to DES in utero is as follows: vulvar inspection; vaginal and cervical palpation (digital); vaginal and cervical inspection (speculum); cytology (separate slides of vaginal fornices and cervix); colposcopy (optional); iodine stain of cervix and vagina; tissue biopsy of atypical findings; and bimanual (recto-vaginal) examination. Initial examination of known or suspected DES exposed females should be performed after menarche or by the age of 14 years if menarche has not occurred. The interval for follow-up examination is determined on an individual basis. The importance of education and counseling is identified and questions reflecting areas of concern to the DES exposed daughter are presented.^ieng

Asunto(s)

Adenocarcinoma/inducido químicamente , Dietilestilbestrol/efectos adversos , Efectos Tardíos de la Exposición Prenatal , Neoplasias Vaginales/inducido químicamente , Adenocarcinoma/diagnóstico , Adolescente , Adulto , Consejo , Femenino , Humanos , Masculino , Educación del Paciente como Asunto , Examen Físico/métodos , Embarazo , Riesgo , Neoplasias Vaginales/diagnóstico

RESUMEN

Two cases of vaginal clear-cell adenocarcinoma occurred as a result of maternal ingestion of diethylstilbestrol during pregnancy. The first case was diagnosed during the patient's first office visit. The second patient was first seen by the authors in 1976 and was followed at six-month intervals during the ensuing six years; the adenocarcinoma developed during this interval. Colposcopy and cytology were important in the diagnosis of both cases.

---

PIP: 2 cases of vaginal clear-cell adenocarcinoma, occurring as a result of maternal ingestion of diethylstilbestrol during pregnancy, are presented. The 1st case was diagnosed during the patient's 1st office visit, but the other patient's disease was diagnosed only after she had been followed regularly for 6 years. In utero exposure to diethylstilbestrol (DES) was documented during the 1st office visit of case 1. Medical records established that the 22-year old patient's mother had begun consuming Ensalstilbestrol, 25 mg daily, and increased the dosage to 25 mg t.i.d. during the 12th-14th week of gestation. She remained on this dosage throughout the pregnancy. 2 vaginal lesions were observed and examined colposcopically. A 1x1 cm mass on the right lateral vaginal wall was colsposcopically benign. A colposcopically directed biopsy of the posterior vaginal wall mass was performed, and histologic examination revealed a vaginal clear-cell adenocarcinoma. The patient had a clinical stage I cancer. Radical abdominal hysterectomy, periaortic node biopsy, bilateral pelvic lymphadenectomy, and total vaginectomy were performed. The resection margins and all lymph nodes were free of disease. A split thickness skin graft vaginoplasty was performed with 90-95% success. The mother of the 18-year old, nulliparous case 2 patient began injections of progesterone and DES at the time of her last menstrual period on February 18, 1956. The patient's physical examination on colposcopy clinic on May 29, 1975 was normal, but it soon became apparent that she was socially retarded and mentally slow. Pelvic examination on the 1st visit was not possible due to her inability to cooperate. Pelvic and colposcopic examination performed under general anesthesia 4 weeks later revealed gross and microscopic DES related changes. Colposcopically directed biopsies confirmed the diagnosis of vaginal adenosis and nabothian cysts. The cervix was also involved. The patient was examined colposcopically, and a Papanicolaou smear was performed approximately every 6 months. These smears were negative, and the colposcopic examinations were unchanged. The patient was hospitalized and again examined under anesthesia on December 8, 1978. Vaginal biopsies revealed vaginal adenosis and chronic inflammation. A Papanicolaou smear performed in 1980 showed focal endocervical cell atypia. On August 26, 1981 the patient was seen because of a vaginal discharge. A mass on the posterior wall was palpated on digital vaginal examination. Colposcopically directed biopsies confirmed the diagnosis of a clear-cell adenocarcinoma arising from the posterior vaginal wall ring. There was no evidence of cancer elsewhere in the vagina or on the cervix. On September 10, 1981 a radical abdominal hysterectomy, bilateral pelvic lymphadenectomy, periaortic node biopsy, and total vaginectomy were performed. The patient was treated wiht 5000 rads to an 8x10 cm midpelvic field, but vaginal reconstruction was not performed due to the patient's asocial lifestyle. An incidence of 0.14-1.4 tumors/1000 DES exposed females through age 24 is generally accepted.

