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
oral rapidly inactivated
progesterone
HydroxySynthetic
progesterone
progesterone
Medroxy"
HRT, POP (Depro-provera)
no androgenicity
progesterone
Norethindrone
"
POP, COC
minimal androgenicity
2nd most potent Syn
Levonorgestrel
"
POP (Norplant), COC
dec HDL, inc LDL, exacerbates
most potent Syn
glucose tol, androgenicity
Norgestimate
"
POP, COC
inc HDL, minimal androgenicity
4th most potent Syn
Desogestrel
"
POP, COC
3rd most potent Syn
inc HDL, dec LDL, improved
glucose tolerance, minimal
androgenicity
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