Term
| LH and FSH. Which is biphasic and which is uniphasic? |
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Definition
LH is Biphasic.
FSH is Uniphasic |
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Term
| What affect does prolactin have on GnRH secretion and what does that mean to us? |
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Definition
| Prolactin, via negative feedback, inhibits GnRH release. This gives a post-partum contraceptive effect. |
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Term
| What would happen in hyperprolactinemia? How could we treat it? |
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Definition
| May cause Amenorrhea, infertility. It would be treated with DA Agonist (bromocriptine) or by surgical removal of pituitary tumor. |
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Term
| What can produce negative feedback on FSH/LH? |
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Definition
*Inhibin: Produced in ovaries and testes and decreases Beta-Subunit expression
*Testosterone: Produced in Leydig cells, will feed back and inhibit GnRH.
*Progesterone: Will suppress GnRH and LH/FSH production at both levels of H/P axis. This is the basis of oral contraceptives. |
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Term
| What do LH, FSH, hCG, and TSH have in common? |
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Definition
| They all share the same Beta-Subunit. |
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Term
| What is the function of FSH in women? |
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Definition
| Stimulates the production of ovarian follicles, and the production of estrogen by those follicles |
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Term
| What is the function of LH in women? |
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Definition
| Simulates further development of ovarian follicles, triggers ovulation, and stimulates production of estrogens, progesterone, and relaxin by ovarian cells. |
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Term
| What is the function of Estrogens? |
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Definition
Controls the development/maintenance of the:
*Endometrial lining of uterus,
*Secondary sex characteristics
*Fluid and Electrolyte Balance
*Protein Anabolism
*CNS, bone, skin, |
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Term
| Will FSH primarily lead to estrogen or progesterone? |
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Definition
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Term
| Will LH primarily lead to estrogen or progesterone? |
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Definition
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Term
| What are the metabolic forms of estrogens? |
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Definition
| The natural form is 17-Beta-Estradiol. This is oxidized first to Estrone (1/3 activity) and then further oxidized to Estriol (1/16 activity) |
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Term
What is the function of Progesterone?
*On the endometrium
*On the mammary glands
*On GnRH and Prolactin |
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Definition
Is a hormone of maturation that works:
*With estrogens to prepare the endometrium for implantation
*With the mammary glands for milk secretion.
*High levels of progesterone will inhibit GnRH and Prolactin |
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Term
*What happens in menstruation when a fertilization and implantation does not occur (Phase I)
*How long does this last? |
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Definition
*A sudden reduction in the levels of estrogen and progesterone. The stratum functionalis portion of the endometrium sheds. This results in periodic discharge of 25-65 mL of blood, tissue fluid, epithelial cells, etc.
*This lasts an average of 5 days. |
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Term
| *What happens in the menstrual cycle after endometrial shedding has already occurred? |
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Definition
*This is the time between menstruation and ovulation lasting 6-13 days.
*FSH and LH stimulate the next ovarian follicle to produce more estrogens.
*The estrogens stimulates the repair/thickening of the endometrium. |
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Term
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Definition
| It is the rupture of the ovarian follicle to release the immature ovum. This occurs because estrpgen results in a surge of LH This usually occurs on day 14 in a 28 day cycle. |
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Term
| What are the Estrogen, LH, GNRH, and FSH levels during ovulation? |
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Definition
| Estrogen is high leading to an LH surge which is what causes ovulation. The high levels lead to inhibition of GnRH and FSH by feedback. |
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Term
What happens after ovulation?
How long does this last? |
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Definition
| This is the time (Days 15-28) between ovulation and the start of the next menstrual phase. LH stimulates the formation of the Corpus Luteum from the ruptured follicle. This secretes increased estrogens and progesterone. Then progesterone, the dominant hormone at this time, prepares the endometrium to receive a fertilized ovum. If fertilization does not occur, the rising levels or estrogen and progesterone inhibit GnRH and LH and therefore the Corpus Luteum degenerates. Then, once estrogen and progesterone are no longer being produced, the menstrual cycle starts again. |
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Term
| What affect will HMG-CoA Reductase Inhibitors (Statins) have on sex hormones? |
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Definition
| Statins work by preventing the formation of cholesterol, which is a precursor to the sex hormones. However, this effect is usually not enough to inhibit sex hormone production. |
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Term
| What does testosterone and androgens have to do with Estrogen synthesis? |
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Definition
| They are precursors to 17-Beta-Estradiol. |
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Term
| What changes in relative levels between the estrogens occurs at menopause? |
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Definition
| Before Menopause, there is usually more Estradiol than Estrone(1/3 activity). After Menopause there is usually more Estrone than Estradiol. |
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Term
What happens to estrogen production at menopause?
What about levels of GnRH, LH, FSH, and androgens? |
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Definition
*As the follicle supply is exhausted, estrogen is no longer being produced as much and atrophy of estrogen dependent tissues occurs.
