Stimulate

Inhibit

Maintains corpus luteum

Midcycle surge leads to ovulation

Na and water retention

Increase in clotting factors

Lipid alteration (decreased LDL, increased HDL, decreased cholesterol)

Estrogen is dominant in making the reproductive tract optimized for ______

Progesterone for _______

E: Fertilization (growth, development and maintenance of primary (fertility) and secondary (female form) sex characteristics, proliferation of endometrium, increased uterine and tubal motility, watery cervical secretions, suppression of FSH)

P: Implantation and maintenance of pregnancy (secretory endometrium, viscous low volume cervical secretions, decreased uterine motility (quieting effect), thermogenic effect (1 degree), suppression of LH release)

Follicular

(side note, seriously missed a period one time for 3 months without a pregnancy)

Progesterone

When temp rises for a few days you can get pregnant. 

Follicular

Pregnancy

I'm glad you asked, ok I may be getting a little cooky over here but today is 7 weeks until boards so go with it. 

Anyways, estrogen can be made in a variety of ways. It can be directly secreted by the ovary (E1). In men and postmenopausal women estrogen is not made this way. Andronstenedione is released from the adrenal glands and the ovarian stroma where fat, skin, mm, endometrium etc. carry aromatase and convert it to estrogen (E2)

GnRH dosing route (why)

FSH, LH, hCG dosing:

Estrogens, Progestins, analogues

Nasally (destroyed by gut)

Parenteral 

Orally (lipophilic, but has first pass metabolism). These are very highly protein bound (estrogen to SHBG with high affinity and low capacity, or albumin with low affinity and high capacity), (progesterone with CBG with high affinity/low capacity or with albumin high capacity/low affinity) 

Phase I oxidation and II conjugation with glucuronate and sulfate

Excretion via urine and feces

Estradiol

Esters of estradiol

Estrone

Conjugated estrogens

17-ethinylation (spot where liver likes to attack)

Examples: Mestranol, and 17-ethinylestradiol

Phyoestrogen (from soy)

Environmental (DDT, phenolic resins)

Endocrine disruptors

Act as weak estrogens, anti-estrogens, androgens, anti-androgens

Interference in reproduction and useful as postmenopausal nutritional supplement

Interfere with GnRH release

Inhibit synthesis (aromatase inhibitors)

Block estrogen receptor

Estrogen receptor antagonists

Clomiphene: useful for anovulatory infertility tx

Tamoxifen: useful in management of estrogen dependent cancer. Aromatase inhibitors are now used.

Selective estrogen receptor modulator

Useful for maintaining bone mass post-menopausally without extreme stimulation of breast or uterine tissue

Increases

Decreases

RU-486

Progesterone Receptor Antagonist

Useful as abortifacient with prostaglandin

Also for tx of Cushing's, glaucoma

Reverses uterine quieting effect --> uterine activity

Anti gonadotropin derived from androgens that exerts negative feedback on the pituitary without estrogenic effects

Commonly used for endometriosis

May cause virulization

GnRH analgotues

Decrease pituitary secretions at constant levels

Increase secretions at pulsatile admin

Used to tx endometriosis and prostatic cancer

Hormone responsive tumors

Endometriosis

Dysmenorrhea

Contraception

Hirsustism (if adrenal cause use GCC if ovarian use OCP)

Supression of postpartum lactation

Post menopausal osteoporosis

Menopause (paresthesias, mm cramps, arthralgia, anxiety, dizziness

Dysfunctional uterine bleeding

Contraception

Threatened or habitual abortion (luteal phase defect). May cause possible virulization of female fetus.

Differential Diagnosis of Amenorrhea

What is it and how to tx if progesterone admin causes uterine bleeding

Suggests that uterus is working (endometrium capable of response, presence of endogenous estrogen activity, ovarian activity, gonadodrophic stimulation, GNRH activity).

This is probably due to feed back mechanism failure

Patients should respond to Clominphene (ER antagonist), LHRH, HMG/hCG

What is and how to treat

Amenorrhea. Progesterone administration causes no uterine bleeding. Second progesterone admin with estrogen causes uterine bleeding. Gonadotropin estimation is low.

Either Group 1 hypothalamic failure (responds to GnRH secretion) Tx with GnRH or HMG/hCG

Group 1 pituitary failure (does not respond to stimulation by GnRH). Treat with HMG/hCG

What is and how to treat

Amenorrhea. Progesterone admin causes no uterine bleeding. Second admin with estrogen as well causes uterine bleeding. Gonadotropin estimation is high.

Ovarian insufficiency (genetic, acquired or iatrogenic)

Amenorrhea, Progesterone admin causes no uterine bleeding. Readmin with estrogen causes no uterine bleeding

What are the possible dx

Pregnancy

Traumatic amenorrhea

Congenital

oral contraception or parenterally

long acting injection

High, intermediate and low estrogen levels

Days 5-25, some with Fe for off days

mono, bi, and tri

Morning after pill

Alters tubal and uterine motility to interfere with implantation not with ovulation

Inhibit ovulation but not sufficiently. Effects on endometrial lining, uterine motility, and cervical secretions contribute to efficacy.

Decrease tubal, uterine motility and increase viscosity

May have spotting 

semisynthetic estrogen and 19-nortestosterone

Low constant doses for days 5-25

Inhibit GnRH release thus no ovum matures or is released. E: inhibits ovulation P: ensures menses

Increased clotting factors (VII, VIII, IX, X) (decreased PT/aPTT)

Lipid alterations (increased HDL and decreased LDL)

Increased TBG and total T4 (free T4 is normal)

Decrease

Phenobarbital, phenytoin

CV: thrombophlebitis, thromboembolism, platelet aggregation, 2.5 * risk of MI, 2-20 * risk of stroke, greatly compounded by >35 years, obesity, HTN, family hx, SMOKING

Impaired glucose intolerance

HTN (mild/fluid retention/responsive to diuretics)

Increased incidence of hepatoma

Increased incidence of gall bladder disease

Migraine

HTN

DM

epilepsy

Feedback: clomphine

Pituitary hypofunction: FSH/LH