HORMONAL CONTRACEPTION

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HORMONAL CONTRACEPTION

• Micean J. Johnikin MSIV
• Howard University College of Medicine
• Baylor Medicine - Pediatrics Rotation
• January 23 26, 2006

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An Introduction

• Hormonal methods of contraception are very
  reliable and reversible once treatment is
  stopped.
• The most popular hormonal contraceptive are oral
  contraceptives The Pill.
• The leading method of contraception in the United
  States in 2002 (11.6 million women)
• Leading method of contraception in women under 30
• Hormonal alternatives to the pill include
  patches, injections, implants, and the
  progesterone only pill.

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Benefits of Hormonal Contraception

• Highly effective contraception (pregnancy rate
  0.5 1)
• Treatment of hyperandrogenism
• Prevention of ectopic pregnancy
• Some protection against pelvic infection (by
  thickening of the cervical mucous)
• Menstrual cycle disorders including amenorrhea,
  dysmenorrhea and menorrhagia
• Relief of symptoms of premenstrual syndrome

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Historical Perspective

• 1938 Discovery that the addition of an ethinyl
  group to estradiol resulted in both
• An orally active estrogen compound
• A dramatic increase in estrogenic potency
• This compound, ethinyl estradiol, is the estrogen
  in virtually all currently used OCs.

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Historical Perspective (II)

• Ethinyl substitution of testosterone was also
  found to result in an orally active compound
  (ethisterone)
• Removal of the carbon at the C-19 position of
  ethisterone changed it from an androgen to a
  progestin.
• Included in the progestin class norethidrone,
  norethindrone acetate, levonorgestrel.
• Note All of these testosterone derived
  progestins bind to the androgen receptor and have
  some residual androgenic activity.

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Mechanism of Action

• Two types of preparations are used for hormonal
  contraception
• Combinations of estrogens and progestins
• Continuous progestin therapy without concominant
  administration of estrogens
• Estrogen component suppresses ovulation largely
  through selective inhibition of the pituitary
  gland
• Ethinyl estradiol and mestranol are most commonly
  used
• Progestin component produces changes in the
  cervical mucus, the uterine endometrium, and in
  the motility and secretion in the uterine tubes.
• Note The continuous use of progestins alone does
  not always inhibit ovulation.

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Progestin - Only Contraception

• Small amounts of progestins administered orally,
  skin implantation, or injection
• Efficacy comparable to IUDs or combination pills
  containing 20 30 ug of ethinyl estradiol
• Particularly suited for use in patients for whom
  estrogen is undesirable
• High incidence of abnormal bleeding
• The hormonal contraceptives of choice for
  breastfeeding women

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Progestin - Only Pills

• Products containing progestin only (Mini pill)
• Norethindrone or norgestrel
• Deliver a low continuous dosage of hormone
• Taken daily on a continuous schedule
• Example Orvette
• Less effective than the combination pill and may
  produce irregular menstrual cycles

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Progestin Injections

• Effective contraception can also be achieved by
  injections of 150 mg of depot medroxyprogesterone
  acetate (DMPA or DepoProvera) every 3 months.
• After 150 mg dose, ovulation is inhibited for at
  least 14 weeks
• Efficacy comparable to combination pill

Injection into one of the large muscles, such as
the buttocks or upper arm
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Progestin Injections (II)

• Almost all users experience episodes of
  unpredictable spotting and bleeding that decrease
  with time.
• Amenorrhea is common
• Suppression of endogenous estrogen secretion may
  be associated with decreased bone density
• Not desirable for women planning a pregnancy soon
  after cessation of therapy because ovulation
  suppression can persist for as long as 18 months
  after the last injection
• Long term DMPA use reduces menstrual blood loss
  and is associated with decreased risk of
  endometrial cancer

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Progestin Implants

• Insertion of capsules (40mm x 2mm) containing L -
  norgestrel (Norplant) under the skin of the upper
  arm
• Capsules release 1/5 to 1/3 as much steroid as
  oral agents
• Extremely effective, lasting for 5 6 years
• Contraceptive effect is reversed soon after
  implant is removed
• Disadvantages need for surgical insertion and
  removal, some irregular bleeding
• An association with intracranial HTN has been
  observed in a small number of women
• Patients experiencing HA or visual disturbances
  should be checked for papilledema

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Estrogen - Progestin Combination Therapy

