SEARCH · PubMed Health

Results for “DIETHYLSTILBESTROL”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 685 records · Page 38Linked to original sources

PubMed1991

The effect of neonatal exposure to diethylstilbestrol, genistein, and zearalenone on pituitary responsiveness and sexually dimorphic nucleus volume in the castrated adult rat.

The neonatal hormone environment determines the sexually differentiated pattern of brain growth. Estrogens, derived from intracerebral aromatization of testosterone, promote male sexual central nervous system (CNS) development. Developing animals may also encounter estrogens from plant, fungal, and xenobiotic sources (environmental estrogens). The purpose of this study was to assess the effects of environmental estrogens on the physiology and morphology of the hypothalamus and pituitary. Neonatal rats received injections of either corn oil, 0.1 microgram diethylstilbestrol (DES), 100 micrograms genistein (G100), 1000 micrograms genistein (G1000), 100 micrograms zearalenone (Z100), or 1000 micrograms zearalenone (Z1000) on Days 1-10 of life and were castrated on Day 21. On Day 42, right heart catheters were placed, GnRH (50 ng/kg) was administered, and blood was sampled for LH at 0, 5, 10, 15, and 30 min. Females exposed neonatally to DES, G1000, Z100, and Z1000 showed significantly decreased pituitary responsiveness to GnRH, whereas G100 increased GnRH-induced LH secretion. Males exposed neonatally to G100 also showed increased pituitary response to GnRH, and the remaining estrogen-exposed groups of males exhibited either decreased tonic LH or attenuated GnRH-stimulated LH secretion. The animals were killed by decapitation on Day 49. Volumes of the sexually dimorphic nucleus of the preoptic area (SDN-POA) of the exposed groups were compared. In females, DES, G1000, and Z1000 increased SDN volume; Z100 and G100 had no effect. There was no difference in SDN size among the male groups. These data show that exposure to environmental estrogens early in development alters postpubertal pituitary response to GnRH and "androgenizes" the SDN-POA.

Animals↗

PubMed1992

Effects of diethylstilbestrol on rat granulosa cell and thecal/interstitial cell transforming growth factor-beta 2 mRNA expression in vivo: analysis by reverse transcription-polymerase chain reaction.

Recent studies indicate that reproductive hormones may stimulate target cell growth via the actions of growth factors. In this study, reverse transcription-polymerase chain reaction analysis was used to assess the effects of in vivo diethylstilbestrol (DES) treatment on granulosa cell (GC) and thecal-interstitial cell (TIC) transforming growth factor (TGF)-beta 2 mRNA expression. In response to DES, GC expression of TGF-beta 2 mRNA was stimulated approximately 6.8-fold. By contrast, DES did not significantly alter TIC expression of TGF-beta 2 mRNA. Data were normalized relative to glyceraldehyde-3-phosphate dehydrogenase mRNA levels, which were unaffected by DES. These results extend our earlier findings, which demonstrated that GC and TIC expression of TGF-beta 2 mRNA is regulated by gonadotropins in vitro, to include steroidal regulation in vivo of intraovarian growth factor expression. Collectively, the present study and previous results support the following concepts: 1) intraovarian TGF-beta 2 mRNA expression is regulated by both gonadotropins and steroids, and 2) GC and TIC expression of TGF-beta 2 mRNA are differentially regulated.

Animals↗

PubMed1993

Effect of neonatal diethylstilbestrol exposure on luteinizing hormone secretion following ketamine anesthesia and gonadotropin-releasing hormone in castrated postpubertal rats.

Neonatal diethylstilbestrol (DES) exposure diminishes pituitary responsiveness to GnRH in castrated postpubertal rats 4 h after placement of intra-atrial cannulae under ketamine anesthesia. Ketamine anesthesia has been reported to blunt the preovulatory LH surge in female rats and to decrease baseline LH levels in males immediately following administration, although its effect lasted less than 2 h. It is not known what impact ketamine has on baseline LH levels or on GnRH-stimulated LH release in estrogen-exposed castrated rats. This study was designed to determine 1) whether the changes in GnRH-induced LH secretion in DES-exposed castrated rats are partially attributable to a direct effect of ketamine; 2) the gender-specific effects of ketamine on LH secretion; and 3) the DES-dependent effects of ketamine on LH secretion. In this experiment we ascertained the effect of ketamine anesthesia for right heart cannulation on LH levels in male and female 42-day-old castrated rats that were exposed to either corn oil or DES (0.1 microgram/day) on Days 1 through 10 of life. LH secretion in DES-exposed animals increased, in contrast to that in control animals, immediately (< 10 min) after anesthesia and cannulation. Mean LH levels in DES-exposed females were lower than in controls before GnRH administration and were blunted following GnRH. While ketamine and catheterization were associated with decreased LH titer in males, the extent of that decrease was not dependent on exposure to DES. Both sexes and exposure groups achieved baseline catheter LH values by 4 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

