Classes of Drugs
estrogens
SERMs
progestogens
progesterone agonist/antagonist
androgens
anti-androgens
DEA drug schedule class I
high abuve potential with no accepted medical use *heroin, LSD
DEA drug schedule class II
high potential for abuse, some medical indications with high restrictions (morphine, cocaine, oxycodone)
DEA drug schedule class III
less abuse potential than I and II, all have accepted medical uses (codeine, steroids, marinol)
DEA drug schedule class IV
low potential for abuse, accepted medical uses (benzodiazepines, phenobarbitol)
DEA drug schedule class V
lowest abuse potential (low dose codeine, opium, pregabalin
FDA use in pregnancy ratings category A
B
C
D
X
controlled studies show no risk
no evidence of risk in humans but no controlled studies
risk cannot be ruled out OR animal studies show risk to fetus
positive evidence of risk but benefits may outweigh risks
contraindicated in pregnancy
where do most drugs fall on the FDA use in pregnancy list
category B and C
how is the FDA safe in pregnancy list changing as of 2015
trends in worldwide contraception, what is used most
sterilization 20%
IUD 15%
oral 8%
condom 5%
what types of contraception are used most in developing nations
injectable contraceptives and IUDs
what types of contraception are considered (SC) steroid contraception
oral
patches
nuvaring
intramuscular
progestin IUD
general strategies used to make contraceptives work
block sperm
block ovulation
block sperm access to the cervix
block sperm transit through the uterus
block fallopian tubes
block embryo implantation
types of male contraceptives
permanent (vasectomy)
reversible (barrier contraception, gonadotropin suppression)
how does gonadotropin based male contraception work
what is the failure rate
testosterone enanthate/undeconoate injections to suppress FSH and cause azosperima or oligospermia
2-3%
how long does injected male contraception take to work
what are the draw backs
8-12 weeks to reach 90% azoospermia
requires frequent follow up for injections and semen analysis
how does contraception block ovulation
what drugs use this method
suppression of FSH
steroid contraceptives, GnRH analogs (lupron)
steroid components of contraceptives:
estrogens
progestins
estrogens: ethinyl estradiol (most common), estradiol valerate, mestranol
progestins: >8 forms, 21 carbon deriviatives, 19-notestosterone dervitives, estranes, gonanes
common steroid contracptive doses:
estrogen
progestin
estrogen: 10-50mcg
progestin: 0.15-1mg
adverse side effects of estrogen contraception
increased clotting (increased risk of DVT, MI, CVA)
activaion of RAA cycle (5% risk of HTN, poss fluid retention)
increase in cholestasis
increased risk of endometrial hyperplasia if not given with progestins
mortality related to estrogen use
MI
venous thrombosis
Why are estrogen contraceptives contraindicated for smokers over 35
there is a significant increased risk of MI compared to non-smokers
at what point in using estrogen contraceptives is the risk of venous thrombosis minimal
2 years
T/F Pregnancy is safer than usings OC
false, OC is much safer than pregnancy
issues related to progestin contraception
lipid changes
some are androgenic
can cause dysphoria
lipid changes associated with progestin
Triglycerides and LDL go up, HDL goes down
2 21 carbon progestin choices
how many 19-nortestosterone progestins are there
provera, progesterone
four generations with over dozens of choices
issues with fourth generation progestin contraception
why are GnRH analogs not used to for contraception
because it would cause an extreme loss of estrogen and put women at risk for heart disease and osteoporosis if they aren’t added back
why is ethinyl estradiol the most commonly used estrogenn for OC
because it is well absorbed orally
if a patient presents a medication for oral contraception called mestranol 1/50, what does the 1/50 mean
1 is the dose of progestin, 50 is to dose of estradiol
what are the advantages of combined estrogen/progestin OC
what is the function of progestin
estrogen
highly effective
progestin blocks ovulation and makes cervical unimplantable
estrogen controls uterine bleeding with a 3 weeks on, 1 wk off
T/F period are necessary to maintain health
false, estrogen flucuaton is
methods of oral contraception adminstration
cyclic with a fixed dose or triphasic dose
continuous
why is HTN related to estrogen contraception not as common anymore
because pills used to be much high dose and the risk of HTN is dose dependany
T/F it is possible to take OC continuously without time off for menstruation
true
three types of non-cyclic OCs
seasonale (7 placebos that give 3 periods)
seasonique (only one period at the end)
Lybrel (no periods, continuous
advantages of non-cyclic OCs
less dysmenorrhea and issues with endometriosis
fewer hormone flucuations lead to less premenstrual dysphoria and menstrual migranes
issues with non-cyclic OC use
more total hormone doses mean more exposure and cost
breakthrough bleeding
how to deal with breakthrough bleeding related to non-cyclic OC use
if its mild reassure that patient that all is well
persistent, withdraw treatment for 1 wk then resume
issues with fourth generation progestin use
blocks to effect of aldosterone that prevents fluid retention but increases the risk of hyperkalemia
drospirenone seems to increase thrombosis risk
describe what makes triphasic OCs unique
estrogen and progestins vary during the cycle
mimics a normal cycle
what issues are found with triphasic OCs
