Optimizing the choice in oral contraception

1
Optimizing the choice in oral contraception

• PANELISTS

Dr Asha Bhatt Dr Dipti
Patel Dr Bharat Rangani Dr
Tejal Shah Dr Pooja Nadkarni
2
Case 1

• A newly married girl comes to you for information
  about contraception.
• How would you approach this client in terms of
  contraception counselling choice?

3
The Patient InterviewThe Clinicians Priorities

• Recognize the patients goals for control of
  fertility
• Identify the patients health risks that result
  in some methods being preferred over others
• WHO CATEGORY 4
• Determine the patients ability to consistently
  and correctly use the preferred method

4
Teaching Patients About Contraceptive Efficacy

• Why efficacy depends on correct and consistent
  use
• Why methods fail, even with proper use
• Why long-term methods tend to have lower failure
  rates
• Why using two methods simultaneously is more
  effective than using one alone
• Why emergency contraception is a last chance to
  prevent pregnancy

5

• What are the usual barriers to consistent and
  correct use of a contraceptive method?

6
Patient Barriers to Consistent and Correct Use of
a Contraceptive Method

• Experience with the method
• Fears and misunderstandings
• Ability to remember and use the method
• Tolerance of side effects
• Cultural, social, or moral concerns
• Partner (or parental) objections

7

• How can we help in overcoming these barriers?

8
Principles of Effective Counseling

• Listen actively
• Assume nothing
• Objective listening offers a common ground
• Your patient may have more ways to solve her
  problems than you will
• Believe that your patient knows what she wants
• Respect your patients right to privacy

Hatcher R, et al, eds. Contraceptive Technology.
18th rev ed. 2004.
9
Education Tools and Reminder Devices

• Patient information handouts-
• Correcting misperceptions
• Non contraceptive health benefits
• Daily alarm on a computer, personal digital
  assistant (PDA), or cell phone
• Encourage her to call if she has questions or
  concerns

10

• Myths misperceptions??

11
Myths and Misconceptions About Oral Contraceptives

• Cause cancer
• Cause blood clots
• Are associated with weight gain
• Should not be taken by women over the age of 35
• Disrupt an existing pregnancy if taken
  inadverently.
• Makes woman infertile
• Changes sexual behaviour
• Build up in a womans body. Women need a rest
  from taking cocs.

12
Weight Gain and Oral Contraceptives Controlled
Studies Do Not Show Link
Weight gain (?5 lb) in 25 of women no
significant difference between the placebo group
and the users of oral contraceptive (? 50 ?g
ethinyl estradiol EE)
Placebo-controlled double-blind crossover (N380)
Goldzieher et al.,
1971
Prospective, randomized (N49)
Reubinoff et al.,
1995
No association between combination oral
contraceptives and weight gain
Systematic review of randomized controlled trials
Gallo et al.,
2006
Goldzieher JW, et al. Fertil Steril.
197122609-623 Reubinoff BE, et al. Fertil
Steril. 19956351 Gallo MF, et al. Cochrane
Database Syst Rev. 2006(1)CD003987.
13
Drospirenone Has Neutral Effects on Weight
1.0
0.5
0
-0.5
Mean Change in Body Weight (kg)
-1.0
-1.5
-2.0
3
6
7
Month
EE ethinyl estradiol DRSP drospirenone LNG
levonorgestrel
Oelkers W, et al. J Clin Endocrinol Metab.
1995801816-1821.
14
Risks of Oral ContraceptivesNonfatal Venous
Thromboembolism
Estimated Average Risk/ 100,000 Women/Year
Non-Oral Contraceptive Users
Oral Contraceptive Users
Pregnant Women
Food and Drug Administration. FDA Talk Paper.
Nov. 24, 1995.
15
Oral Contraceptives and the Risk of Breast Cancer

• Results of a large epidemiologic study suggest
  that oral contraceptives do not cause breast
  cancer
• Breast cancer risk in women who have not taken
  oral contraceptives for 10 years is the same as
  those who have never used them
• There is a slightly increased risk of diagnosis
  in current users of oral contraceptives and in
  those who stopped taking them 10 years ago
• Tumors are more likely to be localized in oral
  contraceptive users than in nonusers

