Sexual activity level and sexual functioning in women prenatally exposed to diethylstilbestrol

Could DES Daughters have difficulties in sexual desire and enjoyment?

1985 Study Abstract

Thirty women with a history of prenatal exposure to diethylstilbestrol (DES) underwent a detailed sexual history and were compared to a demographically similar sample of 30 women with a history of an abnormal Pap smear.

Sexual activity level and sexual functioning in women prenatally exposed to diethylstilbestrol, US National Library of Medicine, Psychosomatic medicine, NCBI PubMed PMID: 4070521, 1985 Nov-Dec.

Image credit Helen Taylor.

The DES women were found to have less well-established sex-partner relationships and less experience with child-bearing, to be lower in sexual desire and enjoyment, sexual excitability, and orgasmic coital functioning, but to be comparable (and low) with regard to such sexual dysfunctions as vaginismus and dyspareunia.

Both potential psychosocial and neuroendocrine explanations are discussed.

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Sexual orientation after prenatal exposure to Diethylstilbestrol

Sexual orientation image

DES Daughters tend to show increased bisexuality and homosexuality

Abstract

Thirty women aged 17 to 30 years with documented prenatal exposure to the nonsteroidal synthetic estrogen diethylstilbestrol (DES) were compared to thirty women of similar demographic characteristics from the same medical clinic who had a history of abnormal Pap smear findings.

Sexual orientation after prenatal exposure to exogenous estrogen, US National Library of Medicine, Archives of sexual behavior, NCBI PubMed PMID: 3977584, 1985 Feb.

Image credit gazeronly.

A subsample of the DES women were also compared to their DES-unexposed sisters. Sexual orientation in its multiple components was assessed by systematic semistructured interviews.

In comparison to both control groups, the DES women showed increased bisexuality and homosexuality. However, about 75% of the DES women were exclusively or nearly exclusively heterosexual.

Nonhormonal and hormonal interpretations of these findings are discussed.

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Management of DES-Exposed Patients : Psychological Support

Screening and Management of Diethylstilbestrol Exposed Offspring

Summary

Prenatal diethylstilbestrol (DES) exposure in pregnancy has been associated with adenocarcinoma of the vagina and/or cervix as well as teratogenic abnormalities of the genital tract in both female and male offspring. DES Action groups are alerting the public to the dangers inherent in being a `DES daughter‘ or a `DES son‘. Family physicians must be able to reassure those patients who are not DES offspring, manage those who are, and detect those who didn’t know they were. The screening and management of DES problems, including history-taking, physical examination, relevant laboratory exams and consultation for diagnosis and treatment of both male and female patients are discussed. In addition, psychological support, patient education, longterm follow up, the management of contraception and pregnancy in DES daughters, and infertility in DES sons are considered.

Management Of DES-Exposed Male Patients : Psychological Support

Screening and Management of Diethylstilbestrol Exposed Offspring, US National Library of Medicine, National Institutes of Health, The College of Family Physicians of Canada, NCBI PubMed PMC2153721, 1984 Aug; 30.

Image credit movimente.

Helping families cope with DES-induced abnormality and pathology involves dealing with the family’s and patient’s anger at the medical profession for having led them into this situation. The family doctor has to function in an agonized setting where the cardinal rule ‘first do no harm‘ has been violated.

It also involves helping assuage the mother’s guilt at having collaborated in a treatment which has brought hazard or harm to her children. She must be made to understand that the responsibility rests with the medical profession, one of whose members prescribed a treatment that was generally considered appropriate at the time. A good support for the patient and family is DES Action Groups which provide information and readily available self-help groups.

Where genital abnormality or genital surgery has led to sexual problems, the family physician may have to refer the patient to sexual counsellors and therapists with experience in sexual therapy and rehabilitation.

Conclusion

The seventeenth-century philosopher, Rene Descartes, called medicine “a science that was forced into practice too early“. Implications in some articles we have read in the public press are that doctors gave DES to pregnant women out of some combination of callousness, stupidity and monetary greed. In fact, doctors gave DES to pregnant women who were likely to suffer a spontaneous abortion because it was believed DES might prevent miscarriage.

In retrospect, however, it is important to try and understand why doubleblind studies done in the early 1950s, concluding that DES was ineffectual in maintaining pregnancies at risk, were largely ignored. One answer seems to be that physicians as a group rely too heavily on the pharmaceutical industry’s advertising and not firmly enough on objective research in evaluating the medications we use. The medical profession’s tragic experience with DES should lead us to constantly examine the process of drug evaluation and take steps to control the pharmaceutical industry’s influence on evaluative trials and the dissemination of drug information.

Reading the DES Action literature, one sees, understandably, a lot of anger towards the medical profession. However, despite this background of bitterness, one frequently hears DES patients’ unqualified expressions of appreciation and admiration for the doctors who are presently caring for them.

