Unit 1 - Pharmacology of Reproduction Flashcards Preview

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Flashcards in Unit 1 - Pharmacology of Reproduction Deck (30):

early follicular phase happenings

days 1-7
-menstruation occurs at the beginning of the follicular phase
-FSH and LH levels are increased relative to baseline
-estrogen and progesterone levels are low


late follicular phase happenings

days 7-14
-growth, maturation of ovarian follicles, and one follicle becomes dominant in growth and hormone escretion
-FSH levels decrease due to negative feedback
-estrogen levels increase due to positive feedback
-progesterone levels remain low
-endometrial lining continues to grow and thicken


pre-ovulation and ovulation happenings

days 13-14
-LH surge stimulates follicular rupture and ovulation occurs within 48 hours


luteal phase happenings

ruptured follicle develops into corpus luteum that makes large amounts of progesterone and estrogen
-progesterone facilitates thickening of endometrial lining and development of blood vessels
-absence of fertilization, the corpus luteum begins to degenerate and ceases hormone production
-thus levels of estrogen and progesterone drop, and menstruation occurs


what are the different levels of estrogens?

1. natural estrogens (E1/2/3)
2. synthetic estrogens
-steroidal synthetic estrogens
-nonsteroidal synthetic estrogens

all differ by their R2/3 side chains (C3/17)


what is the primary source of estradiol in premenopausal women?

-granulosa cells of ovarian follicles make estrogens
-estradiol can be converted to estrone and estriol in liver
-estrogens converted from androstenedione and testosterone in ovaries or in other tissues


what are examples of synthetic steroidal estrogens in use?

1. estradiol esters - estradiol valerate, estradiol cypionate
2. conjugated estrogens - estrone sulfate, equilin sulfate
3. aklyl estrogens - ethinyl estradiol, mestranol


what is the major circulating estrogen in premenopausal women, men, and postmenopausal women?

pre: estradiol
men/post: estrone


where is aromatase expressed?

estrogen-producing cells of ovaries, placenta, adrenal gland, adipose tissue, testicles, and brain


what are examples of nonsteroidal synthetic estrogens?

1. diethylstilbestrol (DES) was reported to increase risk of clear cell adenocarcinoma in vagina and cervix
2. chlorotrianisene
3. methallenestril


pharmocokinetics of estrogens

absorbed through skin, mucous membranes, and GIT
-in circulation, bind to SHBG (sex-hormone binding globulin), and albumin with lower affinity


pharmacokinetics of E2

mainly metabolized in liver to E1
-significant amounts of estrogens and active metabolites are excreted in bile and reabsorbed from intestine
-estradiol is not used orally frequently due to extensive first pass effect
--micronization increases t 1/2 of E2 and reduces GIT destruction
-excretion of inactive metabolites occurs via urine


effects of estrogen on female maturation and reproductive system

develpoment of secondary sexual characteristics and sexual organs
-stimulates proliferation of endometrium and follicular growth
-stimulates breast cell growth
-induces synthesis of progesterone receptors


negative feedback of estrogen

high estrogen causes negative feedback loop on anterior pituitary and hypothalamus to slow release of FSH and estrogen


positive feedback of estrogen

high concentrations at end of follicular phase to positively regulate pituiary to trigger FSH and LH release that causes ovary to produce more estrogen
-high estrogen and LH cause ovulation


cardiovascular effects of estrogen

"estrogen-alone" hormone therapy has no effect on CHD, but increases the risk of stroke and deep vein thrombosis in postmenopausal women


effects of estrogen on lipoprotein

increase HDL and decrease LDL levels


how is estrogen used as contraception

synthetic estrogen like ethinyl estrodiol (steroidal alkyl estrogen) is used with progestin to prevent pregnancy


postmenopausal hormone therapy?

give estrogen to reduce postmenopause symptoms like hot flashes, atrophic vaginitis, and osteoporosis


what are common adverse effects of estrogen therapy?

nausea, breast tension/pain, vaginal bleeding, headache, weight gain, HTN


relationship between estrogen therapy and breast/cervical/endometrial cancers

breast: controversial; previous showed increased risk with >5 year use, but recently no increase with estrogen alone
cervical: may increase
endometrial: may increase


relationship between estrogen therapy and HA, stroke, GB disease

increases risk of all


contraindications of estrogen therapy

strongly contraindicated if breast/endometrial cancer, endometriosis, and undiagnosed vaginal bleeding
-generally contraindicated if pregnant, thromboembolic disease, HTN, hepatic disease, or family history of breast/uterine cancer


what are antiestrogen therapeutics and example?

compounds that are estrogen receptor competitive antagonists (or partial agonists in some setting)
-include tamoxifen citrate and clomiphene citrate


affinity of tamoxifen for ER?

estrogen has much higher binding affinity for its receptor than Tamoxifen
-must be used in concentration much higher than estrogen to maintain inhibition of breast cancer cells
-given orally, 10-20 mg 2x daily, with 7-14 hour halflife


clomiphene citrate isomers

cis: zuclomiphene (weak estrogen agonist)
trans: enclomiphene (potent antagonist)


where is progesterone made?

secreted in females by CL of ovary
-in pregnancy, high levels are made and secreted by placenta
males make it in the testes
-adrenal cortex makes it in both sexes
-production is stimulated by LH and gonadotropin


physiological functions of progesterone

stimulates endometrium to develop secretory glands and support fertilized egg implantation
-low levels in first several weeks lead to miscarriage
-can suppress endometrial cancers b/c long-term use atrophies emdometrium
-high levels trigger negative FB on hypothalamus to stop releasing gonadotropin and suppress ovulation


what are the 2 general uses of progestins?

1. contraception - used in combo with estrogens or in progestin-only methods
2. hormone replacement therapy - postmenopausal women
-counters endometrial stimulatory effects of estrogen and reduces risk of endometrial cancer


what are the two types of progestins?

1. natural (micronized and transvaginal)
2. synthetic