Collaborative Group on Hormonal Factors in Breast
Cancer. Lancet. 19963471713-1727 Collaborative
Group on Hormonal Factors in Breast Cancer.
Contraception. 1996541S-106S.
16
Noncontraceptive Benefits of Oral Contraceptives

• Improvement of cycle-related conditions
• Acne
• Irregular menstrual cycles
• Dysmenorrhea
• Menorrhagia
• Anemia
• Functional ovarian cysts

• Reduction in cancer of certain organs
• Ovary
• Endometrium
• Colon and rectum

Wallach M, et al., eds. Modern Oral
Contraception Updates from The Contraception
Report. Emron, 2000.
17
Studies Show Oral Contraceptives Reduce the Risk
of Ovarian Cancer
Hildreth et al., 1981 Rosenberg et al., 1982 La
Vecchia et al., 1984 Tzonou et al., 1984 Booth et
al., 1989 Hartge et al., 1989 WHO, 1989 Wu et
al., 1988 Prazzini et al., 1991 Newhouse et al.,
1977 Casagrande et al., 1979 Cramer et al.,
1982 Willet et al., 1981 Weiss, 1981 Risch et
al., 1983 CASH, 1987 Harlow et al., 1988 Shu et
al., 1989 Walnut Creek, 1981 Vessey et al.,
1987 Beral et al., 1988
Summary of relative risk with ever-use of an oral
contraceptive 0.64 (95 CI, 0.57-0.73)
Hospital-Based Case-Control Study
Community-Based Case-Control Study
Cohort Study
0.5
1.0
1.5
2.0
2.5
3.0
3.5
0.0
Relative Risk
Hankinson SE, et al. Obstet Gynecol.
199180708-714.
18
Studies Show Oral Contraceptives Reduce the Risk
of Endometrial Cancer
Horwitz et al., 1979 Weiss et al., 1980 Kaufman
et al., 1980 Kelsey et al., 1982 Hulka et al.,
1982 Henderson et al., 1983 La Vecchia et al.,
1986 Pettersson et al., 1986 CASH,
1987 Koumantaki et al., 1989 WHO, 1991 Brinton et
al., 1983 Jick et al., 1993 Ramcharan et al.,
1981 Trapido, 1983 Beral et al., 1988
Case Control
Cohort
3.5
0.0
0.5
1.0
1.5
2.0
2.5
3.0
Relative Risk
Adapted from Grimes DA, Economy KE. Am J Obstet
Gynecol. 1995172227-235.
19
Oral Contraceptives and Hip FracturesPossible
Risk Reduction
Odds Ratio
Control
Over 40
Under 30
30-39
Age (Y) at First Oral Contraceptive Use
Michaelsson K, et al. Lancet. 19993531481-1484.
20

• Which type of pill would you prefer for this
  healthy newly married girl without any
  contraindications for OCPs?
• Estrogen dose
• Type of progesterone
• Mono/triphasic

21
Estrogen in OCPs

• Low dose
• V.low dose

22
Progestins in Oral Contraceptives
19-Nortestosterone
Spironolactone

• Drospirenone

Estranes
Gonanes

• Norethindrone
• Norethindrone acetate
• Ethynodiol diacetate
• Norethynodrel
• Lynestrenol

• Levonorgestrel
• Norgestrel
• Desogestrel
• Norgestimate
• Gestodene

Not available in the United States.
Adapted from Sulak PJ. OBG Management.
2004Suppl3-8.
23
Phasic Combination Oral Contraceptives

• Triphasic oral contraceptives contain increasing
  doses of estrogen or progestin throughout the
  menstrual cycle in order to decrease adverse
  events
• A Cochrane review of triphasic and monophasic
  oral contraceptives found
• Comparable efficacy
• Suggestion of less spotting, breakthrough
  bleeding, and amenorrhea with triphasic oral
  contraceptives

van Vliet HA, et al. Cochrane Database Syst Rev.
20063CD003553.
24
Case

• A 42 yr old woman on 20 micgm EE pill for last 2
  months comes to you with breakthrough bleeding.
• Expressing concern about ocpills in general at
  her age in particular
• Overall health good,non smoker,no CVS risk
  factors,normotensive, BMI 25

