Contraception Part II: Combined Hormonal Contraception and Progestin Only Contraceptives

Question 1

Mechanism of Action of CHC

Release of estrogen in follicular development which builds endometrial lining

Progesterone secreted in last 14 days (not seen in 1st 14 days)
Gettign it ready for pregnancy

CHC - progesterone is adminstered throughout even in first 14 days which is not physiologic

Answer 1

Estrogen:
§ Prevents follicular
development and
ovulation (inhibits FSH)

Progestin:
Synthetic progesterone = progestin
§ Inhibits ovulation (inhibits LH)
§ Thickens cervical mucus – decreases
sperm transport
§ Effects on tubal transport (slow
fallopian tubal motility)
§ atrophic endometrium note:
impaired implantation of fertilized
embryo not demonstrated with CHC

Estrogens less important for contraception
Estrogen important for cycle control

Question 2

Types of Estrogen in CHC Products

Answer 2

§ ethinyl estradiol (EE)
–synthetic estrogen
–longer half life and potency
compared to estradiol
–almost all CHC in Canada contain EE

§ estetrol (E4)
–new product in Canada
–synthetic version of estrogen
produced by human fetal liver

§ estradiol valerate
–not yet available in Canada

Question 3

Types of Progestins in CHC Products

Answer 3

1st generation estranes (testosterone like)
norethindrone, ethynodiol
progesterone, estrogenic, androgenic activity

2nd generation gonanes
norgestrel, levonorgestrel
# progesterone selectivity + androgenic, with less estrogenic activity,
Levononrgestrel is a 2nd gen progestin with highest androgenic effects, potent

3rd generation gonanes desogestrel, norgestimate, norelgestromin, etonorgestrel
less androgenic activity compared to 2nd generation
Note: maintains progesterone selectivity

4th generation drospirenone antimineralocorticoid, antiandrogenic properties

antiandrogenic cyproterone (Main indication for acne, anti androgenic)

Question 4

Non-Contraceptive Benefits of CHC

Answer 4

§ Improved cycle control
– Less dysmenorrhea, PMS
–Decreased menstrual blood loss (less heavy bleeding)
§ Inhibits ovulation:
– Lower incidence ectopic pregnancy, ovarian cysts
§ Improve acne

§ Lower risk of ovarian and endometrialcancer (50% reduction in those cancers after using for 5 years)
§ Decreased risk of colorectal cancer
§ Symptom control in perimenopause (improve hot flashes, night sweat
§ Positive effects on bone mineral density
§ Note: decreased risk of pelvic inflammatory disease unclear – not if chlamydia

Question 5

Medical Risks of CHC
Venous Thromboembolism

Answer 5

§ Estrogens have a dose-dependent procoagulant effect and fibrinolytic balance
- 50ug greater risk, All pdts low dose
§ Risk of VTE is 3 to 4 times higher in women that use COC (with low dose estrogen - <35 μg EE):
–the absolute risk increase is relatively low
• 3 - 5 per 10,000 women/y baseline on women not on CHC (lower risk for younger women i.e. ~1 per 10,000 for 15 – 19 years)

§ Risk is greater in first year.
§ Greater risk with with inherited risk factors for thrombophilia.
§ Also consider other risk factors such as older age, smoking, obesity, recent surgery
§ Differences in VTE risk with various progestins may exist but not all studies consistent.
–Third generation progestins
–Drospirenone, cyproterone

Question 6

when is VTE risk greatest?

Answer 6

Women of reproductive age
baseline risk
3 – 5 per 10, 000 women per year
Women on CHC 8 – 9 per 10,000 women per year (~3 times
increase in risk)
Pregnancy 29 per 10,000 women per year (hypercoagulable)
**Peripartum period 300 – 400 per 10,000 women per year, 6 wks after baby born bihhrdy tidk

Question 7

should cretain progestis be prescribed to lower VTE risks?

