Episode 75 - Progesterone vs. Progestins

What is Progesterone?

  • Steroid hormone naturally produced in the body.
  • On the ‘WHO model list of Essential Medicines’ – it is considered essential
  • Actions: some are direct and some are through metabolites. This is why PO is better.
    • Modulates GABA
    • Induces CYP3A4
    • Prevents mineralocorticoid activity by binding to the MR stronger than aldosterone and glucocorticoids
      • Elevated progesterone reduces Na retaining effects of aldosterone. P withdrawl causes Na retention
    • Effects are amplified in presence of estrogens. Estrogen upregulates the PR.
    • Converts the endometrium to secretory stage to prepare the uterus for implantation. Makes the vaginal and cervical mucus thick and impenetrable to sperm.
    • Mitigates the trophic effects of estrogen.
    • Normal estrogen bleeding is progesterone-withdrawl
    • Decreases smooth muscle contractility of the uterus
    • Importantly involved in sex-drive in females
    • No link to breast CA (unlike progestins – see below). In fact, RR of estrogen with progesterone was 1.00 but 1.69 for estrogen with other progestins. http://link.springer.com/article/10.1007%2Fs10549-007-9523-x
    • Research into possible benefit in TBI
    • Effects on Serotonin receptors. This provides an explanation for why some people resort to substances that enhanceserotonin activity such as nicotine, alcohol, and cannabis when their progesterone levels fall below optimal levels. P may be beneficial in addiction.
    • Other effects:
      • Decreased irritability
      • Suppress immunity during preganancy
      • Raises epidermal growth factor-1 (EGF-1)
      • Increases core temp during ovulation
      • Reduces spasm and relaxes SM
      • Acts as anti-inflammatory
      • Reduces GB activity
      • Normalizes blood clotting and vascular tone, zinc, and copper levels
      • Prevent endometrial cancer
      • Role in signaling insulin release and pancreatic function
    • Metabolites:
      • 5a-dihydroprogesterone & allopregnanolone helps modulate GABA (makes it calming)!
    • Progesterone is great for PMS – but have to use high doses
    • P synergistic with E2 (as opposed to progestins)
      • Modulates effects of excess estrogen: fluid retention, headaches, bloating, bleeding, fibroids
    • ALL menopausal women NEED progesterone! Even if the don’t have a uterus!!
      • Protects against breast CA, CAD, and CVD
    • Side effects:
      • Breast/nipple soreness
      • Somnolence (oral only)

 

What are Progestins?

  • Synthetic chemical with progesterone-like activity
  • Actions:
  • Uses:
    • Hormonal contraception: OCPs, IUD
      • These were the first oral contraceptives, around 1950.
    • Antiandrogens: drospirenone, medrogestone, megestrol acetate, nomegestrol
  • Side effects:
    • Bloating, HA, fatigue, weight gain, depression, increased PMS Sxs (stimulates the E receptor), CAD, CVD, DVT, PE, dementia, CA, DM
    • Depression
    • Breast swelling/tenderness
    • Irregular bleeding
    • Weight gain
    • Fluid retention
    • Increased breast CA risk
    • Increased cardiovascular disease risk
    • Stimulates E receptor site
  • FDA considers progesterone = with MPA yet MPA is Cat X in pregnancy