PubMed1993

Effect of neonatal diethylstilbestrol exposure on volume of the sexually dimorphic nucleus of the preoptic area of the hypothalamus and pituitary responsiveness to gonadotropin-releasing hormone in female rats of known anogenital distance at birth.

The effects of neonatal diethylstilbestrol (DES) exposure on the volume of the sexually dimorphic nucleus of the preoptic area of the hypothalamus (SDN-POA) and on GnRH-stimulated LH secretion were investigated in castrated female rats of known anogenital distance (AGD) at birth. The AGD was measured in females on the day of birth, and 0.1 microgram DES or corn oil was injected from Days 1 through 10 of life. The volume of the SDN-POA was significantly larger in animals that had received DES than in those that had received corn oil. The largest SDN-POA volumes were seen in DES-treated animals that had long (> 1.4 mm) AGDs, and smallest volumes in corn oil-treated females that had short (< or = to 1.4 mm) AGDs. Within treatment groups, animals with longer AGDs had significantly larger SDN-POA volumes than those with short AGDs. Within AGD subgroups, the effect of DES was similar in that the percentage increase in SDN-POA volume was equivalent. Pituitary responsiveness to GnRH was greater in corn oil-treated females with long AGD than in similarly treated females with short AGD. DES treatment blunted LH secretion in both AGD subgroups, but the increased LH secretion was preserved in rats with long AGD. The results indicate that the individual effects of the postnatal environment depend on the androgenicity of the intrauterine microenvironment. Further, variations in the individual's response to potential environmental hazards may be predicted by antecedent intrauterine events.

Anal Canal↗

PubMed1996

In situ demonstration of germinal cell apoptosis during diethylstilbestrol-induced testis regression in adult male Syrian hamsters.

Testis regression was induced in male Syrian hamsters by chronic exposure to diethylstilbestrol (DES), and estradiol-17 beta agonist. Experimental groups (n = 4-5) were killed at increasing time intervals over a period of 6 mo after initiation of treatment. Apoptosis in testes was demonstrated by in situ analysis of DNA fragmentation. Cell proliferation was monitored by immunostaining nuclei of S-phase cells after pulse labeling with 5-bromo-2'-deoxyuridine. Levels of FSH and testosterone, measured by RIA fell rapidly in DES-treated hamsters. In parallel, testis weight and seminiferous tubule area underwent an 80% decrease during the first 2 wk of DES administration. The composition of seminiferous epithelium was also drastically affected by DES, since it became progressively confined to Sertoli cells, spermatogonia, and spermatocytes. Testis regression was associated with an important increase of apoptosis, which started 3 days after the beginning of DES administration. Apoptosis was still 10- to 50-fold higher than in control testes by the end of treatment; it affected primarily spermatocytes and, to a much lesser extent, spermatogonia. Cell proliferation was not inhibited by chronic DES administration. In conclusion, these data indicate that apoptosis can by itself account for estrogen-induced testis regression.

Animals↗

PubMed1998

Effects of neonatal administration of diethylstilbestrol in male hamsters: disruption of reproductive function in adults after apparently normal pubertal development.