• Combination pills are packaged in 21 or 28 day
  cycles. Pills are taken for 21 days followed by a
  7 day withdrawal period to induce menses.
• Last seven pills of a 28 day pack are placebo
  (thought to improve patient compliance)
• Monophasic regimen contain the same dose of
  estrogen and progestin in each of the 21
  hormonally active pills
• Multiphasic preparations were introduced in the
  1970s 80s in an attempt to further lower the
  total steroid dose

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Monophasic Regimen

• Attempts to lower the total dose of steroids have
  resulted in formulation of low dose monophasic
  pills containing a lower daily dose of both
  estrogen and progestin components
• Pills containing less than 50 ug of ethinyl
  estradiol have been referred to as low dose
  pills
• Current pills contain on average 30 35 ug

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Multiphasic Regimens

• Biphasic pills (Ortho 10/11) contains a fixed
  dose of ethinyl estradiol and an increasing dose
  of norethindrone
• Triphasic Regimens (Cyclessa) contain a constant
  low dose of estrogen given over 21 days plus a
  current low but increasing dose of progestin
  given over 3 successive 7 day periods.
• Note While these regimens slightly decrease
  steroid content over the month, they have no
  proven clinical advantage over monophasic
  preparations

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Low Estrogen Dose Preparations

• Contain 20 25 ug of ethinyl estradiol
• Often used for perimenopausal women who want
  contraception with the lowest estrogen dose
  possible
• Provide more than enough estrogen to relieve
  vasomotor flushes
• Examples Mircette, Allesse, Tri Cyclen Lo
• Note Being overweight / obese may increase
  pregnancy risk while on these low dose
  preparations

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New Progestins

• More selective progestins, with less side effects
  and metabolic complications
• Lower affinity for the androgen receptor and
  little effect on serum sex hormone binding
  globulin
• Similar contraceptive efficacy to older OCs
• Examples Ortho Cyclen, Ortho Cept
• Large epidemiologic trials have reported
  increased DVT risk with these newer OCs

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Spironolactone Analogues

• Drospirenone (DRSP), a new progestin, is derived
  from 17 alpha sprinolactone
• Progestongenic, anti- androgenic, and anti
  mineralcorticoid activity
• Yasmin is the first formulation to contain DRSP,
  is a monophasic oral contraceptive containing 30
  ug of ethinyl estradiol and 3 mg of DRSP
• In a randomized trial of 900 women, Foidart et al
  reported a mean body weight decrease in women
  assigned Yasmin therapy

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Contraceptive Patches Rings

• The contraceptive skin patch (Evra) is a small
  (1.75 sq in) adhesive patch worn on the skin. It
  is worn for 3 weeks out of every four.
• The vaginal ring is a flexible, plastic ring that
  is placed in the upper vagina. The ring releases
  both estrogen and progestin continuously. It is
  worn for 21 days, removed for 7 days and then a
  new ring is inserted.

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Emergency Contraception

• Back up method of birth control that can be
  used to reduce the likelihood of pregnancy after
  unprotected sex or known contraceptive failure
• When treatment is begun within 72 hours it is 99
  effective
• Two products
• Preven ( Norgestrel 0.5 mg with ethinyl estradiol
  0.05 mg) Four tablets (2 tablets immediately and
  2 after 12 hours)
• Plan B (L Norgestrel 0.75 mg) Twice daily for
  1 day
• Often administered with anti - emetics

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Prescription Considerations
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Screening Requirements

• Hormonal contraception can be safely provided
  after
• Careful medical history
• Blood pressure measurement
• Note breast exams, pap smears and STD screening
  are generally considered not necessary before a
  first prescription of OCs.

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Missed Pills

• Common cause of contraceptive failure
• Hormonally active pill should be taken as soon as
  possible when a pill has been missed
• WHO recommends that no back up or emergency
  contraception is necessary unless three or more
  30 35 mcg ethinyl estradiol pills have been
  forgotten

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ACOG Recommendations for Hormonal Contraception
in Breastfeeding Women

• Progestin only oral contraceptives prescribed
  or dispensed at discharge from the hospital to be
  started 2 3 weeks postpartum (i.e. the first
  Sunday after the newborn is 2 weeks old)
• Depot medroxyprogesterone acetate initiated at 6
  weeks postpartum
• Hormonal implants inserted at 6 weeks postpartum
• Combined estrogen progestin contraceptives, if
  prescribed should not be started before 6 weeks
  postpartum, only when lactation is well
  established and the infants nutritional status
  well monitored.