Asunto(s)

Adenocarcinoma/patología , Dietilestilbestrol/efectos adversos , Efectos Tardíos de la Exposición Prenatal , Neoplasias Vaginales/patología , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirugía , Adolescente , Adulto , Colposcopía , Dietilestilbestrol/administración & dosificación , Femenino , Humanos , Prueba de Papanicolaou , Embarazo , Pronóstico , Neoplasias Vaginales/diagnóstico , Frotis Vaginal

RESUMEN

PIP: One consequence of vaginal adenocarcinoma in adolescents is the loss of reproductive potential. This report describes total removal of the vagina and of the vaginal portion of the cervix with an attached strip of bladder wall, together with bilateral extraperitoneal pelvic lymph adenectomy which allows preservation of reproductive potential. The woman, age 23, had had intrauterine exposure to stilbestrol and ethisterone. 2 factors affect the management of such cases: 1) removal of the primary tumor must be geographically clear in 3 dimensions, and 2) the incidence of pelvic lymph node metastasis is greater than that of comparable squamous cell lesions, indicating a need for lymphadenectomy. In this case menstruation was suppressed by medroxyprogesterone injection. Follow-up for a number of years is needed.^ieng

Asunto(s)

Adenocarcinoma/cirugía , Dietilestilbestrol/efectos adversos , Efectos Tardíos de la Exposición Prenatal , Neoplasias Vaginales/cirugía , Adenocarcinoma/inducido químicamente , Adulto , Femenino , Humanos , Métodos , Embarazo , Neoplasias Vaginales/inducido químicamente

RESUMEN

Seventy-nine patients with history and physical findings characteristic of antenatal DES exposure were randomly divided into two groups. Fourty-four DES-exposed offspring had their vaginal adenosis treated with the carbon dioxide laser (group I), and the remaining 35 DES-exposed offspring (group II) did not receive any specific treatment for this condition. Additionally, the 79 DES-exposed offspring were compared to an age-matched control population (group III). Treatment of vaginal adenosis with the carbon dioxide laser did not significantly reduce the incidence of development of new dysplasia in the DES-exposed offspring. This study also showed no statistical difference (p less than or equal to 0.05) in the incidence of dysplasia in DES-exposed offspring as compared to a control population.

Asunto(s)

Adenocarcinoma/inducido químicamente , Dietilestilbestrol/efectos adversos , Terapia por Láser , Lesiones Precancerosas/inducido químicamente , Neoplasias Vaginales/inducido químicamente , Adenocarcinoma/cirugía , Adolescente , Adulto , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Lesiones Precancerosas/cirugía , Embarazo , Efectos Tardíos de la Exposición Prenatal , Neoplasias Vaginales/cirugía

RESUMEN

A case of a child with acute lymphoblastic leukemia (ALL) is reported. The child's mother was exposed to diethylstilbestrol (DES) in utero during the first two trimesters of pregnancy. Causal association for this child's leukemia could have resulted either from a maternal germ cell event or abnormal DES-induced intrauterine environment.

---

PIP: A case of acute lymphoblastic leukemia in a child whose mother was exposed to diethylstilbestrol (DES) in utero during the 1st 2 trimesters of pregnancy is reported, and possible etiologies are discussed. This is the 1st reported case of DES-associated leukemia in either exposed women or their offspring. 5 months before the index pregnancy, the case's mother had a class II Pap smear and cervical erosion which was treated with cryosurgical conization. The case further had a positive family history for cancer. Maternal DES exposure and subsequent leukemia in the child may be coincidental. However, it is hypothesized that the susceptible host mother could have had a DES-induced change in her germ cells, placing her offspring's cells in a genetically determined premalignant state. Alternatively, an early somatic change during embryogenesis or a later prenatal or postnatal event could have acted on the case's cells. It is further possible that the DES-induced abnormal uterine environment allowed the developing fetal cells to acquire a malignant change.

