Pharmacology of Hormonal Contraception

Question 1

What type and what amounts are typically available in combined hormonal contraceptives?

Answer 1

ethanol estradiol in 20, 30-35 and 50mcgs quantities

Question 2

How do progestins used in combined hormonal contraceptives differ?

Answer 2

progestins vary largely not eh basis of specificity to progesterone receptors as they can activate both progesterone and androgen receptors

Question 3

Name projection that have lower vs. higher specificity for progesterone receptor (typically newer).

Answer 3

lower specificity: norenthindrone/norenthidrone acetate/ethynodiol
levonrgestrel
medoxyprogesterone acetate
norgestrel

higher specificity:
norgestimate
desogestrel/etonogestrel
drospirenone (also has anti-mineral corticoid activity)

Question 4

How do estrogen and progesterone work to suppress FSH and LH?

Answer 4

estrogen acts as negative feedback to FSH and progestin acts as negative feedback on LH pulses and spike

lack of follicular development and ovulation prevent pregnancy

Question 5

What additional physiological/ anatomical mechanisms does progestrin cause to reduce fertility?

Answer 5

decreased tubal function (motility and secretion)
cervix/mucus less permeable to sperm (more viscous)
diminished endometrial responsiveness to implantation

Question 6

How is progestin used in treatment of PCOS?

Answer 6

progestin component of HC suppresses GnRH pulse frequency, which prevents the preferential secretion of LH and suppresses ovarian androgen production

Question 7

How is estrogen used in treatment of PCOS?

Answer 7

estrogen surpasses FSH, leading to decreased ovarian follicular development/function and decreases ovarian steroid production (including androgen)

Question 8

What is the mechanism by which HC treated hypothalamic amenorrhea?

Answer 8

HC provides estrogen which increases bone density and withdrawal of progestin can cause shedding of endometrium (limit overgrowth)

progestin only HC lead to endometrial glandular atrophy

Question 9

Why are HC used to treat uterine fibroids and migraines?

Answer 9

HC can limit endometrial buildup and limit frequency of menses

HC mechanism in migraine and premenstrual dysphoric disorder treatment is not fully understood, thought to reduce fluctuation in hormones that can trigger migraines

Question 10

How do HCs improve risk in ovarian and endometrial cancer?

Answer 10

HC suppress ovulation (ovarian cancer) and progestin-mediated suppression of estrogen induced proliferation of endometrium (endometrial cancer)

Question 11

How do HCs provide benefit in acne or anemia?

Answer 11

estrogen increases SHBG decreasing free testosterone that increases acne

anemia is decreased due to suppression of menstrual blood loss

also seen are reduction in ovarian cysts and decrease in fibrocystic breast changes

Question 12

By what mechanism does HC increase the risk of MI?

Answer 12

acceleration of athrogenesis possible, although progesterone (decrease) and estrogen (increase) effects on HDL tend to balance out

up to 5% of women may develop hypertension when on combined HC via activation of the RAAS

Question 13

What are absolute contraindications for combined HC in women older than 35?

Answer 13

tobacco use and/or uncontrolled hypertension

note a personal history of any thromboembolic event is considered an absolute contraindication to use of combined HC

Question 14

How does HC increase the risk of venous thromboembolic disease?

Answer 14

it increases factors VII, VIII, IX and X with a substantial decrease in antithrombin III leading to increased

Question 15

Describe the 4 most common dosing regimens/formulations of HC.

Answer 15

monophonic pills (estrogen and progestin consistent)
biphasic pills (estrogen and progestin vary 1st and 2nd halves of the cycle)
triphasic pills (vary the dose or type of the progestin every 5-10d)
extended cycle (3 packs without placebo week) used to avoid unpleasant symptoms of menstruation or avoid migraines)

Question 16

What are examples of other extended dose routes of HC?

Answer 16

weekly transdermal patch (has a risk of higher steady state and lower peak)
combined estrogen/progestin vaginal rink (worn 3 of 4 weeks)- increased risk of MI and thrombotic complications by 2.5 (RR)

Question 17

When are progestin only pills a good option?

Answer 17

in women with contraindication to estrogen: prior thromboembolic disease or tobacco use over 35y

in postpartum women who wish to breastfeed

*progestin not as consistent in suppression of ovulation but still includes effects on mucus, endometrium and oviduct motility

Question 18

What are the risks and benefits of progestin only injectables?

Answer 18

benefits: decrease menses, cramps, decrease risk of PID
risks: menstrual irregularities (endometrium is not stabilized), weight gain and reversible decreased bone density

Question 19

What type of hormones are included in intrauterine devices?

Answer 19

intrauterine devices like Mirena release 20g of levonorgestrel (only) per 24hrs for up to 5 years

must be inserted by a health professional and may cause some mild cramping and discomfort

Question 20

What is formulation of emergency contraception and how do patients have access to these treatments?

Answer 20

functions as a high dose progestin (only) that disrupts follicular growth, blocks LH surge, reduces endometrium and tubal transport of sperm/ova

is most effective when used as soon after intercourse as possible