Reproductive Pharm

Question 1

Which follicle discharges an immature ovum?

Answer 1

Graafian

Question 2

What is the time frame of menses? Preovulation phase? Ovulation? Postovulation phase?

Answer 2

Approximately: Days 1 to 3, Days 4 to 14, Day 14, and Days 15 to 28

Question 3

When does estrogen peak? Progesterone? FSH? LH?

Answer 3

Estrogen: Days 11-13.Progesterone: Days 20 to 24.LH: Day 13.FSH: Small peaks at days 4 and 13

Question 4

Describe the feedback loops between the gonadotropins and estrogen.

Answer 4

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.

Question 5

What secretes progesterone?

Answer 5

The corpus luteum (and in pregnancy, the placenta).

Question 6

What are the natural estrogens? The synthetic estrogens? Which are steroidal and which are non-steroidal?

Answer 6

Natural: estradiol, estrone, and estriol. Synthetic steroidal: ethinyl estradiol, mestranol, quinestrol. Synthetic non-steroidal: diethylstilbestrol, chlorotrianisene, and methallenestril.

Question 7

Where are the natural estrogens made and which is the most potent?

Answer 7

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.

Question 8

What conversions does aromatase perform?

Answer 8

Testosterone to estradiol and androstenedione to estrone.

Question 9

Which are more commonly used, steroidal or non-steroidal synthetic estrogens?

Answer 9

Steroidal. The non-steroidal diethylstilbestrol was reported to increase the risk of clear cell adenocarcinoma of the vagina and cervix.

Question 10

How do estrogens alter cellular function?

Answer 10

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.

Question 11

How is exogenous estrogen absorbed by the body? How is estrogen transported in the blood?

Answer 11

Easily absorbed through skin, mucous membranes, and the GI tract. Travels bound to sex hormone binding globulin or albumin.

Question 12

Describe the metabolism of estrogens.

Answer 12

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.

Question 13

What are the normal physiologic effects of estrogens?

Answer 13

They promote development of secondary sexual characteristics, stimulate growth of the follicles, endometrium, breast cells, and promote progesterone receptor synthesis.

Question 14

What are the cardiovascular effects of estrogens? Effects on bone? Body fat?

Answer 14

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.

Question 15

What are the main therapeutic uses of estrogens?

Answer 15

Contraception, treatment of primary hypogonadism, and as hormone replacement therapy after menopause.

Question 16

What are the side effects of estrogens? The contraindications?

Answer 16

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.

Question 17

What is tamoxifen? What is it used for? What are its side effects?

Answer 17

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.

Question 18

How does tamoxifen work?

Answer 18

Its anti-estrogen activity comes from blocking the association of estrogen bound receptors with coactivators in the nucleus.

Question 19

What is clomiphene citrate? What is it used for? What are its side effects?

Answer 19

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.

Question 20

Where do males synthesize progesterone?

Answer 20

In the testes and in the adrenal cortex.

Question 21

What stimulates progesterone production?

Answer 21

LH

Question 22

What is meant by “progestin”?

Answer 22

Synthetic progesterone.

Question 23

What are the normal physiologic effects of progesterone?

Answer 23

Stimulates endometrial development of glands, suppress growth of endometrium, trigger negative feedback on GnRH, FSH, and LH to suppress ovulation.

Question 24

What are progestins used for? What are the two different methods of administration?

Answer 24

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).

Question 25

What are the progestins and what are their side effects?

Answer 25

Medroxyprogesterone, norethindrone, norgestrel, and megestrol. Side effects: androgenic activity (hirsutism, acne), edema, bloating, anxiety, irritability, depression, muscular pain, increased risk of DVT.

Question 26

Does natural progesterone have more or less side effects than synthetic progestins?

Answer 26

Less. Fatigue and drowsiness are the common side effects of natural progesterone.

Question 27

When is progesterone/progestin contraindicated?

Answer 27

Thromboembolic disorders, liver disease (site of metabolism), undiagnosed vaginal bleeding, pregnancy.

Question 28

What are the three different types of pharmacologic contraceptives? Which is most effective?

Answer 28

Estrogen-progestin combination, progestin-only, and postcoital. The combination pill is most effective at 99.9% (when taken appropriately).

Question 29

What are the estrogen and progesterone effects in the combination pill?

Answer 29

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.

Question 30

Why would you use progestin-only pills? How is their administration different? What are the side effects of this pill?

Answer 30

Used when estrogen is contraindicated (such as breast or endometrial cancer, breast-feeding, pregnant, etc. See other slide for full contraindications of estrogen therapy). Taken every day during the month (no break period). More likely to produce irregular menstrual cycle and spotting. This pill is less effective than the combination pill.

Question 31

What is the postcoital pill? How does it work? When is it taken?

Answer 31

Levonorgestrel. Interferes with implantation or delays ovulation. Taken within 72 hours of unprotected intercourse.

Question 32

What is RU-486? What is it used for? How is it used?

Answer 32

It is a progestin antagonist that blocks the receptor. Stimulates uterine breakdown with subsequent abortion. Must be taken before day 49 of pregnancy and must be given in a hospital in case of an incomplete abortion with need of surgical assistance.

Question 33

What are the drugs used for erectile dysfunction? Which is the longest acting? How do they work?

Answer 33

Sildenafil citrate, vardenafil HCL, and tadalafil. Tadalafil is the longest acting. They are all phosphodiesterase 5 antagonists which increase cGMP to promote smooth muscle relaxation through decreased calcium concentration. This allows for the ability to get an erection. It does not cause an erection.

Question 34

What are some common causes of erectile dysfunction?

Answer 34

Nerve damage, arterial damage, smooth muscle damage. Diabetes, vascular disease, kidney disease, multiple sclerosis, atherosclerosis, stress, anxiety, guilt, depression, smoking, alcohol.

Question 35

Where else is phosphodiesterase 5 found?

Answer 35

Platelets, vascular and visceral smooth muscle, skeletal muscle.

Question 36

What are the side effects of PDE5 inhibitors? Contraindications?

Answer 36

Headache, dizziness, flushing, vision change, upset stomach, stuffy or runny nose, urinary tract infection, diarrhea. May cause non-arteritic anterior ischemic optic neuropathy from sudden decreased blood flow to the optic nerve. May cause sudden unsafe drop in blood pressure if given with alpha blockers or nitrates.

Question 37

How are PDE5 inhibitors given?

Answer 37

Orally. Rapidly absorbed from the GI tract and reach peak plasma concentrations within 1 to 2 hours.