VIBS 422 Lecture 12

What is DES?

synthetic non-steroidal estrogen (EDC)

When was DES first syntehsized?

1938

What was DES orignally used for?

prescribed to pregnant women to prevent miscarriage (ineffective)

Why was DES widely used?

• not patented

  • produced by 200+ companies

What type of EDC is DES?

estrogen mimic (strong ER agonist)

DES is classified as what 3 major toxic agents?

• carcinogen (cancer)

• teratogen (birth defects)

• mutagen (DNA mutations)

What receptor does DES activate?

estrogen receptor a (ERa)

How does DES biding compare to estrdiol?

similar affinity —> strong estrogenic effects

Is DES lipid soluble?

yes —> easily absorbed & stored

peak concentration of DES in body?

20-40 minutes

Half-life of DES?

Primary: 3-6 hours

Terminal: 2-3 days (enterohepatic recirculation)

What are DES metabolites?

Inactive: B-di-enestrol

Active: DES-epoxide, quinone metabolites

When was DES approved?

1941

When was DES widely used?

1941-1970

How many women were exposed in the US?

5-10 million

When was DES linked to cancer?

1971 (vaginal cancer)

Who are DES daughters?

females exposed to DES in utero

most important cancer risk in DES daughters?

clear cell adenocarcinoma (CCA) of vagina/cervix

Risk of CCA in DES daughters?

1 in 1,000

40x higher risk

Structural abnormalities in DES daughters?

• T-shaped uterus

• hooded cervix

• pseudopolyps

• cervical abnormalities

Reproductive complications in DES daughters?

• infertility

• ectopic pregnancy

• preterm delivery

Miscarriage statistic in DES daughters?

about 20% in first pregnancy

Infertility rate in DES daughters

about 28%

Cause of infertility in DES daughters?

uterine structural abnormalities

Additional health effects in DES daughters?

• breast cancer risk

• autoimmune disorders

• immune dysfunction

Nnn-reproductive effects of DES exposure

• weak immune system

• depression/anxiety

• arthritis

• cognitive impairment

Who are DES sons?

males exposed to DES in utero

Main effects in DES sons?

• epididymal cysts

• undescended testes

• small testes

Cancer risk in DES sons?

increased risk of testicular cancer

Fertility effects in DES sons?

sperm abnormalities & infertility

Why is DES considered multigenerational?

causes epigenetic changes passed to future generations

Effects in DES granddaughters?

• infertility

• ovarian cancer risk

Effects in DES grandsons?

• hypospadias (urethral defect)

• 20x increased risk

Why does DES cause reproductive abnormalities?

estrogen overstimulation during development —> altered organ function

Why are fetal exposures especially dangerous?

critical developmental windows —> permanent structural changes

Non-pregnancy uses of DES?

• menopause treatment

• prostate cancer

• acne

• contraceptive

• livestock growth enhancer

Special screening for DES daughters?

• 4-quadrant pap smear

• pelvic exam

• colonoscopy + biopsy

Why is regular screening critical?

CCA is slow-growing but difficult to treat