It is incumbent upon us not to neglect the detection and treatment of DES-induced abnormality and disease. The tools for this task are continual attention to the facts of DES-induced disease as they continue to emerge, and the two basic maneuvers of sound medicine: a good history and a thorough physical examination.

Michael Malus, Alex Ferenczy, 1984.

Download the full paper on NCBI.

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Depression and anxiety doubled in the DES-exposed offspring

A randomized double-blind controlled trial of the value of stilboestrol therapy in pregnancy: long-term follow-up of mothers and their offspring

Abstract

In the early 1950s, a randomized, double-blind, controlled trial of the value of prophylactic stilboestrol therapy given antenatally to reduce the incidence of late pregnancy toxaemia and to improve perinatal mortality was conducted at University College Hospital, London.

A randomized double-blind controlled trial of the value of stilboestrol therapy in pregnancy: long-term follow-up of mothers and their offspring, US National Library of Medicine National Institutes of Health, British journal of obstetrics and gynaecology, NCBI PubMed PMID: 6357269, 1983 Nov.

Image credit neilmoralee.

Women expecting their first baby were allocated to one or other of two groups. Those in the stilboestrol group started treatment at the 12th week of pregnancy on average and received a mean dose of about 11.5 g of the drug while those in the control group received placebo tablets.

In spite of the fact that the original trial documentation was lost, it was possible to be fairly certain which was the treated group and follow-up data from 650 mothers and 660 offspring were obtained from death certificates, cancer registrations and questionnaires sent to general practitioners.

We found no indication of any harmful long-term effect of stilboestrol exposure during pregnancy on the mothers–in particular 10 out of 331 women in the untreated group and 9 out of 319 women in the treated group were found to have developed breast cancer.

Amongst the daughters, those in the treated group suffered an excess of minor benign lesions of the cervix uteri and an excess (not statistically significant) of unfavourable pregnancy outcomes. None of the daughters had developed clear cell adenocarcinoma of the vagina or cervix uteri.

Amongst the sons, we discovered no evidence of any significant excess of genital tract disorders or of impaired reproductive performance in the treated group but one son developed a (fatal) teratoma of the testis.

Unexpectedly, psychiatric disease (especially depression and anxiety) was reported by general practitioners about twice as often in the treated group offspring (sons and daughters) as in the untreated group. This result cannot be due to bias, and is unlikely to be due to confounding or chance, and may thus represent an adverse effect of exposure to stilboestrol in utero.

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Observations on the psychological impact of diethylstilbestrol exposure and suggestions on management

Physicians can help the DES-exposed deal with their emotional issues

Abstract

The emotional impact of diethylstilbestrol (DES) exposure is described in a series of 50 mothers and daughters interviewed by psychiatrists. Patterns of response to this trauma and methods of resolution are discussed, and opportunities for preventive intervention by gynecologists are suggested. Specific, open dialogue about DES with the patient as a colleage can minimize the emotional sequelae of the experience.

PIP:

Observations on the psychological impact of diethylstilbestrol exposure and suggestions on management, US National Library of Medicine National Institutes of Health, The Journal of reproductive medicine, NCBI PubMed PMID: 7373597, 1980 Mar.

Image credit theloushe.

This study analyzes the emotional impact of diethylstilbestrol (DES) exposure in an index population consisting of 50 women at risk plus 30 mothers who were all interviewed about their DES experience in an open-ended, in-depth, clinical style. The findings show that significant emotional upset is the normal response to the knowledge that the ingestion of a drug during pregnancy can cause or has caused some abnormality in the offspring.

Nevertheless, the capacity of a woman to come to terms with the anxiety DES has generated, once she had been given the chance to express her feelings and fears, was impressive.

DES daughters reacted to the DES experience in one of 3 ways, in descending order of frequency:

  1. trust (80%). Most DES daughters rationalized that their mothers and doctors did the best they could, and were generally cooperative in their follow-up care;
  2. hostility (10%);
  3. and fear (10%).

90% of DES mothers came to terms with the knowledge and implications of DES exposure in ways characteristic of their life-long personality styles; in contrast, the remaining 10% who did not come to terms with the reality of DES exposure felt overwhelmed by quilt, paranoid rage, fear, and despair.

Physicians can help patients deal with such problems by:

  1. acknowledging problematical feelings and expecting them to be difficult to deal with;
  2. noting the patient’s pattern of response, and supporting her strengths;
  3. giving factural information matter-of-factly;
  4. listening to reactions to this information;
  5. giving a structured plan in which the woman participates and be available for follow-through on it (eg, periodic colposcopic examinations);
  6. and referring the women to support groups for an extended network of information and continued support.
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Prenatal “female hormone” administration and psychosexual development in human males

Males were exposed to diethylstilbestrol (DES) and/or to natural or synthetic progesterone

One of the first primary studies of DES sons which focused on their behavioral development , this study explored the hypothesis that prenatal DES exposure in males has feminizing effects.