There are certain clinical situations in which
earlier initiation might be considered.
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Drug Interactions

• The metabolism of OCs is accelerated by any drug
  that increases liver microsomal enzyme activity
• Phenobarbital
• Phenytoin
• Griseofulvin
• Rifampin
• WHO suggests that women taking anti convulsants
  including phenytoin, carbamazepine, barbituates,
  primidone, topiramate or oxcarbazepine should not
  use hormonal contraception.

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Oral Contraceptives Contraindications Cautions

• Contraindicated
• Thromobphlebitis
• Thromboembolic phenomena
• Cerebrovascular disorders
• Breast tumor / estrogen dependent neoplasm
• Pregnancy
• Undiagnosed abnormal uterine bleeding

• Avoid or use with caution
• Liver disease
• Asthma
• Eczema
• Migraine
• DM
• HTN
• Optic neuritis
• Convulsive disorders

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Question 1

• Which of the following would be an appropriate
  hormonal contraceptive for a female to begin 2
  weeks post partum?
• Cyclessa
• Mircette
• Ortho Tri Cyclen
• Orvette
• Yasmin

Only progestin only oral contraceptives should
be prescribed or dispensed at discharge from the
hospital to be started 2 3 weeks postpartum.
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Question 2

• Which of the following is required before the
  prescription of OCs?
• Breast exam
• Careful history
• EKG
• Pap smear
• STD screening

Hormonal contraception can be safely provided
after 1)Careful medical history 2)Blood pressure
measurement
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Question 3

• Which drug below is has not been shown to cause
  drug interactions with OCs?
• Barbituates
• Carbamazepine
• Gabapentin
• Griseofulvin
• Phenytoin

Anticonvulsants that do not appear to reduce
contraceptive efficacy Gabapentin Lamotrigine Tia
gabine
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Mild Adverse Effects with O.C. Use

• Mild Nausea, mastalgia, breakthrough bleeding
  and edema are related to the amount of estrogen
  in the preparation
• Effects can often be alleviated by a shift to a
  preparation containing smaller estrogens or to
  agents containing progestins with more androgenic
  effects
• Withdrawal bleeding failure
• Most often with combination preparations
• May be confused with pregnancy
• May try a different preparation or other
  contraceptive methods if disturbing to patient.

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Moderate Adverse Effects

• Moderate any of the following may require
  discontinuation
• Breakthrough bleeding most common problem in
  using progestational agents alone (25)
• Combination pills with higher levels of progestin
  and estrogen
• Biphasic and triphasic O.C.s decrease
  breakthrough bleeding without increasing total
  hormonal content
• Weight gain more common with combination agents
  containing androgen like progestins
• Shift to products with less androgen effects
• Amenorrhea following cessation
• Patients with menstrual irregularities before
  taking O.C. are particularly susceptible
• Check prolactin levels (patients may also have
  galactorrhea)
• Other effects acne, hirsutism, increased skin
  pigmentation

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Severe Adverse Affects

• Venous Thromboembolic Disease
• Incidence related to the estrogen component
• Antithrombin III is substantially decreased with
  O.C. use
• Risk increased during the first month of O.C. use
  and remains constant for several years or more.
  Risk returns to normal with one month of
  discontinuation.
• Myocardial Infarction
• Higher risk in smokers, the obese, history of
  preeclampsia / HTN, hyperlipoproteinemia, DM
• Progestin decreases HDL
• Net effect depends on pill composition
• Cerebrovascular Disease
• Increased risk in women gt35, current O.C. users
• SAH incidence may increase with time
• Other effects cholestatic jaudice, hepatic
  adenomas, depression

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REFERENCES

• Hormonal Contraception. BUPA Health Information
  Team, November 2003
• Contraceptive Use and Methods in the U.S. Fact
  Sheet. Henry J. Kaiser Family Foundation June
  2003
• Use of Contraception and Use of Family Planning
  Services in the United States 1982 2002. CDC
  National Center for Health Statistics December
  10, 2004
• Contraception While Breastfeeding. American
  College of Obstetrics and Gynecologists
• Basic Clinical Pharmacology 8th Ed. Katzung