some individuals will have menstrual migrains and PMS
what percent of pregnancy are the result of contraceptive failures
how many women miss 1 pill/mo
3/mo
when is it most dangerous to miss a pill
50%
50%
30%
at the beginning of a pill pack
possible issues with contraceptive patches
some patch adhesive reactions
less effective in women over 200lvs
are contraceptive patches safe
yes, early studies show a higher risk of DVT and PE due to higher estradiol levels but recent studies don’t bear that out
what issues are associated with vaginal ring contraceptive use
the ring can fall out
if the ring isn’t inserted on day 1 after the break it can cause failure
if contraception starts on cycle day 1 or 2, when will they take effect
what if you start whenever you want
contraception starts immediately
restart with a new pack after the first period and use condoms until the second pack
side effects related to estrogen oral contraceptives
progestin
breast tenderness, nausea, fluid retention
dysphoria, breast tenderness, oily skin, fat gain
how likley is breakthrough bleeding to occur with OC use
what should you do if this occurs
5-30% in the first two cycles
warn them ahead of time, reassure them
change to a different pill with more estradiol or add a short course of extra extrogen
what challenges are there in prescribing OCs to women under 30
there are compliance issues due to side effects
the side effects don’t outweigh the risk of getting pregnant
what a challenges are found with women over 35 and contraceptive use
they never want to quit, but if they are smoking or have HTN, DM, etc they need to stop
absolute contraindications for OC
smokers after age 35
undiagnosed breast tumors
undiagnosed vaginal bleeding
acute liver disease
history of DVT or hypercoagulation
two factors that will reduce OC efficacy
large body size and drug interactions
drug interactions associated with decreasd OC efficacy
st johns wort
some anti convulsants
anti fungal agents
advantages of OC
reduced quantity and duration of menstrual bleeding
reduced dysmenorrhea
predictable periods or no periods
reduced risk of uterine and ovarian cancer
what happens that makes missing OC pills risky
follicular development is still happening, if the pill isn’t resumed fast enough the follicle may survive and they may ovulate
T/F OC does not effect future fertility
true
where can OC patches NOT be placed
over bony prominences or on your breasts
guidelines to decide which OC to use
match estrogen to body size
use 2nd, 3rd, 4th generation progestin
be familiar with 4-5 brands with different progestins
go with what the patient tells you
general guidelines to match estrogen to body size
15-20 mcg for small to average size women
30-35 mcg for larger women
what is the advantage to starting OC on the first sunday after a period
disadvantage
you will have your period on a monday or tuesday vs the weekend
you have to use condoms for the first month
T/F progestins are more effective than other OCs
issues related
false, they are slightly less effective
irregular bleeding, metabolic changes
choices for long acting reversible contraception (LARC)
injectable progestins
implantable progestins
IUDs
injectable GnRH analogs
side effects related to injectable progestin contraception
bleeding, weight gain, dysphoria
concerns related to injectable progestins
CV/lipid concerns
probably bone loss (Low E2)
female sexual dysfunction from low androgens and dysphoria
types of implantable progestins
side effects
implanon, nexplanon
risks and side effects similar to progestins
how does plan B prevent or dely ovulation
disrupting follicle growth or blunting the LH surge
what is the method of action for IUDs
inflammatory response that blocks the passage of sperm
progestine blockers for emergency contraception uses
mirepristone
ulipristal
will terminate a pregnancy before 7 wks; contraception; used to treat cushings
goals of menopausal hormone support
reduce/prevent hot flashes
improve sleep to improve cognition and reduce depression
prevent bone loss
maintain healt of the GI system
health risks associated with menopause HRT
cardiovascular risk
breast cancer risk increase
probably no help in cognition
five possible treatments of hot flashes
estrogen (high efficacy)
SSRI (moderate to good)
gabapentin (moderate)
progestin (moderate)
clonidine (some help)
two types of vaginal estrogen creams
what are they used for
estradiol and conjugated estrogens
treatment of vaginal atrophy (dysparenunia, urinary incontinence/urgency)
risks of unopposed estrogen
how to fix this
endometrial hyperplasia and carcinoma
if there is a uterus you must add progestin
common methods of estrogen replacement
estradiol (tablets, patch, spray)
conjugated estrogens
+ progesins (combipatch, prempro, fem HRT)
strategy for dosing estrogen for HRT pills
start with a moderate dose that can be titrated up or down based on relief of symptoms
why would you use vaginal vs oral estrogen
vaginal creams for vagina atrophy, orals for hot flashes
is there an advantage to used in progestin on a daily vs cyclic schedule
no, in fact you take a lower total dose with continuous scheduling
three SERMs and their uses
tamoxifen (nolvadex) breast cancer prevention and treatment
raloxifene (evista) osteoporosis
bazedoxifene (duavee) SERM + estrogen for HRT
what is the benefit of giving a SERMs with estrogen for HRT
blocks estrogen receptors in the breast and uterus so there is no need for progestin
should HRT be used for every
no, focus on those with significant hot flashes for 3-5 years