25

• How would you approach her breakthrough bleeding?
• Breakthrough bleeding.. DEFINITION?
• E ? P ?
• 21/7 vs 24/4 vs extended cycle

26

• bleeding that is unscheduled, that occurs outside
  the time of the hormone-free interval, and also
  is not within the first 3 to 4 days of active
  pills within a given OC cycle. Currently, many
  people feel that the better term to use is
  'unscheduled bleeding.'between 10 and 30 of
  women will have some spotting in the first 2
  months of OC use. The high proportion of the
  spotting or abnormal bleeding will usually
  disappear by the third month.

27
Women Who Have an Increased Risk of Breakthrough
Bleeding

• Any woman beginning a new form of hormonal
  contraception
• Women who inconsistently use oral contraceptives
  or miss doses
• Oral contraceptive users who have chlamydial
  cervicitis and/or endometritis
• Infection is the likely cause when breakthrough
  bleeding appears several months after initiating
  an oral contraceptive regimen
• Smokers, possibly because of fluctuations in
  estrogen levels
• Vomiting or diarrhea
• Taking anticonvulsants or rifampicin

Wallach M, et al., eds. Modern Oral
Contraception Updates from The Contraception
Report. 2000.
28
Side Effects Cited for Discontinuation of Oral
Contraceptives
Discontinuing
Rosenberg MJ, et al. Am J Obstet Gynecol.
1998179577-582.
29
Case

• A 20-year-old woman would like to begin OC use,
  but has an older sister whose severe migraine
  headaches began when she started OC use. The
  patient reports a personal history of mild
  headaches occurring 6 to 8 times yearly for the
  past 4 years. These last 3 to 4 hours and are
  bilateral, pressing, or tightening in quality,
  and not associated with nausea, vomiting,
  photophobia, or phonophobia. The headaches
  respond well to over-the-counter medications such
  as NSAIDs. Her neurologic examination is normal
  and there are no other contraindications to OC
  use.

30
Evidence and Guidelines

• Safety. There is no evidence that TTH is a risk
  factor for the development of ischemic stroke.
• Tolerability. There is no evidence that hormonal
  fluctuations play a role in the pathogenesis or
  clinical course of TTH. There is modest evidence
  that a family history of migraine increases the
  risk of developing headache on OCs.
• Guidelines. TTH is not considered a
  contraindication to OC use by any professional
  guidelines.

31
Recommendations

• While the presence of TTH does not contraindicate
  OC use in this patient, the strong family history
  of migraine does increase the risk that she will
  develop new-onset migraine with OC use
• weighing the potential benefits of OC use and the
  strength of other reasons for OC use against the
  small but real risk of headache precipitation

32
Case

• A 23-year-old woman has severe dysmenorrhea that
  has been unresponsive to treatment with NSAIDs.
  She has migraine without aura and takes sodium
  valproate 250 mg twice daily for migraine
  prevention. Because she desires contraception,
  OCs have been recommended as treatment of
  dysmenorrhea. The patient has heard through
  friends and the popular press that because she
  has migraine she should not use OCs. Her
  neurologic examination is normal and she has no
  other contraindications to OC use.

33

• Safety. Migraine and OC use are both risk factors
  for ischemic stroke. The risk of stroke in
  childbearing age women is low, but good quality
  evidence suggests that a diagnosis of migraine
  without aura increases this risk by a factor of
  about 3. The combination of migraine and OC use
  increases the risk of stroke by a factor of about
  14. Stroke risk appears to be higher with OCs
  containing high doses of estrogen (greater than
  50 µg of ethinyl estradiol).

34

• Interestingly, migraine appears to be a risk
  factor for stroke only in women under the age of
  45.

35

• Tolerability. OCs are widely believed to cause or
  aggravate headache, but the evidence that this is
  a common or clinically significant problem is
  remarkably slim.
• Regardless of cause, headache occurring in
  association with OC use tended to improve despite
  continued OC use.