*The levels of GnRH, LH, and FSH increase dramatically as there is no longer the negative feedback from estrogen and Androgen levels increase. |
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Term
| What kind of Receptor does Estrogen bind? |
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Definition
| Intracellular Steroid Receptors. Which activate HREs (Hormone Response Elements) to stimulate/inhibit DNA transcription. |
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Term
| What are the physiological effects of Estrogens? |
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Definition
*Promotes secondary sex characteristics: Hair growth, softening of skin, growth of breasts, fat in thighs, hips, and buttocks
*Increases cervical gland secretions
*Induces expression of progesterone and LH receptors |
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Term
| What are the possible long term effects of estrogen drug therapy? |
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Definition
*Prevent coronary atherosclerosis BEFORE menopause.
*Improved cognition in dementia
*Skeletal integrity and prevention of tooth loss.
*Protects against macular degeneration |
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Term
Metabolism/Elimination of Estrogen
*Interconversion of Estradiol/Estrone.
*Glucuronidation, Sulfination, Aromatic Hydroxylation |
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Definition
*Oxidation, Reduction:
Estradiol (Reduction/Oxidation) Estrone (Oxidation) Estriol
*Estradiol and Estriol can be glucuronidated and this can undergo recycling OR renally eliminated.
*Estrone can be sulfinated (then recycled OR renally eliminated), or Ar-hydroxylated (then renally eliminated). |
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Term
| What are the two main types of contraceptives? |
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Definition
*Progestin-only pill (POP)
*Combined pill. (Combination of an oestrogen with progesterone) |
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Term
Why is 17-Beta estradiol not useful as an oral contraceptive?
What is used instead? |
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Definition
*Because it is metabolically inactivated by First Pass.
*Ethinyl-estradiol is longer acting and has better affinity due to replacing the 17 position with an ethinyl moiety. Also used is Mestranol which is the methyl ether prodrug of ethinylestradiol(CYP oxidation converts to active form). |
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Term
| What is the mechanism of estrogen as a contraceptive? |
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Definition
| Works by putting negative feedback on the H/P axis and therefore FSH is not produced to stimulate follicular growth thus an ovulation cannot occur. |
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Term
What is the mechanism of progesterone as a contraceptive?
(Though progesterone is not used orally because of low bioavailability and short duration of action, rather a progestin is used) |
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Definition
*When used in combination with an estrogen, progestins inhibit the LH surge that is required for ovulation.
*Progestin only pills are thought to create a hostile cervical environment(thickening of the mucus), possibly cause endometrial atrophy which could inhibit implantation, and will decrease penetration of sperm and ovum transport. |
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Term
| What other receptors can progesterone bind? |
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Definition
| It can bind receptors for estrogen, and androgens and other which can lead to often undesired side-effects. |
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Term
| What are the first generation progestins? |
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Definition
| It can bind receptors for estrogen, and androgens and other which can lead to often undesired side-effects. |
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Term
| What are the first generation progestins? |
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Definition
*Norethindrones, Ethynodiol, Norgestrel,
*Derivatives of testosterone with structural changes (now called 19-Androstanes) that decrease androgenic activity while retaining progesterone activity and possibly estrogen activity. |
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Term
| What are the second generation progestins? |
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Definition
*Levonorgestrel
*The active isomer of Norgestrel, a first generation. It has the highest progesterone activity, but also has high androgenic activity. |
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Term
What are the third generation progestins?
(this is the important one**) |
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Definition
*Desogestrel(metabolite Etonorgestrel), Norgestimate(metabolite Norelgestromin), are derivatives of levonorgestrel
*Comparable to the second generation progestins, however with VERY LITTLE estrogenic activity and LOWER androgenic activity. |
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Term
| What are the fourth generation progestins? |
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Definition
*Drosperinone.
*A Spironolactone with progestational and anti-mineralcorticoid activity. Has NO androgenic, estrogenic, or glucocorticoid activity |
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Term
| How must a patient take oral contraceptives to be considered “appropriate use?” |
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Definition
| A dose may not be missed and the doses must be taken at the SAME TIME of day every day, otherwise efficacy drops to 95%. |
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Term
| How has dose changed from older formulations to newer ones? |
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Definition
Newer formulations have 1/5th the estrogen and 1/10th the progestin compared to older contraceptives.
*Doses of estrogen were reduced to 30-35mcg when it was found that there was increased risk of pulmonary embolism, MI, and stroke when over 50mcg. |
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Term
| What is a monophasic Oral Contraceptive? |
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Definition
| When a contraceptive contains an equal ratio of estradiol and progestin and this ratio does not change throughout the dosing. These are LEAST likely to cause side effects. |
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Term
| What is a Biphasic/Triphasic Oral Contraceptive? |
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Definition
| In these, the ratio of estradiol to progestin changes throughout dosing to better mimic natural hormone levels. A Triphasic changes dose every 7 days. All including monophasics will have a placebo phase to allow for the menstrual period. |
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Term
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Definition
| The oral form for giving estrogen since 17B-estradiol does not survive First Pass. Used in Oral Contraceptives. |
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Term
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Definition
| Contraceptive. Usually administered by IUD. |
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Term
| Drug – Medroxyprogesterone Acetate |
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Definition
| Contraceptive. Usually administered IM. An 17-ester and a 6-methyl is added to progesterone to decrease Reduction reactions. Gives prolonged, even oral activity. |
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Term
| Drug – Norethinidrone, Ethynodiol |
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Definition
| Contraceptive. 1st generation progestin |
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Term
| Drug – Norgestrel, Levonorgestrel |
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Definition
*Contraceptive. 1st generation progestin (Norgestrel) and
*Contraceptive 2nd generation (levonorgestrel); Active isomer
*Both have higher progesterone activity with low estrogenic, but also have high androgenic activity. |
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Term
| Drug – Desogestrel, Norgestimate |
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Definition
*Contraceptive. 3rd generation progestin.