Answer 7

§ The role of different progestins on VTE risk is unknown.
§ SOGC does not recommend “preferential prescribing” based on type
of progestins and VTE risk.
Don\t really know which have greater risk
androgenic properies may counteract oriagulant effect of EE

Question 8

Medical Risks of CHC
Myocardial Infarction (MI)
Stroke

Answer 8

§ Rare among young women
§ Dose related – associated with doses of more than 50 μg EE
§ Related to additional risk factors:
–Smoking and age (over 35)
–Hypertension

Question 9

Medical Risk of CHC
Breast Cancer

Answer 9

§ The breast cancer risk remains unclear: some studies report very small increased risk, others no increase.
–More recent studies have found no association with CHC products.
§ Risk associated of CHCs in women with a strong family history is unknown.
- past association based on 50ug

Question 10

Other Risks of CHC
May exacerbate

Answer 10

§ Increase in blood pressure
§ Diabetes – glucose control (More from progestins which compete with insulin receptors)
–likely not a concern with low dose CHC
§ Increase triglycerides (estrogen increase secreted cholesterol in gallbladder)
§ Symptomatic gallbladder disease
§ Migraine headaches

Question 11

Absolute Contraindications

Med eligibility criteria
1 = no contra
2 benefit genrally > risk
3 risk>benefit
4 abs contra

Answer 11

Active or history of VTE
■ Known thrombogenic mutations
■ Major surgery with prolonged immobilization
■ Age >35 years and heavy smoker (> 15 cigs/day)
■ Stroke (history of cerebrovascular disease)
■ Ischemic heart disease
■ Severe hypertension (>160/100mmHg) or with vascular disease
■ Diabetes with complications
■ Liver disease (severe cirrhosis)
■ Pregnancy
■ Breastfeeding (< 6 weeks postpartum)
■ Breast cancer
■ Migraines with aura ( worse if if they have neurologic effects (tingling of arms))

Question 12

contraindications for drospirenone

Answer 12

renal or liver failure, adrenal disease, drugs that
increase K+ levels (ie ACE inhibitors, spironolactone)

Question 13

most common AE with CHC

Answer 13

Breakthrough bleeding is most common side effect of CHC’s

Any kind of bleeding when youre not expecting it
When taking the pill and getting bleed

Fommon in first 7 months, gets better

Question 14

Estrogen related AE

Answer 14

§ nausea
§ breast tenderness
§ fluid retention/edema
§ headaches/migraines
§ chloasma:: change in pigmentation of skin caused by estrogen
§ poor contact lens fit

Question 15

Progestin related AE

Answer 15

§ mood: depression, PMS, fatigue
§ breast tenderness
§ bloating
§ fluid retention
§ increased appetite
§ headache/migraines

Question 16

Androgen side effects

Answer 16

often reported for certain CHCs: (ie acne, hirsutism,
oily skin, increased appetite, weight gain)
§ However androgen side effects are really
not that common with current CHCs.

Question 17

Oral estrogens – can increase sex hormone
binding globulin (SHBG)

what does that cause?

Answer 17

– Leads to a decrease in free
testosterone levels
–Decrease in androgen effects (decrease
acne)
– In some cases may lower libido

Question 18

Deficiency of Hormones with CHC
ometimes side effects may be due to deficiency of hormone:

Answer 18

Estrogen deficiency:
§ early or midcycle spotting, BTB
§ hypomenorrhea
§ mood - irritability, depression
§ menopausal symptoms (i.e.
vasomotor, vaginal dryness)

Progestin deficiency:
§ late BTB/spotting
§ heavy menstrual flows
§ delayed menses

Using this as main estrogen an dprog as the body production stop

Deficiecy as there is not enough of hormones
s

Question 19

Drug Interactions and CHC

Answer 19

Ethinyl estradiol is metabolized by CYP 3A4 (also 2C9, 1A2), then
conjugated with glucuronides.
–EE also undergoes enterohepatic recirculation.
§ Progestins – metabolized by CYP 3A4
–Do not undergo enterohepatic recirculation
§ Clinically significant interactions:
–Inducers of metabolism