36

• Migraine in women using traditional COCs is more
  likely to occur during the pill-free week,
  presumably triggered by estrogen withdrawal.
• OCs containing lower levels of estrogen may be
  less likely to provoke headache
• There is no evidence that the dose or type of
  progestin in an OC has an important influence on
  headache

37

• Guidelines.
• World Health Organization (WHO) and American
  College of Obstetrics and Gynecology (ACOG)
  guidelines consider that for women under the age
  of 35 who have migraine without aura, and few or
  no cardiovascular risk factors, the benefits of
  OC use typically outweigh the risks

38

• The International Headache Society task force on
  combined OCs and hormone replacement therapy in
  women with migraine concluded that "there is no
  contraindication to the use of COCs in women with
  migraine in the absence of migraine aura or other
  risk factors.

39

• Recommendations
• This patient has migraine without aura, is under
  35, has no additional risk factors for stroke,
  and is likely to experience important improvement
  in another condition from OC use. Avoidance of
  unintended pregnancy is especially important in
  this patient because she is taking valproate, a
  known teratogen.For her, the benefits of OC use
  probably outweigh the drawbacks, and this
  assessment is supported by professional
  guidelines.

40

• It would be wise to obtain a baseline assessment
  of the frequency, severity, and character of this
  patient's headaches and then monitor their
  frequency and severity while she is using OCs.

41
Contraception During Perimenopause Oral
Contraceptives
Estrogen-progestin combinations (8) Progestin-only (8)
Prevent unintended pregnancy Yes
Minimize hormonal fluctuations Yes
Provide additional health benefits Decreased risk of ovarian/ endometrial cancers Bone protection Cycle control
Percentage of women experiencing unintended
pregnancy with typical use within first year of
use.
Grimes DA, Wallach M, eds. Modern Contraception
Updates from The Contraception Report. 1997
Hatcher RA, Nelson AL. In Contraceptive
Technology. 2004391-460.
42
Effect of a Low-Dose Oral Contraceptive
(Minestrin) on Menses During Perimenopause

• Shortened menstrual cycle
• Decreased variability in menses
• Less severe bleeding
• Reduced incidence and duration of
  clotting/flooding

Minestrin 20 µg of ethinyl estradiol plus 1
mg of norethindrone acetate
Casper RF, et al. Menopause. 19974139-147.
43
Effect of a Low-Dose Oral Contraceptive
(Minestrin) on Quality of Life During
Perimenopause

Endpoint in Menopause-Specific Quality-of-Life
Questionnaire
EE ethinyl estradiol NETA norethindrone
acetate
Reproduced with permission from Casper RF, et al.
Menopause. 19974139-147.
44
Oral Contraceptives Maintain Bone Mass in Women
Aged 4149 Years
Bone Mass
Reference Standard
Oral Contraceptives
Control
Months of Use
Shargil AA. Int J Fertil. 19853015-28.
45
Stopping Oral Contraceptives or Transitioning to
Hormone Therapy for Menopause

• Determine when an oral contraceptive is no longer
  needed
• Measure follicle-stimulating hormone and/or
  estradiol levels after being off of oral
  contraceptives for 2 weeks
• Serial elevations in follicle-stimulating hormone
  levels indicate menopause in most women
• Estimate age of menopause based on onset of
  perimenopausal symptoms
• Arbitrarily stop between the ages of 50 and 52
• Transition to hormone therapy may be indicated in
  some women

46
Types of Premenstrual Disorders

• Premenstrual molimina
• Normal premenstrual discomfort, nonproblematic
• Most common premenstrual disorder
• Premenstrual Syndrome (PMS)
• Bothersome adverse somatic and/or affective
  symptoms during the luteal phase
• Premenstrual Dysphoric Disorder (PMDD)
• Significant impairment
• Least common premenstrual disorder

Ginsburg KA, Dinsay R. In Ransom SB, ed.
Practical Strategies in Obstetrics and
Gynecology. Philadelphia W.B. Saunders Company
2000684-694 Kessel B. Obstet Gynecol Clin North
Am. 200027625-639.
47
ACOG Diagnostic Criteria forPremenstrual
Syndrome