*High progesterone, Very low Estrogenic, and lower androgenic activity. |
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Term
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Definition
*Contraceptive. 4th generation progestin.
*A Spironolactone derivative. Has progestational and anti-mineralcorticoid activity. NO effect on glucocorticoid, androgenic, or estrogenic. |
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Term
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Definition
A monophasic oral contraceptive. Uses Drosperinone(4th) as its progestin.
*Acts by preventing ovulation and makes it harder for sperm to reach the uterus.
*Due to weak K+ sparing diuretic effect, may be preferred by women who experience bloating(Water retention) and hirsutism. |
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Term
| Drug – POP (Progestin only pill) |
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Definition
*Oral Contraceptive. Works by thickening the cervical mucosa to stop sperm. Not strong enough of a dose to stop ovulation. Effect decreases after 22 hours. (Only 99.5% effective with perfect use compared to 99.9% *Useful for women who are intolerant to estrogen containing contraceptives.
*Greater degree of irregular bleeding. Other ADRs are headache, breast tenderness, nausea, and dizziness. |
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Term
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Definition
*A transdermal patch contraceptive
*Applied to buttock, abdomen, upper outer arm or upper torso in the first day of menstrual period. A new patch is applied every week for three weeks. Followed by a patch free week.
*If patch is partially or completely detached for less than one day, then it has to be replaced only if the adhesive is worn off. After a day it must be replaced. Backup contraception should be used until the new patch has been applied for 7 days. |
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Term
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Definition
*A copper containing IUD.
*Works by making sperm non-viable and by decreasing its chance to reach the ovum.
*Low side effects, though may cause endometritis, pelvic infection, allergy, tubal damage, and uterine perforation. |
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Term
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Definition
*A progesterone containing IUD.
*Inserted by physician and replaced every 12 months. Works primarily by activity on the cervix but can sometimes inhibit ovulation.
*Efficacy lower at 98%.
*ADRs: intermenstrual spotting, pelvic inflammatory disease |
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Term
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Definition
*A progestin (Levonorgestrel) containing IUD.
*Has been proven over 99% effective for the five years following insertion. |
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Term
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Definition
*A Vaginal Contraceptive ring containing ethinyl estradiol.
*Efficacy is 98-99%.
*Associated with a higher incidence of vaginitis, vaginal discomfort, and vaginal infections compared to IUDs.
*Inserted on the fifth day of cycle and is left in place for three weeks. |
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Term
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Definition
*An IM contraceptive containing medroxyprogesterone acetate.
*Injection is given every 12 weeks.
*Works by preventing ovulation and also causes changes to the cervical mucus and endometrium |
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Term
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Definition
*A SC contraceptive containing medroxyprogesterone acetate. Comes in a prefilled syringe. Administered every three months to anterior thigh or gluteus region.
*Efficacy is comparable to perfect use of oral contraceptives. |
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Term
| What are the side effects of too high estrogen dose in a contraceptive? |
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Definition
| Nausea, Vomiting, Bloating, decreased libido, and breast tenderness. |
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Term
| What are the side effects of too high Progesterone in a contraceptive? |
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Definition
| Actne, Hirsutism, and vaginal yeast infections. |
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Term
| *What are the Serious Adverse effects of contraceptives? |
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Definition
*Increased risks of breast cancer, cervical cancer, MI, stroke, Venous thromboembolism, DVT, pulmonary embolism.
*These risks are small and closely associated with health status and presence or CV risk factors, as well as the estrogen dose.
*Higher risk in smoking, obesity, family history of coronary artery disease, age>35, concomitant disease states.
*These serious adverse effects largely do not apply to progestin only products because they are not associated with CV complications. |
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Term
| How should a patient be advised on the serious symptoms of contraceptives? |
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Definition
Acronym ACHES: Abdominal pain, Chest pain, Headache, Eye pain, and Severe leg pain.
These may be indicators of stroke, HTN, embolism, or gallbladder disease. |
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Term
| What are the drug interactions with the contraceptives? |
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Definition
*Lamotrigine: OCs may INCREASE lamotrigine metabolism, therefore decreasing the therapeutic effect
*Selegiline: OCs may DECREASE selegiline metabolism, thereby increasing the therapeutic effect.
*Atorvastatin(HMGCoA Reductase Inhibitors) will INCREASE norethindrone and ethinyl estradiol by 30% and 20% respectively. |
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