Flashcards in Reproductive Pharm Deck (37)
Which follicle discharges an immature ovum?
What is the time frame of menses? Preovulation phase? Ovulation? Postovulation phase?
Approximately: Days 1 to 3, Days 4 to 14, Day 14, and Days 15 to 28
When does estrogen peak? Progesterone? FSH? LH?
Estrogen: Days 11-13.Progesterone: Days 20 to 24.LH: Day 13.FSH: Small peaks at days 4 and 13
Describe the feedback loops between the gonadotropins and estrogen.
High estrogen and progesterone inhibit GnRH, FSH, and LH secretion. In the late phase, there is positive feedback with increased estrogen and an LH surge.
What secretes progesterone?
The corpus luteum (and in pregnancy, the placenta).
What are the natural estrogens? The synthetic estrogens? Which are steroidal and which are non-steroidal?
Natural: estradiol, estrone, and estriol. Synthetic steroidal: ethinyl estradiol, mestranol, quinestrol. Synthetic non-steroidal: diethylstilbestrol, chlorotrianisene, and methallenestril.
Where are the natural estrogens made and which is the most potent?
Estradiol comes from the granulosa cells of the ovary. Estrone and estriol are either converted from estradiol in the liver, or coverted from androstenedione and testosterone in adipose, bone, brain, or ovarian tissue via aromatase. The placenta also makes estriol. Estradiol is the most potent.
What conversions does aromatase perform?
Testosterone to estradiol and androstenedione to estrone.
Which are more commonly used, steroidal or non-steroidal synthetic estrogens?
Steroidal. The non-steroidal diethylstilbestrol was reported to increase the risk of clear cell adenocarcinoma of the vagina and cervix.
How do estrogens alter cellular function?
They bind cytoplasmic estrogen receptors, which then lose their heat shock proteins, translocate to the nucleus, homodimerize, and bind estrogen responsive elements to alter gene transcription.
How is exogenous estrogen absorbed by the body? How is estrogen transported in the blood?
Easily absorbed through skin, mucous membranes, and the GI tract. Travels bound to sex hormone binding globulin or albumin.
Describe the metabolism of estrogens.
Estradiol is metabolized to estrone in the liver. Estrogens undergo recycling with bile in the intestines. Estradiol is not given orally due to a significant first pass metabolism in the liver. Inactive metabolites are secreted in the urine.
What are the normal physiologic effects of estrogens?
They promote development of secondary sexual characteristics, stimulate growth of the follicles, endometrium, breast cells, and promote progesterone receptor synthesis.
What are the cardiovascular effects of estrogens? Effects on bone? Body fat?
May have ability to decrease risk of coronary heart disease (increased HDL, decreased LDL), and definitely increase the risk of stroke, DVT, and thrombosis in general. Decrease bone resorption. Increased body fat.
What are the main therapeutic uses of estrogens?
Contraception, treatment of primary hypogonadism, and as hormone replacement therapy after menopause.
What are the side effects of estrogens? The contraindications?
Nausea, breast pain, vaginal bleeding, headache, weight gain, hypertension, increased risk of breast cancer, endometrial cancer, DVT, pulmonary embolism, gallbladder disease, stroke, and heart attack. Strongly contraindicated in breast or endometrial cancer, endometriosis, or undiagnosed vaginal bleeding. Generally contraindicated in pregnancy, thromboembolic disease, hypertension, hepatic disease, or family history of breast or uterine cancer.
What is tamoxifen? What is it used for? What are its side effects?
A nonsteroidal anti-estrogen agent that blocks estrogen effects on mammary epithelium, but promotes estrogenic effects in endometrial and bone tissue. It is used to treat estrogen receptor positive breast cancer. Side effects include increased risk of endometrial carcinoma.
How does tamoxifen work?
Its anti-estrogen activity comes from blocking the association of estrogen bound receptors with coactivators in the nucleus.
What is clomiphene citrate? What is it used for? What are its side effects?
A nonsteroidal anti-estrogen agent that blocks estrogen receptors in the hypothalamus, interrupting the negative feedback loop. This causes enhanced GnRH secretion with increased FSH and LH to promote fertility. The cis-isomer is less abundant and is an estrogen receptor agonist. The trans isomer is more abundant and is anti-estrogen. Side effects include menopause symptoms, stomach pain, headache, GI distress, vomiting, and multiple pregnancy.
Where do males synthesize progesterone?
In the testes and in the adrenal cortex.
What stimulates progesterone production?
What is meant by "progestin"?
What are the normal physiologic effects of progesterone?
Stimulates endometrial development of glands, suppress growth of endometrium, trigger negative feedback on GnRH, FSH, and LH to suppress ovulation.
What are progestins used for? What are the two different methods of administration?
Contraception and hormone replacement therapy with estrogen to inhibit endometrial cancer risk. The two forms are micronized progesterone given orally (micronization decreases first pass effect), and transvaginal gel (avoid first pass metabolism and has fewer systemic side effects).
What are the progestins and what are their side effects?
Medroxyprogesterone, norethindrone, norgestrel, and megestrol. Side effects: androgenic activity (hirsutism, acne), edema, bloating, anxiety, irritability, depression, muscular pain, increased risk of DVT.
Does natural progesterone have more or less side effects than synthetic progestins?
Less. Fatigue and drowsiness are the common side effects of natural progesterone.
When is progesterone/progestin contraindicated?
Thromboembolic disorders, liver disease (site of metabolism), undiagnosed vaginal bleeding, pregnancy.
What are the three different types of pharmacologic contraceptives? Which is most effective?
Estrogen-progestin combination, progestin-only, and postcoital. The combination pill is most effective at 99.9% (when taken appropriately).
What are the estrogen and progesterone effects in the combination pill?
Estrogen: suppresses FSH to prevent maturation, suppresses LH to prevent ovulation. Progestin: suppresses LH to prevent ovulation, thickens cervical mucous to block sperm, and cause endometrial atrophy to decrease likelihood of implantation.