Prenatal and neonatal exposure to natural and synthetic estrogens induces developmental abnormalities in the male and female reproductive systems in several species. In hamsters, a single injection of diethylstilbestrol (DES) on the day of birth induces teratogenic and neoplastic changes throughout the female reproductive tract, apparently via a direct mechanism. The present study investigated the extent and specificity of this phenomenon in the male reproductive system. Male golden hamsters received injections of DES or estradiol-17beta (E2; 100 microg/ animal) on the day of birth and were then killed at 42 (pubertal) and 90 (adults) days of age. Blood was collected for serum testosterone analysis, and the testes and accessory organs were weighed and examined histologically. At the pubertal stage, testicular and accessory organ weights plus serum testosterone levels were similar in untreated animals and in both groups of estrogen-treated animals. Also at the pubertal stage, initiation of spermatogenesis appeared normal in both groups of estrogen-treated animals. In contrast, 100% of the DES-treated animals (n = 22) but none of the E2-treated animals exhibited multiple lesions in the reproductive tract as adults. These DES-induced lesions included cryptorchidism with the testes attached to the abdominal wall, solid testicular tumors, multiple epididymal cysts, and involution of accessory organs. Spermatogenesis was disrupted in the seminiferous tubules, with no developing germ cells, and the interstitial cells were organized as a sheath around the dysfunctional tubules. The epididymis had an involuted epithelial layer with a preponderance of multi-nucleated cells, and seminal vesicle morphology was also abnormal. These DES-specific alterations were not accompanied by any significant change in circulating testosterone levels. We therefore conclude that 1) DES is much more potent that E2 as a neonatal endocrine disrupter in the male hamster, and 2) the DES-specific lesions in the adult male reproductive tract may represent a permanently altered androgen responsiveness in the affected target tissues.

Animals↗

PubMed1998

Abnormalities in functional development of the Sertoli cells in rats treated neonatally with diethylstilbestrol: a possible role for estrogens in Sertoli cell development.

Diethylstilbestrol (DES) was administered neonatally (Days 2-12; 10 microg on alternate days) to rats, and developmental changes in Sertoli cell function were evaluated at 18, 25, and 35 days of age and compared to those observed in rats administered a GnRH antagonist (GnRHa; Days 2 and 5; 10 mg/kg) or a vehicle (controls). DES and GnRHa treatments resulted in similar reductions in both Sertoli cell numbers (40% for DES, 48% for GnRHa) and suppression of testicular growth at 18 and 25 days, though by 35 days the suppression was more pronounced (p < 0.001) in DES-treated animals. Plasma FSH levels were suppressed markedly at 18 and 25 days, but not at 35 days, in GnRHa-treated rats, whereas in DES-treated rats the FSH levels were suppressed significantly only at 35 days. Both treatments suppressed plasma levels of inhibin B, though this was more pronounced (p < 0.05) in DES- than in GnRHa-treated rats. In controls, Sertoli cell immunoexpression of inhibin alpha, sulfated glycoprotein-1 (SGP-1), and androgen receptor (AR) increased in intensity and changed to an adult, stage-dependent pattern by 25 days. In GnRHa-treated rats these changes were reduced in intensity but were similar to those in controls at 35 days. In DES-treated rats, the increase in intensity and stage-dependent pattern of immunoexpression of inhibin alpha, SGP-1, and AR were virtually absent at 25 days but were present by 35 days. Germ cell volume per Sertoli cell was reduced in GnRHa- and DES-treated rats compared with controls at 18 and 25 days but was significantly greater (p < 0. 001) in DES- than in GnRHa-treated rats at 35 days. The proportion of apoptotic to viable germ cells was increased (p < 0.01) in GnRHa- and DES-treated rats compared with controls at 18 and 25 days; but at 35 days, values in GnRHa-treated rats had declined to control values whereas those for DES-treated rats remained 10-fold elevated (p < 0.001). In adulthood, testis weight and daily sperm production were reduced by 43% and 44%, respectively, in GnRHa-treated rats, but spermatogenesis was grossly normal. Comparable changes were observed in approximately 25% of DES-treated rats, but the majority exhibited > 60% reduction in testis weight with many Sertoli cell-only tubules and very low daily sperm production. Taken together, these data are interpreted as providing evidence for direct modulation of Sertoli cell (maturational) development by DES.

Aging↗

PubMed1999

Differential activity of diethylstilbestrol versus estradiol as neonatal endocrine disruptors in the female hamster (Mesocricetus auratus) reproductive tract.

