Progesterones Progesterones and Breast Cancer and Breast Cancer Endogenous and Exogenous Endogenous and Exogenous Synthetic or Natural Bio-identical Synthetic or Natural Bio-identical Progestins, Progestogens or Progestins, Progestogens or Progestagens Progestagens “ “ Act like progesterone” Act like progesterone” Dr Ellen C G Grant Dr Ellen C G Grant MBChB, DObst RCOG [email protected]
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Progesterones and Breast Cancer Endogenous and Exogenous Synthetic or Natural Bio-identical Progestins, Progestogens or Progestagens “Act like progesterone”
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Progesterones Progesterones and Breast Cancerand Breast Cancer
Endogenous and Exogenous Endogenous and Exogenous
Synthetic or Natural Bio-identicalSynthetic or Natural Bio-identical
Progestins, Progestogens orProgestins, Progestogens or ProgestagensProgestagens
““Act like progesterone”Act like progesterone”
Dr Ellen C G GrantDr Ellen C G Grant MBChB, DObst RCOG
• 156 down regulated156 down regulated• Striking Regulation of Striking Regulation of Secretory Proteins Secretory Proteins • Water and Ion Channels Water and Ion Channels • Signalling MoleculesSignalling Molecules • Immune ModulatorsImmune Modulators
• Endometrial Development Endometrial Development • Embryonic Interactions.Embryonic Interactions.
P upregulated genesP upregulated genes
• cholesterolcholesterol trafficking and transport trafficking and transport • apolipoprotein E 100-foldapolipoprotein E 100-fold• prostaglandin (PG)prostaglandin (PG) biosynthesis (PLA2) and biosynthesis (PLA2) and
• Immune ModulatorsImmune Modulators (major histocompatibility (major histocompatibility complex class II subunits) and other cellular complex class II subunits) and other cellular functions functions
• Genes involved in water and ion Genes involved in water and ion transport - transport - K(+) ion channelK(+) ion channel
• Genes corresponding to IGFBP-1, glycodelin, Genes corresponding to IGFBP-1, glycodelin, CPE1-R, Dkk-1, mammaglobin, and ApoDCPE1-R, Dkk-1, mammaglobin, and ApoD.
↑↑↑↑ Cu/Zn ratios in sweatCu/Zn ratios in sweat (serum and hair) (serum and hair) in in treatedtreated women - parts per billion at Biolab women - parts per billion at Biolab
RCGP OCRCGP OC Study Study VascularVascular
• 1974 DVTHROMBOSIS /PE 5.66DVTHROMBOSIS /PE 5.66• Heart disease 5.2• Cerebrovascular 4.1 DeathsDeaths• 1981 VascularVascular 4.24.2• non smoker 1.6 - 4.6• smoker 3.4 - 7.4 • 1983 AMI +Toxaemia history 41.0• 1999 Cerebrovascular Cerebrovascular +10 years+10 years 2.72.7
RCGP OC Study - RCGP OC Study - CancersCancers
• Breast cancer age 25-29 2.53
• Breast cancer age 30-34 3.33• Breast + 10 yrs 10.17• Breast 8-9 yrs later 15.8• Breast cancerBreast cancer deaths deaths 154 5- 9 yrs later 1.51.5• Lung cancerLung cancer 75 1.3 + 10 yrs 1.61.6 • Liver cancer 5 5.0Liver cancer 5 5.0
Effects of P on developmentEffects of P on development• Most pregnancy Most pregnancy ProgesteroneProgesterone use use nownow• ↑↑ Cancers in children,Cancers in children, DES breast, vaginal DES breast, vaginal