Reproduction Flashcards
What are the three estrogens produced by female body? Where? Which one is the major circulating estrogen in premenopausal? postmenopausal?
- Estradiol: Granulosa cells of ovary
- Estrone: converted from estradiol in liver
- Estriol: converted from estradiol in liver
Premenopausal- Estradiol
Postmenopausal- Estrone
What is the enzyme important for estrogen biosynthesis that converts testosterone to estradiol and androstenedione to estrone?
Aromatase
Of the synthetic estrogens, what are 2 estradiol esters? 2 conjugated estrogens? 2 alkyl estrogens?
Estradiol Esters: estradiol valerate, estradiol cypionate
Conjugated Estrogens: estrone sulfate, equilin sulfate
Alkyl Estrogens: ethinyl estradiol, mestranol
What are the pharmacokinetics of estrogen therapy? Which estrogen can NOT be given orally due to significant first pass metabolism?
- Absorbed through skin, mucus membranes, GI Tract;
- Body-wide distribution via sex-hormone binding globulin (SHBG)
- Estradiol is not used orally
What are the physiological effects of Estrogen?
- proliferation of endometrium and follicular growth
- breast cell growth
- induces synthesis of progesterone receptors
- decrease bone resorption
High estrogen levels normally have a negative feedback system except for at which time during menstruation cycle?
late follicular phase- positive feedback of estrogen and LH trigger ovulation
What are some adverse effects of estrogen therapy?
- increase body fat, salt/fluid retention –> HTN
- increase coagulation and risk of stroke
- may increase risk of breast, cervical, endometrial cancers
- Nausea, breast tension/pain, vaginal bleeding, headache
What are 3 therapeutic uses of estrogen therapy?
- Contraception (frequently combined with progesterone)
- Primary Hypogonadism (replacement therapy)
- Postmenopausal hormone therapy (reduce symptoms, prevent osteoporosis)
In what patients is estrogen therapy contraindicated?
- Strongly contraindicated in breast or endometrial cancers, endometriosis, undiagnosed vaginal bleeds;
- Relatively contradinicated in pregnancy, thromboembolic disease, HTN, hepatic disease, family history of breast or uterine cancer
What is Diethylstilbestrol?
(DES)
- Non-steroidal synthetic estrogen
- no longer used due to increased risk of clear cell adenocarcinoma of vagina & cervix
Where does Tamoxifen act and what effect does it have at these sites? What is it used to treat and how? Adverse effects?
- Anti-estrogenic on mammary epithelium; Pro-estrogenic on uterine endometrium & bone
- Used to treat ER+ breast cancers (competitive antagonist but need high levels to overcome estrogen affinity)
- prolonged use increases risk of endometrial carcinoma
What is the action and use of Clomiphene citrate? SEs?
- used to stimulate ovulation
- Blocks estrogen binding to hypothalamic receptors (no estradiol negative feedback on gonadotropins) –> increased secretion of gonadotropins & LH –> ovulation
- SE: Hot flashes, multiple pregnancy
Where is progesterone synthesized? What hormones stimulate its production?
- secreted by corpus luteum during ovulatory phase
- secreted by placenta during pregnancy
- adrenal cortex in both sexes
- males: testes
- -Production is stimulated by luteinizing hormone and gonadotropin
What are 3 physiological functions of progesterone?
- Stimulates endometrium to develop secretory glands, support egg implantation (low progesterone may lead to miscarriage)
- Long-term use has atrophic effect on endometrium (suppressing effect on endometrial cancers)
- High levels trigger (-)feedback to hypothalamus to stop gonadotropin release and suppress ovulation
What is the therapeutic use of Norethindrone and those in its class?
(synthetic progestin)
Use: Contraception (in combo with estrogens or on its own); Hormone replacement therapy (reduces risk endometrial cancer)
What are some adverse effects of Megestrol and those in its class?
(synthetic progestin- more SEs than natural progestins)
- edema
- abdominal bloating
- androgenic activity: can cause hirsutism & acne
- risk of DVT/PE
In what patients is Norgestrel and those in its class contraindicated?
Contraindicated in thromboembolic disorders or patients with such a history, liver disease (metabolized in the liver), undiagnosed vaginal bleeding, pregnancy (atrophy of endometrium leading to birth defects)
What are 4 synthetic progesterone agents?
Medroxyprogesterone
Norethindrone
Norgestrel
Megestrol
What are the 3 combination oral contraceptives? What is the mechanism of action of the estrogenic agent and the progestational agent?
Monophasic Ortho-Novum
Biphasic Ortho-Novum
Triphasic Ortho-Novum
Combinations of norethindrone with ethinyl estradiol
ESTROGEN: constant levels suppress FSH (follicle maturation) and LH surge
PROGESTERONE: suppress LH secretion (prevent ovulation), thicken cervical mucus (impenetrable to sperm), endometrial atrophy (unreceptive to implantation)
What are the advantages and disadvantages to the “mini pills”
(progesterone-only oral contraceptives)
- Advantage: if estrogens contraindicated (FH of endometrial cancer, if lactating (estrogen reduces milk production)
- Disadvantage: less effective than if in combination form, irregular menstrual cycle
What is Levonorgestrel? Mechanism of action?
(Plan B) / Postcoital contraceptive
- Must be taken within 72hrs of coitus
- most likely prevents implantation
What is Mifepristone? Use? Important information?
“abortion pill”
- Competitively binds to progesterone receptor (leading to detachment of fetus); glucocorticoid receptor antagonist (Cushing’s syndrome)
- Must take early in pregnancy (by day 49); oral administration; must be given by doctor in medical facility prepared for surgery if abortion incomplete
What are 3 agents that are 1st line treatment for erectile dysfunction? Mechanism of action? Which of the 3 is the longer-acting?
Sildenafil citrate (Viagra) - half life 4hrs Vardenafil HCl (Levitra) - half life 4hrs Tadalafil (Cialis) - half life 17.5hrs Bind catalytic site of PDE5; inhibits PDE5 breakdown of cGMP --> decreased Ca --> smooth muscle relaxation --> erection
What are some side effects/cautions of vardenafil and those in its class?
(PDE5 inhibitors)
- Headache, dizziness
- change in vision (NAION- sudden decrease blood flow to optic nerve)
- contraindicated if on nitrates or alpha-blockers (unsafe drop in bp)
- do NOT use more than once a day