Asunto(s)

Dietilestilbestrol , Leucemia Linfoide/diagnóstico , Efectos Tardíos de la Exposición Prenatal , Adulto , Femenino , Humanos , Lactante , Leucemia Linfoide/etiología , Neoplasias/genética , Embarazo

RESUMEN

Exposure to diethylstilbestrol (DES) in utero is associated with adverse effects on the reproductive tract in male and female progeny. These effects include epididymal cysts, microphallus, cryptorchidism, and testicular hypoplasia in male subjects and adenosis, clear cell adenocarcinoma, and structural defects of the cervix, vagina, uterus, and fallopian tubes in female subjects. As these offspring have reached reproductive age, reports of adverse reproductive performance have been published, including still controversial reports of menstrual dysfunction and infertility. More well established are increased rates of spontaneous abortion, ectopic pregnancy, premature deliveries, and perinatal deaths, all contributing to an increase in overall adverse pregnancy outcome. Often there is correlation between the DES-associated anatomic abnormalities in the reproductive tract and the adverse reproductive performance. Altered male reproductive capacity is also suggested by diminished semen analyses and sperm penetration assays. A detailed review of these effects of in utero DES exposure is presented.

Asunto(s)

Dietilestilbestrol/efectos adversos , Feto/efectos de los fármacos , Genitales/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal , Reproducción/efectos de los fármacos , Aborto Espontáneo/inducido químicamente , Adenocarcinoma/inducido químicamente , Criptorquidismo/inducido químicamente , Quistes/inducido químicamente , Femenino , Genitales Femeninos/anomalías , Genitales Masculinos/anomalías , Humanos , Recién Nacido , Infertilidad Femenina/inducido químicamente , Infertilidad Masculina/inducido químicamente , Masculino , Intercambio Materno-Fetal/efectos de los fármacos , Trastornos de la Menstruación/inducido químicamente , Embarazo , Embarazo Ectópico/inducido químicamente , Enfermedades Testiculares/inducido químicamente , Neoplasias del Cuello Uterino/inducido químicamente

RESUMEN

PIP: Lower and upper genital tract abnormalities detected in a group of women exposed in utero to diethylstilbestrol (DES) are reported. Data are from the Baylor College of Medicine, which is 1 of 4 participating centers in a National Cancer Institute project studying the incidence of genital tract abnormalities and cancer in DES-exposed offspring. Patients were recruited through physician referral and record review or were walk-ins. Gross anatomic changes of the cervix were noted in 178 (33%) of the 537 women with documented DES exposure. The occurrence of these changes decreased significantly when DES exposure was after the 20th week of gestation. An earlier study by the author noted upper genital tract abnormalities in 185 (69%) of 267 DES-exposed women on whom hysterosalpingography (HSG) was performed. Abnormal x-ray findings included a T-shaped uterus with a small cavity in 57%, a T-shaped uterus alone in 19%, a small uterine cavity in 13%, a T-shaped uterus with a constriction ring in 13%, and constriction rings alone in 4%. Uterine changes were unrelated to age or the occurrence of prior pregnancy. An abnormal HSG was 4.5 times more likely in women with structural cervical changes, occurring most often in women with a small uterine cavity. 146 (82%) of 179 women with vaginal epithelial changes had abnormal x-ray findings. Women with vaginal changes were 5 times more likely to show abnormal x-ray results. A gradual decrease of abnormal x-ray findings was noted with increasing gestational week of beginning DES exposure. The poor pregnancy outcome noted in DES-exposed women is believed to be associated with structural, cervical, and uterine changes rather than with DES exposure per se. The author's analysis of 93 DES-exposed women revealed the following pregnancy outcome statistics for women with abnormal and normal x-rays respectively: term pregnancy, 29% and 50%; spontaneous abortion, 27% and 16%; ectopic pregnancy, 7% and 0; and never a term delivery, 54% and 34%. These figures underscore the need for careful observation of DES-exposed women during pregnancy.^ieng

