Estrogens

SOURCE = ovary/placenta in pre-menop. women, adipose tissue (DHEA->Estrone) in men and post-menop. women

GENERALLYuterine and breast cell proliferation and growth, bind and Sex Binding Globulin (SBG), regulate P receptor expression, natural t1/2

< synthetic t1/2, excreted in bile and undergo enterohepatic circulation (EHC) until glucuronidated and excreted in urine,

EFFECTS involve female sex characteristics, control of menstruation and pregnancy, and include clotting factors (thrombosis), SBG,

HDL, Insulin receptors, Na retention, LDL, can ALSO cause N/V, cramping, fluid retention, dizziness/HA, breast discomfort

Aromatase (induced by FSH and LH) converts androstenedione and testosterone to estrone and 17B-estradiol respectively

Rate limiting step for E and P synthesis is conversion of cholesterol to pregnenolone

Estrogens have neg. feedback loop on pituitary (decrease LH) and hypothalamus (decrease GnRH), serotonin

Hormone / Class / Use / Toxicity / Miscellaneous
17B-Estradiol / Natural / most potent, present in placenta,
Estrone / " / metabolite of 17B-E, present in placenta
Estriol / " / metabolite of 17B-E
Equilin Sulfate / Conjugated / HRT / require met. activation
Estrone Sulfate / " / HRT / require met. activation
Ethinyl Estradiol / Synthetic / OC (most used), COC / Mestranol is inactive precursor
Mestranol / " / OC
Diethylstilbestrol / Non-steroidal / OC / cervical/vaginal cancer / used 40 years ago to prevent miscarriage
Tamoxifen / Anti-estrogen
Clomipine / "

Menopause symptoms include hot-flashes (NE mediated), osteoporosis (E prevent further bone loss), urogenital atrophy, sleep and mood disorders

HRT often include P to prevent effects of unopposed E (esp endometrial cancer)

Estrogens HDL and LDL (oral better than t/dermal), prevent osteoporosis (0.625 mg/day for conjugated or 0.005 mg/day synthetic)

Estrogen alone therapy only for P intolerance, hysterectomy, poor lipid profiles

HRT osteoporosis, cardiovascular disease (DON'T use in preexisting heart disease), stroke, and Alzheimers (cognitive decline)

BUT risk for breast cancer and ovarian cancer

REMEMBER HRT good preventative but poor intervention



Progestins

SOURCE = testes after LH stimulus and adrenals in men and post-menop. women

GENERALLY uterine and breast cell proliferation and growth (think of as brakes for estrogen), bind Corticosteroid Binding Globulin

(CBG), glucuronidated and excreted (no EHC)

EFFECTS involve mammary development, uterus implantation, body temp, endometrial sloughing (reduced P), pregnancy maintenance,

inhibition of uterine contraction, can ALSO cause spotting, weight gain, acne hirsutism

Progesterones interact with several types of receptors (androgen, glucocorticoid, and estrogen receptors) and all have risk of thrombosis

Hormone / Class / Use / Side Effects/Toxicity / Miscellaneous
Progesterone / Natural progesterone / oral rapidly inactivated
Hydroxy-progesterone / Synthetic progesterone
Medroxy-progesterone / " / HRT, POP (Depro-provera) / no androgenicity
Norethindrone / " / POP, COC / minimal androgenicity / 2nd most potent Syn
Levonorgestrel / " / POP (Norplant), COC / dec HDL, inc LDL, exacerbates glucose tol, androgenicity / most potent Syn
Norgestimate / " / POP, COC / inc HDL, minimal androgenicity / 4th most potent Syn
Desogestrel / " / POP, COC / inc HDL, dec LDL, improved glucose tolerance, minimal androgenicity / 3rd most potent Syn
RU-486 / Anti-progesterone / medical abortion

Menstrual Cycle = Follicular Phase where GnRH FSH and LH -> E -> E surge pos. feedback cause peak LH/FSH -> ovulation

Luteal Phase where E and P (corpus luteum) -> high [E+P] neg feedback on HPA to dec LH/FSH

Remember, beginning of luteal phase E but still high overall concentrations present

Oral Contraceptives prevent ovulation by inhibiting LH/FSH surge and release

Progesterone Only Pills associated with menstrual irregularities but Estrogen Dominant (2nd generation OC) Pills associated with endometrial cancer

(require 12 days of progesterone)

Ortho Tri-Cyclen (triphasic) most commonly prescribed COC (also reduce acne), Triphasil 2nd, Ortho-Novum 3rd

COCs inhibit ovulation (supp FSH/LH thus supp ovulation), thicken cervical mucosa, and alter endometrial lining to prevent implantation

BENEFITS include ovarian and endometrial cancer, fibroadenomas, fibrocystic breast disease, menstrual blood loss, acute PID, and

cycle regularity

SIDE EFFECTS include [thrombosis (esp SMOKERS), breast cancer (esp long term use), HTN, cervical dysplasia/cancer (esp HPV,

smoking), bile stasis, stroke and MI (esp older users)] for ESTROGEN and [reduced HDL:LDL ratio and impaired glucose tolerance]

for PROGESTERONE

CONTRAINDICATED in smokers > 35 years old, thrombotic disease, hormone sensitive tumors, pregnancy, stroke, MI, HTN (160/100+)

POP good for lactating patients, smokers, HTN but have increased rate of failure and menstrual disturbances