The synthetic estrogen diethylstilbestrol (DES) is a potent neonatal endocrine disruptor in the hamster. To test the specificity of this phenomenon, newborn animals were treated with 100 microgram of either DES or the natural estrogen, estradiol-17beta (E2). Of the two, neonatal DES exposure caused greater morphological disruption throughout the female reproductive tract in prepubertal animals and in adults that either retained their ovaries or were ovariectomized and then given the same levels of chronic E2 stimulation. In the uterus, a characteristic histopathological profile, including enhancement of both hyperplastic and apoptotic activity, was initiated prepubertally and exclusively in the endometrial epithelial cell compartment from the neonatally DES-treated animals and then was promoted by E2 stimulation during adulthood. Interestingly, apoptotic activity was not detected in an area of endometrial epithelium that progressed to the neoplastic state in a DES-exposed animal. Lastly, chronic estrogen induction of lactoferrin was also restricted to the DES-exposed endometrium. We conclude that 1) DES is more active than E2 as a perinatal endocrine disruptor in the hamster and 2) this experimental system should be generally useful as a means to screen compounds for such activity and then probe their mechanism of action.

Aging↗

PubMed2001

Diethylstilbestrol-treated adult rats with altered epididymal sperm numbers and sperm motility parameters, but without alterations in sperm production and sperm morphology.

In this study, we characterized estrogenic effects of diethylstilbestrol (DES) on reproductive parameters in male rats to identify a minimal dose level that alters epididymal and sperm functions but has little or no effect on sperm production and/or spermatogenesis. Adult rats (five animals/group) received s.c. injections of 0.2 ml of corn oil containing DES at a rate of 1.0 mg, 200 microg, 40 microg, 8 microg, 1.6 microg, or 320 ng x rat(-1) x day(-1) for 12 days. The control group received corn oil only. DES effects were similar in the 8-microg group and higher dose groups and included significant (P < or = 0.05) reductions in 1) absolute and relative weights of the head and body of the epididymis (EP), tail of the EP, and seminal vesicle, 2) numbers of sperm in both regions of the EP, and 3) motility characteristics in sperm collected from the tail of the EP. Conversely, no significant changes were observed in relative testis weight, daily sperm production, spermatogenesis, seminiferous epithelial height in stage VII, and sperm morphology. All of the above parameters in the 1.6-microg group (except seminal vesicle weight) and 320-ng group were comparable to those of controls. Plasma testosterone (T) level was reduced to an almost undetectable level in the > or = 8-microg groups and to a very low level in the 1.6-microg group (0.35 vs. 2.36 ng/ml in controls or 320-ng group), but LH level was unaltered. In a parallel fertility study, males received DES at a rate of 40, 8, or 1.6 microg x rat(-1) x day(-1) for 12 days prior to and 12 days during cohabitation (1:1) with untreated females. Of the 15 females cohabited with treated males (5 females/dose), none in the 40-microg and 8-microg groups and 1 in the 1.6-microg group formed a copulatory plug and delivered 8 pups, in contrast to 5/5 copulatory plugs and 13-15 pups/litter in the controls. DES at a rate of 8 microg x rat(-1) x day(-1) for 12 days reduced EP weights, sperm numbers in the EP, and sperm motility patterns but caused minimal to no alterations in daily sperm production, spermatogenesis, or sperm morphology. Factors other than T, or in addition to lower T, may be responsible for DES-induced reproductive disorders (despite lower T, sperm contents and sperm motility patterns in the EP were normal in the 1.6-microg group). Deficits in EP sperm functions and/or sexual behavior (as evident from absence of copulatory plugs) probably accounted for reduced fertility in treated males.

Animals↗

PubMed2000

In utero diethylstilbestrol (DES) exposure alters Hox gene expression in the developing müllerian system.

Diethylstilbestrol (DES) was widely used to treat pregnant women through 1971. The reproductive tracts of their female offspring exposed to DES in utero are characterized by anatomic abnormalities. Here we show that DES administered to mice in utero produces changes in the expression pattern of several Hox genes that are involved in patterning of the reproductive tract. DES produces posterior shifts in Hox gene expression and homeotic anterior transformations of the reproductive tract. In human uterine or cervical cell cultures, DES induces HOXA9 or HOXA10 gene expression, respectively, to levels approximately twofold that induced by estradiol. The DES-induced expression is not inhibited by cyclohexamide. Estrogens are novel morphogens that directly regulate the expression pattern of posterior Hox genes in a manner analogous to retinoic acid regulation of anterior Hox genes. Alterations in HOX gene expression are a molecular mechanism by which DES affects reproductive tract development. Changes in Hox gene expression are a potential marker for the effects of in utero drug use that may become apparent only at late stages of development.

Animals↗

PubMed1986

Estramustine phosphate compared with diethylstilbestrol. A randomized, double-blind, crossover trial for stage D prostate cancer.