• Other disorders must be excluded
• Must include dysfunction in social or economic
  performance
• Symptoms must be present in the absence of
  pharmacologic therapy, hormone ingestion, or drug
  or alcohol use

Affective Symptoms Somatic Symptoms
Irritability Depression Angry outbursts Anxiety Confusion Social withdrawal Breast tenderness Abdominal bloating Headache Swelling of extremities
ACOGAmerican College of Obstetricians and
Gynecologists Limited core of symptoms
Hallmark affective symptom
Adapted from ACOG Practice Bulletin No. 15.
Obstet Gynecol. 200095(4) supplemental
material at end of issue.
48
Premenstrual Dysphoric DisorderSymptoms and
DSM-IV Criteria
Must have 5 symptoms, including at least 1
core symptom Symptoms must occur during the
last week of the luteal phase Symptoms are
relieved within a few days of starting menses
Core Symptoms Depressed mood Anxiety, edginess, nervousness Moodiness Anger or irritability
Other Symptoms Physical symptoms (headache, breast tenderness and/or swelling, bloating, joint/muscle pain, etc.) Fatigue, lethargy Decreased interest in Insomnia/hypersomnia usual activities Difficulty concentrating Feeling overwhelmed/ Appetite changes/cravings out of control
American Psychiatric Association. Diagnostic and
Statistical Manual of Mental Disorders, Fourth
Edition, Text Revision. Washington, DC American
Psychiatric Association, 2000.
49
Validated Tests for Diagnosing PMS and PMDD
Calendar of Premenstrual Experiences (COPE) Symptom calendar 4-point Likert scale 10 physical and 12 behavioral symptoms
Premenstrual Symptoms Screening Tool (PSST) 19-item questionnaire Rating scale with degrees of severity for DSM-IV symptoms
Visual Analogue Scale (VAS) 100-mm vertical line (no symptoms to severe symptoms) Irritability, tension, depression and mood swings
Daily Record of Severity of Problems (DRSP) 24-item questionnaire Symptoms and functional impairment 6-point scale
PMSpremenstrual syndrome PMDDpremenstrual
dysphoric disorder
Feuerstein M, Shaw WS. J Reprod Med.
200276279-289 Steiner M, et al. Arch Women
Ment Health. 20036203-209 Steiner M, et al. J
Affect Disord. 199953269-273 Endicott J, et
al. Arch Womens Ment Health. 2006941-49.
50
Therapies for Premenstrual Syndrome

• Lifestyle changes
• Aerobic exercise
• Dietary modification
• Cognitive-behavioral therapy
• Pharmacologic agents
• Selective serotonin reuptake inhibitors (SSRIs)
• The SSRIs that have an FDA-approved indication
  for treating premenstrual dysphoric disorder are
• Fluoxetine hydrochloride
• Sertraline hydrochloride
• Paroxetine hydrochloride
• Spironolactone
• Anxiolytics
• Gonadotropin-releasing hormone (GnRH) agonists
• Hormonal contraceptives

ACOG Practice Bulletin No. 15. Obstet Gynecol.
200095(4) supplemental material at end of
issue.
51
Lifestyle Changes to Alleviate Symptoms of
Premenstrual Syndrome

• Exercise
• Regular aerobic exercise reduces premenstrual
  syndrome, possibly due to release of endorphins
• Recommendation 2030 minutes/day of aerobic
  exercise at least 3 days per week

• Dietary supplements
• Calcium supplements have modest effects on
  symptoms
• Limited data indicate a possible benefit of a
  beverage containing complex and simple
  carbohydrates