Asunto(s)

Anomalías Inducidas por Medicamentos/etiología , Dietilestilbestrol/efectos adversos , Genitales Femeninos/anomalías , Efectos Tardíos de la Exposición Prenatal , Adulto , Cuello del Útero/anomalías , Femenino , Muerte Fetal/etiología , Humanos , Embarazo , Complicaciones del Embarazo/etiología , Vagina/anomalías

RESUMEN

PIP: Attention in this discussion of the management of the adolescent girl exposed "in utero" to diethylstilbestrol (DES) is directed to the following: history; scope of the problem; pathogenesis/embryology; management; future fertility; squamous cell carcinoma; and male factors. In the late 1940s and early 1950s, estrogen deficiency was thought to play a role in the high fetal death rate among pregnant diabetic women. DES was 1st used in diabetics and soon thereafter in patients who were threatening to miscarry, who had previous stillbirths, and previous spontaneous abortions. Estrogens were used by some physicians through the late 1960s. In 1970 Herbst and Scully reported 7 carcinomas of the vagina in young women. On careful review, it was found that the mothers of these young women with clear-cell cancer had been treated with DES at various stages of their pregnancies. Subsequent investigation led to the discovery of the condition of vaginal adenosis in many young women exposed "in utero" to DES. It is estimated that 80-90% of patients exposed to intrauterine DES will show gross and microscopic evidence of vaginal and cervical adenosis. It is now felt by most authorities that adenosis coexists with the clear-cell cancer rather than preceding the tumor. A clear-cell tumor registry has been established and, to date, over 400 cases have been registered. The age-range of DES-exposed clear-cell carcinoma is between 7 and 31 years of age. The care of a girl exposed to DES begins when the physician is informed that the patient's mother either received the medication or there was any possibility of such medication. If bleeding occurs before the menarche, the patient should be hospitalized and examined under anesthesia. In the women of menstrual age, management has been somewhat controversial. The use of the colposcope has allowed careful initial examination of the cervix and vagina as well as providing an excellent means of follow-up. The colposcope has been very helpful in delineating the changes caused by DES. There are numerous gross findings that represent adenosis. These include the cervical changes of the "cockscomb" or anterior cervical ridge or "hood," a cervix within a cervix, and a hermicervix. With the colposcope, the areas of adenosis are seen as grape-like projections which, on biopsy, represent columnar epithelium. Areas of metaplastic squamous tissue are easily identified. On occasion dysplasia can occur in areas of adenosis. Of equal importance is the digital examination of the vagina. At this time it is felt that adenosis requires no other treatment than observations. The treatment of clear-cell carcinoma of the vagina or cervix is best determined by a gynecologic oncologist. 80% of DES patients have had live births.^ieng

Asunto(s)

Dietilestilbestrol/efectos adversos , Efectos Tardíos de la Exposición Prenatal , Adenocarcinoma/inducido químicamente , Adenocarcinoma/diagnóstico , Adolescente , Carcinoma de Células Escamosas/inducido químicamente , Cuello del Útero/patología , Colposcopía , Femenino , Genitales Masculinos/anomalías , Humanos , Hiperplasia , Masculino , Embarazo , Neoplasias del Cuello Uterino/inducido químicamente , Neoplasias del Cuello Uterino/diagnóstico , Útero/anomalías , Neoplasias Vaginales/inducido químicamente , Neoplasias Vaginales/diagnóstico

Asunto(s)

Anomalías Inducidas por Medicamentos , Dietilestilbestrol/efectos adversos , Genitales Masculinos/anomalías , Femenino , Humanos , Masculino , Embarazo

Asunto(s)

Dietilestilbestrol/efectos adversos , Edad Gestacional , Intercambio Materno-Fetal , Neoplasias Vaginales/inducido químicamente , Adulto , Femenino , Humanos , Embarazo