In a double-blind, crossover comparison, 236 patients with metastatic prostate cancer were randomized to receive estramustine phosphate (EMP) or diethylstilbestrol (DES). Previously castrated patients (66) were separately randomized. Patients kept taking their first drug until progression was proved by objective studies, at which time alternative treatment was begun. The primary determinant of efficacy was the duration between start of therapy and date of objective progression. Uncastrated patients treated with EMP had a significantly longer duration without progression than those treated with DES (p less than 0.01). The following subcategories of entry were further evaluated: little or no pain, moderate to severe pain, little reduction in activity, significant reduction in activity, presence or absence of cardiovascular disease, age above or below 70 years, and "good" or "bad" histology. For all but the last category, EMP was statistically superior to DES. Patients who underwent orchiectomy less than 3 months before randomization had nonprogression rates similar to those for noncastrated men in both groups. Secondary (crossover) therapy was less effective than first therapy in both groups: 46% of patients receiving EMP and 40% receiving DES had no progression at 6 months. Clinical and laboratory adverse experiences were similar for both drugs, except that gastrointestinal disturbances were more common in the EMP group.

Clinical Trials as Topic↗

PubMed1988

Simultaneous administration of a luteinizing hormone releasing hormone agonist and diethylstilbestrol in the initial treatment of prostatic cancer.

It is well known that the first administration of luteinizing hormone releasing hormone (LH-RH) analogues induces an initial increase of luteinizing hormone (LH) release and a subsequent rise in testosterone (T). This rise is maximal after 3-4 days and is followed by a steady fall of LH and T. Several investigators have reported flare-up symptoms in patients with advanced prostatic cancer, associated with the rise of T, when treated by LH-RH analogue alone. In order to prevent these flare-up symptoms, we treated 20 patients with advanced prostatic cancer with an association of a LH-RH analogue (Zoladex Depot) and diethylstilbestrol (DES) 1 mg/day. DES was given for 14 days, starting 7 days before the first Zoladex Depot injection. T fell to near castrate levels within a few days, but rose again 3-4 days after the administration of the LH-RH analogue to pretreatment values before returning to castrate levels. No clinical flare-up manifestations were recorded. We conclude that combination treatment with DES can prevent the flare-up symptoms induced by LH-RH analogue in patients with prostatic cancer.

Aged↗

PubMed1988

Interim report of a randomized trial comparing Zoladex 3.6 mg depot with diethylstilbestrol 3 mg/day in advanced prostate cancer. The West Midlands Urology Research Group.

A study comparing Zoladex 3.6 mg depot with diethylstilbestrol (DES) 3 mg/day was initiated in August 1985. One hundred ninety-three patients with histologically confirmed prostate cancer T3/4 or M1 have been randomized up to 31 March 1987: 95 to Zoladex, 98 to DES. No patient had received prior systemic therapy. There is no bias in the treatment groups in terms of baseline characteristics. Median follow-up is 11 months, and the response rate at 12 months from randomization (CR + PR) for Zoladex is 70 +/- 9.4% and 50 +/- 10.1% for DES. Median time to best response is 6 months for Zoladex and 12 months for DES (using the Kaplan-Meier life table method). Subjective responses are 56 +/- 10.2% for Zoladex and 44 +/- 10% for DES. Five increases in bone pain were found after the first Zoladex treatment, as well as one increased ureteric obstruction. None required treatment withdrawal. Seventeen patients on DES were withdrawn due to adverse reaction (chi 2 = 4.33, 1df, p less than 0.05). Overall survival at 31 March 1987 is 84% for the Zoladex group and 78% for the DES group. This study has shown that Zoladex is superior to DES in achieving early tumor response in advanced prostate cancer, without causing serious complications warranting withdrawal of treatment.

Buserelin↗

PubMed1986

Diethylstilbestrol-associated vaginal adenosis followed by clear cell adenocarcinoma.