Ginsburg KA, Dinsay R. Premenstrual syndrome. In
Ransom SB, ed. Practical Strategies in Obstetrics
and Gynecology. Philadelphia W.B. Saunders
Company, 2000684-694 Thys-Jacobs S, et al. Am J
Obstet Gynecol. 1998179444-452 Sayegh R, et
al. Obstet Gynecol. 1995 86520-528 Freeman EW,
et al. Int J Gynaecol Obstet. 200277253-254.
52
Cognitive-Behavioral TherapyShort-term
Structured Therapy for PMS
Agent Results
CBT vs. no treatment1 4 weeks of group CBT superior to no treatment (placebo) for reducing PMS severity gains maintained up to 18 months
CBT vs. IFT2 CBT and IFT equally effective for reducing premenstrual levels of negative mood and physical changes effects maintained at 12 months
CBT vs. fluoxetine vs both3 All treatments equally effective at 6 months. Fluoxetine therapy had more rapid effect. No added benefit for combining treatments
CBT vs. no treatment4 CBT more effective than no treatment for reducing PMS symptoms, associated impairments and depression
PMSpremenstrual syndrome CBTcognitive-behaviora
l therapy IFTinformation-focused therapy
(training in relaxation, assertion, and child
management, nutritional/vitamin guidelines,
dietary/lifestyle changes)

1. Taylor D. Res Nurs Health. 199922496-511.
2. Christensen AP, Oei TP. J Affect Disord.
   19953357-63.
3. Hunter MS, et al. J Psychosom Res.
   200253811-817.
4. Blake F, et al. J Psychosom Res. 199845307-318.

53
Spironolactone forPremenstrual Syndrome
Baseline

Plt0.01 vs. baseline Plt0.01 vs. placebo

Spironolactone
Placebo

Visual Analogue Scale

Anxiety, Tension, Irritability, Fatigue,
Depression
Cheerfulness, Well-being, Friendliness,
Energetic Feeling
Headache, Feeling of Swelling, Craving of Sweets,
Breast Tenderness
Wang M, et al. Acta Obstet Gynecol Scand.
199574803-808.
54
Alprazolam for Premenstrual Syndrome

• Anxiolytic agent
• 0.25 mg once or twice daily in luteal phase dose
  should be tapered at menses
• Studies have given inconsistent results
• Contraindicated in women with a history of drug
  abuse or dependence
• Sedation bothersome for some women

ACOG Practice Bulletin No. 15. Obstet
Gynecol. 200095(4) supplemental material at end
of issue.
55
Daily Fluoxetine During the Luteal PhaseImproves
Symptoms of PremenstrualDysphoric Disorder



Plt0.01 Plt0.05
Mean Change from Baseline in Daily Record of
Severity of Symptoms


Fluoxetine 10 mg
Fluoxetine 20 mg
Placebo

DRSPDaily Record of Severity of Problems
Cohen LS, et al. Obstet Gynecol. 2002100435-444.
56
Experience with Hormonal Contraceptives for
Managing Premenstrual Syndrome Symptoms

• Standard estrogen and progestin combination
  contraceptives in a 21/7 regimen show no or
  minimal improvement to symptoms
• Decline in endogenous estradiol levels during the
  last week of hormonal contraception may be
  responsible for the estrogen-withdrawal symptoms
  beginning to appear during the last week, thus
  exacerbating premenstrual-type symptoms during
  the subsequent 7-day hormone-free interval

57
Effect of Oral Contraceptives on Premenstrual
Symptoms in a 21/7 Regimen
Agent Study Type Results
Monophasic ethinyl estradiol/ desogestrel Monophasic ethinyl estradiol/ levonorgestrel Triphasic ethinyl estradiol/ levonorgestrel RCT1 Mood scores improved from baseline for all 3 OCs Benefit no different than that seen with placebo in other studies
? Ethinyl estradiol/norethindrone RCT2 Decreased premenstrual breast pain and bloating compared with placebo No beneficial effect on mood
? Various OCs NCCS3 ? No effect on mood
21/721 days of an active hormone followed by a
7-day hormone-free interval OCoral
contraceptive RCTrandomized, controlled trial
NCCSnested case-control study
1. Backstrom T, et al. Contraception.
199246253-268 2. Graham CA, Sherwin BB. J
Psychosom Res.199236257-266 3. Joffe H, et al.
Am J Obstet Gynecol. 20031891523-1530.
58
Traditional 21/7 Oral Contraceptive Regimen
Associated with Premenstrual Symptoms
Cycle-Related Symptom N262 N262 P Value
Cycle-Related Symptom 21 Active Days 7 Hormone-Free Days P Value
Pelvic pain 21 70 lt0.001
Headache 53 70 lt0.001
Breast tenderness 19 58 lt0.001
Bloating/swelling 16 38 lt0.001
Needing pain meds 43 69 lt0.001
21/721 days of an active hormone followed by a
7-day hormone-free interval
Sulak PJ, et al. Obstet Gynecol. 200095261-266.
59
Drospirenone-Estrogen in an Extended Cycle
(168-day) Regimen Improvement in Premenstrual
Symptoms
28-day cycle
168-day cycle