Abstract

Considerable data exist from animal research relating prenatal hormone levels to postnatal behaviors in the male. The data from human males are few. One strategy for testing this association is the study of humans exposed prenatally to exogenous ‘pregnancy maintaining hormones’.

Prenatal ‘female hormone’ administration and psychosexual development in human males, Psychoneuroendocrinology, Volume 5, Issue 4, 1980, Pages 269–285, dx.doi.org/10.1016/0306-4530(80)90032-3, 1980.

Phallic Symbol credit Carol Fraser © all rights reserved.

Fifty-eight young adult males exposed to one of four hormone regimens were matched against nonhormone exposed controls. There were 17 males exposed to diethylstilbestrol (DES), 22 exposed to DES and natural progesterone, 10 to natural progesterone only, and 13 to synthetic progesterone.

Subjects were interviewed for various aspects of psychosexual development, and administered the Bem Sex-Role Inventory (BSRI), the Guilford-Zimmerman Temperament Survey (GZTS), the Strong Vocational Interest Blank (SVIB), and the Embedded Figures Test (EFT).

Drug, total dosage, and time of drug administration were significantly associated with several aspects of boyhood, adolescent, and adult psychosexual development on interview and with differences in scales of the psychometric tests.

The most contrasting boyhood behaviors were between those exposed to progesterone and DES. Progesterone subjects tended to recall boyhood behaviors which departed from the conventional male mode toward ‘femininity’. The DES subjects tended to recall the most conventionally ‘masculine’ boyhoods. During adulthood, DES plus natural progesterone subjects reported a high sex drive while synthetic progesterone subjects reported a low sex drive. Erectile failure was more often reported by subjects exposed to natural progesterone only.

Three drug regimens were associated with elevations of the Feminine scale of the BSRI and two with elevations of the feminine scale of the GZTS.

The rates of homosexual behavior were comparable for drug and non-drug-exposed subjects.

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Psychological Effects of Diethylstilbestrol Exposure

Guilt: the most common problem among DES mothers

Abstract

The psychological response of daughters and their mothers to discovery of in utero diethylstilbestrol (DES) exposure was studied.

At the DES Colposcopy Clinic, 41 daughters and 20 mothers were extensively interviewed. Twelve patients with abnormal cytology tests were controls.

Psychological effects of diethylstilbestrol exposure,  US National Library of Medicine National Institutes of Health,  JAMA, doi:10.1001/jama.1977.03270300056007, January 17, 1977.

Initial anxiety was usually followed by acceptance of the condition after examination and counseling. Patients responded best when informed of their problem by their mothers and when the relationship between mother and daughter was good.

The majority of patients found colposcopy to be unpleasant; they tended to be disturbed in proportion to the degree of being upset about DES exposure. The most common problem among mothers was guilt.

A questionnaire survey of physicians showed that they had less concern for psychological problems than patients or mothers did. Sensitivity and good communication on the part of medical personnel are recommended.

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DES gender-specific effects on weight gain, bone development

Neonatal exposure to Diethylstilbesterol exerted gender-specific effects on body weight gain and bone health

Abstract

Neonatal exposure to diethylstilbesterol (DES) in female mice programs estrogen-sensitive tissues, resulting in greater body weight gain and positive effects on bone architecture at adulthood.

Using the CD-1 mouse model, the objective of the present study was to examine how short-term neonatal exposure to DES modulates weight gain as well as bone mineral density (BMD), bone strength, and bone microarchitecture in both males and females at adulthood.

Diethylstilbesterol has gender-specific effects on weight gain and bone development in mice, US National Library of Medicine National Institutes of Health, Journal of toxicology and environmental health, NCBI PubMed PMID: 18569612, 2008.

Male and female offspring (n = 8-12 pups/treatment/gender) were randomized to DES (2 mg/kg bw/d) or control (corn oil) from postnatal day 1 to 5 (subcutaneous injection, once daily) and sacrificed at 4 mo of age. Body weight was measured weekly, while bone mineral, strength, and microarchitecture were measured at 4 mo of age.

DES treatment resulted in significantly higher body weight in females but lower weight in males at 4 mo of age. In DES-treated females, markedly higher BMD of lumbar vertebrae (LV1-LV3) was translated into significantly stronger LV2 that was more resistant to fracture; similar effects were observed at the femur midpoint. At the spine, males had a markedly lower BMD and peak load, suggesting an adverse effect. Microstructural analyses demonstrated that functional changes in femurs, i.e., peak load, were primarily due to modulation of cortical bone.

