APPENDIX VI : RECOMMENDATIONS FROM
THE 1992 DES WORKSHOP

I. Epidemiologic studies

A. Support registries of DES-exposed individuals as a resource for epidemiologic research.

1. Support follow-up of identified cohorts of DES-exposed individuals and controls.

2. Encourage collaboration between existing registries for key analyses where larger sample size is required for statistical power.

3. Increase numbers of registered individuals by:

(a) Linking mothers and offspring to existing DES registries and recruiting unregistered members of mother-child pairs identified through these registries.

(b) Registering newly identified individuals with a history of DES exposure.

B. Use DES registries as a resource to:

1. Define the risk of ovarian, breast, uterine, and cervical cancer in DES daughters and the risk of testicular and prostate cancer in DES sons.

2. Define the role of hormonal exposure in later life (i.e., oral contraceptives, tamoxifen, replacement estrogens, drugs that induce ovulation) in modifying cancer risks.

3. Assess the effects of DES on fertility, reproduction, and gonadal senescence.

4. Assess the association between in utero DES exposure on immune-mediated disease and psycho sexual development.

5. Assess the effects of DES on infants born to DES sons and daughters.

II. Basic science research

A. Develop a mechanism to identify and make available human tissue specimens, serum, and leukocytes from DES-exposed individuals for basic research.

B. Develop transplant-derived cell lines from patients with DES-induced clear cell adenocarcinoma (CCAC) of the vagina to permit in vitro testing of steroid receptors and drug sensitivity.

C. Further develop in vitro methods and animal models to screen for adverse effects following prenatal exposure to DES and other environmental endocrine disruptive compounds.

Basic research efforts should include:

1. Definition of molecular markers in DES-induced vaginal CCAC and precancerous lesions.

2. Definition of the role of co-factors in the development of cervical dysplasia in DES daughters.

3. Assessment of the influence of in utero DES exposure on the developing immune, musculoskeletal, endocrine, and central nervous systems

4. Elucidation of factors regulating normal mesenchymal/epithelial interactions in the developing genital tract and of how these are affected by DES exposure.

5. Study of primitive and classical hormone receptors.

6. Study of derivatives of Müllerian epithelium in males exposed to DES in utero.

7. Study of the genotoxic effect of estrogen on paramesonephric epithelium in the developing reproductive tract.

III. Studies of vaginal clear cell cancer

A. Support registry efforts for follow-up of vaginal clear cell cancer patients.

B. Review recent data from the Society of Gynecologic Oncologists survey and the American College of Surgeons tumor registry database on vaginal clear cell cancer.

C. Use registry data to define:

1. The age-incidence curve, survival rate, and recurrence rate of vaginal clear cell cancer and the incidence of second primary cancers (vaginal clear cell and other cancers).

2. The effect of exogenous hormones and pregnancy on the incidence, survival, and recurrence of vaginal clear cell cancer.

D. Develop a consensus for the primary treatment of women with stage I/II vaginal clear cell

cancer aimed at organ preservation and morbidity reduction.

E. Conduct Phase II clinical trials to define the role of new agents such as taxol in the treatment of patients with stage III/IV and recurrent vaginal clear cell cancer.

F. Assess the impact of cancer and cancer treatment on survivors of vaginal clear cell cancer, including coping mechanisms, body image, sexuality, child bearing, the development of intimacy, and mother-daughter relationships.

IV. Clinical studies of pregnancy outcomes in DES daughters

A. Conduct clinical studies to identify risk factors for premature delivery in DES daughters.

B. Define the role of tocolytic agents and cerclage in prevention of premature delivery.

V. Education and outreach efforts

A. Develop comprehensive educational programs for health providers and the general public concerning adverse health effects associated with DES exposure.

B. Disseminate recommendations for cancer screening and obstetrical care to health professionals and the DES exposed.

VI. Other

A. Coordinate efforts to support DES research at the NIH and to track the implementation of recommendations made at the 1992 DES Workshop.

B. Hold additional DES Workshops to discuss and disseminate new research findings.