Inducers are the main problem, not inhibitors
Could potentially see unintended preg, failure

Question 20

classes of drugs that are inducersof hormone metabolism

Answer 20

Anticonvulsants
HIV meds
antimicrobial (rifampin)
St john’s work
see slide 29

Question 21

why do we need to dose adjust lamotrigine

Answer 21

§ Lamotrigine may need to be dose adjusted after starting CHC.
§ EE induces it’s metabolism ~50% increase in clearance– may see loss of
seizure control
§ Dose of lamotrigine may need to be adjusted starting CHC and after
discontinuing

Question 22

Drug Interactions and CHC
What about antibiotics?

Answer 22

§ Antibiotics can theoretically alter GI flora and therefore interfere with
enterohepatic recirculation of EE.
§ Clinical significance is unknown.

It doesnt affect progestins, should not affect contraceptive effectivness
Thats why sig is unknown
can affect menstrual cycle, breakthrough bkeeding can happen
You cna use backup contraception on abx in case

Question 23

Prescribing CHC: Assess if CHC is Appropriate

Answer 23

-Patient demographics: age, weight, height
-Reasons for use:Contraceptive, non-contraceptive benefits
q-Medical history/medications
-Screen for contraindications
-Screen for VTE, CVD, breast cancer, migraines with aura, disease
-Drug interactions

EE can make migraines worse
Risk with mighraines with aura increases risk of stroke

Question 24

Prescribing CHC: Assessment of Patients
what to ask abt menstrual hx

Answer 24

Social history: smoker

Menstrual history
üAssess menstrual cycle/flow
üDetermine if any undiagnosed vaginal bleeding
Questions to ask: When was last menstrual period, periods regular or irregular? Spotting or bleeding in between? Has it been assessed?

Pregnancy Screen
üRule out the possibility of pregnancy
üWhat questions can you ask to rule out pregnancy?

1. When was your last menstrual period
2. Have you had unprotected intercourse since your last menstrual period Complete pregnancy test if necessary. Refer if possibility of pregnanc

qPrevious use of hormonal contraceptives
üExperience of adverse effects
üSatisfaction with method

qPatients needs
üConvenience/ease of use
üAdherence

Question 25

when to refer for bp?

Answer 25

Perform blood pressure measurement.
REFER if blood pressure >140/90 mmHg

Question 26

Prescribing CHC: Choosing a Product
Estrogen component:

Answer 26

§ all EE products are “low dose” <35 µg EE, lowest EE dose now 10 µg EE
§ Most often start with EE 20 mcg, can adjust dose based on adverse effects or breakthrough bleeding.
§ Canadian Pediatric Position statements recommend starting youth with products of 30 or 35 mcg EE.*
§ For women ≥ 35 years, consider products with < 20 mcg EE.

Youth (Teens to early 20s, recomend 30-35 mch EE
10-20 is too low in some of these indivudials (deficiency)
If choose 20, monitor in 3 months to ensure no deficient

Question 27

Prescribing CHC: Choosing a Product
Progestin component

Answer 27

§ The main variation with CHC is with the progestin
§ Progestins have different potency
– the doses in CHC reflect the differences
in potency
– all progestins are equally effective for contraception

Some clinicians start with a 1st or 2nd generation progestin (Europe, potentially decrease VTE). The SOGC does not recommend preferential prescribing.
§ Consider drospirenone for antimineralocorticoid effects – ie fluid retention, PMS
§ Antiandrogen – cyproterone, drospirenone
– for severe acne

Question 28

The risk of VTWwith combined ormonal contraceptives is:

Answer 28

• Greatest in the first year,
  
  • Dont have evidence that it’s lower with ultralow dose (20ug) CHC, no data
  • Could be higher with 3rd gen progestins but inconclusive

Question 29

Which of the following should be done befre starting a woman on CHC?
- Blood pressure
- Pap smear
Lab test for thrombophilia (not for every individual –> for family history of it with blood clot)

Answer 29

• Correct answer is bp
  Pap smear is not necessary, should be part of normal healt