In conclusion, neonatal exposure to DES exerted gender-specific effects on body weight gain and bone health.

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Effect of neonatal exposure to DES on pelvis and femur

image of pelvis and femur

Abstract

BACKGROUND
Permanent abnormalities have been reported in reproductive and non-reproductive organs of mice and humans exposed perinatally to a synthetic estrogen, diethylstilbestrol (DES). Recent studies demonstrated that sex hormones affected the shape of the innominate bone in mice. Therefore, we analyzed the long-term effects of neonatal exposure of DES and tamoxifen, an anti-estrogen, in mouse bones.

Effect of neonatal exposure to diethylstilbestrol and tamoxifen on pelvis and femur in male mice, Environmental Health Perspectives, NCBI PubMed PMC1518867, 1995 Oct.

METHODS
Changes in the pelvis and femur were examined in 1- to 15-month-old C57BL/Tw male mice given 5 daily injections of 3 micrograms DES or of 100 micrograms tamoxifen beginning on the day of birth by measuring contents of calcium (Ca) and phosphorus (P), and the numbers of osteoblasts and osteoclasts.

RESULTS
The ash weight of pelvis and femur in neonatally DES- and tamoxifen-treated mice was lower than that in the controls at 2-15 months of age. Contents of Ca and P of pelvis and femur in neonatally tamoxifen-treated mice were lower than in the controls and neonatally DES-treated mice. In neonatally DES-treated mice at 6-12 months, Ca and P contents in the pelvis were lower than in controls, but not different in the femur. The number of osteoblasts per unit length of endocortical surface of the femur in 2- and 3-month-old DES- and tamoxifen-treated mice was lower than that in the controls. The osteoclast number in the femur in DES-treated mice at 2 to 12 months was not different from that in the controls; however, in tamoxifen-treated mice, the number was higher than in the controls. An epiphyseal line was clearly detected in the femur of 12- and 15-month-old DES- and tamoxifen-treated male mice, whereas the line in the controls disappeared after 12 months.

CONCLUSIONS
The present results indicate that in male mice, neonatal exposure to DES and tamoxifen induced permanent changes in the pelvis and the femur, and that tamoxifen had a greater effect on bone tissue than did DES.

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Alterations in estrogen levels during development affects the skeleton: use of an animal model

Abstract

Exposure to estrogens during various stages of development has been shown to irreversibly influence responsive target organs. The recent finding of the presence of estrogen receptor in both osteoblasts and osteoclasts has suggested a direct role of steroid hormones on bone tissue. Furthermore, estrogens have important effects on bone turnover in both humans and experimental animal models. Thus,  this tissue is now regarded as a specific estrogen target tissue.

Alterations in estrogen levels during development affects the skeleton: use of an animal model, Environmental Health Perspectives, NCBI PubMed PMC1518867, 1995 Oct.

To investigate whether a short-term developmental exposure to estrogens can influence bone tissue, we have injected female mice with diethylstilbestrol (DES) from day 1 through day 5 of life. Additionally, a group of pregnant female mice were injected with different doses of DES from day 9 through 16 of pregnancy. Mice were then weaned at 21 days of age, and effects on bone tissue of the female mice were evaluated in adulthood (7-12 months of age).

These short-term treatments did not affect body weight of exposed mice. However, a dose-dependent increase in bone mass, both in the trabecular and compact compartments, was observed in the DES-exposed female offspring. Furthermore, femurs from DES-exposed females were shorter than femurs from controls. A normal skeletal mineralization accompanied these changes in the bone tissue. In fact, a parallel increase in total calcium content of the skeleton was found in concomitance with the increase in bone mass. Estrogen treatment induced an increase in the amount of mineralized skeleton when compared to untreated controls.

In summary, this report shows that alterations of estrogen levels during development can influence the early phases of bone tissue development inducing permanent changes in the skeleton. These changes appear to be related to bone cell programming in early phases of life.

Discussion

At the present time our result cannot either indicate or rule out any potential teratogenic or carcinogenic effect of the early exposure to DES in the skeleton of these female mice. It is interesting to know, however, that there have been a few self reports of spondylolisthesis in women exposed prenatally to DES (23). Thus, it may be clinically important to further investigate the possibility that exposure of the human population to exogenous estrogens could permanently affect skeletal tissue. In particular, it will be clinically relevent to evaluate whether low or high doses of these steroids could affect the skeleton in different manner, for instance increasing peak bone density or inducing skeletal malformations at higher doses. In conclusion, our results show for the first time that developmental exposure to estrogens during certain stages can permanently influence bone tissue in an animal model. The observed changes appear to be due to an effect on bone cell programming since differences in bone cell number and activity are retained through adulthood.

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