A young woman was examined because of a history of in utero exposure to diethylstilbestrol and was identified as having vaginal adenosis. Fourteen months later, on routine follow-up, a small vaginal clear cell adenocarcinoma was recognized. She refused any therapy other than wide local excision. She was seen intermittently for several years with no recurrence. Five and one-half years after initial diagnosis she was found to have multiple sites of clear cell adenocarcinoma in the upper third of the lateral and anterior vaginal walls. Cases of vaginal adenosis followed later by the development of clear cell adenocarcinoma (metachronous cases) are distinctly unusual. The authors have collected the other recorded cases in the literature or in the Registry for Research on Hormonal Transplacental Carcinogenesis and have attempted to compare these cases with the larger group of patients who present with clear cell adenocarcinoma and have associated vaginal adenosis (synchronous cases). The authors have found few differences between the two groups. Most of the differences can be accounted for by the close follow-up of patients with known vaginal adenosis. However, it has been noted that the location of the clear cell adenocarcinoma is apparently different in the two groups. The reasons for this apparent difference are briefly discussed.

Adenocarcinoma↗

PubMed1991

Gender-related behavior development in females exposed to diethylstilbestrol (DES) in utero: an attempted replication.

This report concerns the role of prenatal hormones in normal and abnormal psychosexual differentiation. Several studies indicate that perinatal treatment of infrahuman female mammals with diethylstilbestrol (DES) masculinizes certain features of their brain and behavior. Accordingly, the authors have hypothesized that prenatal exposure to DES may also masculinize the gender-role behavior of girls and women. A previous study suggested that prenatally DES-exposed women show decreased interest in parenting. The authors failed to replicate these findings in a different sample despite the use of similar methodology. Post-hoc analysis shows that the assessment devices would have detected masculinization if it were present. The implications of these findings for an understanding of psychosexual development are discussed.

Adolescent↗

PubMed1978

Design and preliminary observations of National Cooperative Diethylstilbestrol Adenosis (DESAD) Project.

The National Cooperative Diethylstilbestrol Adenosis (DESAD) Project has completed the major portion of its enrollment phase with the examination of more than 3000 daughters of women taking synthetic nonsteroidal estrogens (denoted DES) during pregnancies occurring from the early 1940s to the mid-1960s. The aims of the Project are to fill urgent needs for information on the prevalence and incidence of structural and epithelial abnormalities or neoplastic changes and their complications in these young women. Participants are grouped by mode of entry as identified by prenatal record review (40.1%), documented as DES-exposed but walking in (25.1%), or referred (22.8%) to the DESAD Project for examination, and not documented as exposed but having gynecologic abnormalities typical of those associated with DES exposure (12.0%). This study cohort, in part having paired controls, will be examined annually for at least 5 years. Details of the design and selected preliminary findings are reported.

Adolescent↗

PubMed1978

Squamous cell dysplasia and carcinoma in situ of the cervix and vagina after prenatal exposure to diethylstilbestrol.

Squamous cell abnormalities of the vagina and cervix were evaluated in 1424 women exposed to diethylstilbestrol (DES) in utero. The prevalence of dysplasia was 2.1% and the incidence 0.85/100 person-years of followup. The dysplastic epithelial changes were almost always mild in women with no prior history of dysplasia and was slightly more frequent in the cervix than the vagina. Severe dysplasia and carcinoma in situ (CIS) were encountered only in those subjects specifically referred because of those abnormalities. The most common problem in the diagnosis of these squamous cell changes was the misinterpretation of mature and immature metaplastic cells for dysplastic squamous cells. Discordance between biopsy and cytology was common-place in the detection and followup of dysplasia, especially when it was mild. There were no instances in the study where cytology and biopsy samples from the vagina were both abnormal concurrently. Colposcopically directed biopsies did not increase the frequency of confirmation of cytologic findings. These data suggest that both cytology and biopsy of abnormal segments of the vagina and cervix remain an integral part of the examination of the DES-exposed female during long-term follow-up studies.

Adolescent↗

PubMed1990

Antepartum and intrapartum events in women exposed in utero to diethylstilbestrol.

Using a retrospective cohort design, we analyzed the effects of intrauterine diethylstilbestrol (DES) exposure on various antepartum and intrapartum events. Gravidas exposed to DES had a higher likelihood of being delivered abdominally, undergoing manual removal of the placenta, and hemorrhaging in the postpartum period. The increased risk for these events remained after controlling for age, race, and parity. We also constructed labor curves in DES-exposed women by plotting cervical dilation against time. The curves were similar for nulliparous DES-exposed women and nulliparous controls, but DES-exposed parous women experienced prolonged labors. These findings suggest that, in addition to the well-known adverse effects of intrauterine DES exposure, the interaction between the uterus and placenta is altered in some DES-exposed patients.

Adult↗