Average Score on DSR17 Item



Headache
Anxiety
Irritability
Mood Swings
Swelling, Bloating, Weight Gain
Depression
DSR17Penn State Daily Symptom Report
Plt0.0001 P0.0001.
Coffee AL, et al. Am J Obstet Gynecol.
20061951311-1319.
60
Drospirenone-Estrogen 24/4 Regimen Improvement
in PMDD-Related Symptomsas Measured with the
DSRP




Change from Baseline

P0.01 vs. placebo P0.001 vs. placebo

Drospirenone-EE
Placebo



Physical
Mood
Behavioral
Factor scores comprised of individual items from
the Daily Record of Severity of Problems
(DRSP). PMDDpremenstrual dysphoric disorder
EEethinyl estradiol.
Yonkers KA, et al. Obstet Gynecol.
2005106492-501.
61
Family Tree of Contraceptive Progestins
Contraceptive Progestins in Current Use
Not available in the United States.
62
Candidates for Progestin-Only Oral Contraceptives

• Women with contraindications for combination
  hormonal contraceptives, including a history of
• Venous thrombosis
• Vascular disease
• Hypertension
• Heavy smoking (gt35 years)
• Lactating women

Heinemann LA, et al. Eur J Contracept Reprod
Health Care. 1999467-73 Tankeyoon M, et al.
Contraception. 198430505-522.
63
Importance of Correct and ConsistentUse of
Progestin-Only Pills

• The efficacy rate of progestin-only pills is
  comparable to combination oral contraceptives,
  but consistently timed ingestion is required
• Plasma levels fall to baseline after 24 hours
• If ingestion occurs more than 3 hours after a
  required dose, back-up contraception should be
  used for 48 hours

64
Hormone Withdrawal Symptoms with the Traditional
21/7 Oral Contraceptive Regimen
21 Active Days 7 Hormone-free Days P value
Pelvic pain 21 70 lt0.001
Headaches 53 70 lt0.001
Breast tenderness 19 58 lt0.001
Bloating/swelling 16 38 lt0.001
Use of pain meds 43 69 lt0.001
N262
Sulak PJ, et al. Obstet Gynecol. 200095261-266.
65
Approved Regimens That Shorten the Hormone-Free
Interval
Brand Name Estrogen Dose Progestin Dose Regimen
Seasonale 30 µg EE 150 µg levonorgestrel 84/7
SeasoniqueTM 30 µg EE 150 µg levonorgestrel 84/7 7 days 10 µg EE
Yaz 20 µg EE 3 mg drospirenone 24/4
Loestrin 24 Fe 20 µg EE 1 mg norethindrone acetate 24/4 4 days of iron
Lybrel 20 µg EE 90 µg levonorgestrel 365 days (non-cyclic daily dosing)
EE ethinyl estradiol
66
Efficacy, Safety, and Tolerability of an
Extended-Cycle (84/7) Oral Contraceptive Regimen
Discontinuations Due to Adverse Event(s)
Pregnancy
Percentage of Women
Percentage of Women
Conventional
Extended-cycle
Extended-cycle
Conventional
30 µg ethinyl estradiol/150 µg levonorgestrel
Anderson FD, Hait H. Contraception. 20036889-96.
67
Breakthrough Bleeding and SpottingDecrease Over
Time with an Extended-Cycle (84/7) Oral
Contraceptive Regimen
Median Number of Breakthrough Bleeding/Spotting
Days/Cycle
Cycle
Day
1-84
92-175
183-266
274-357
30 µg ethinyl estradiol/150 µg levonorgestrel.
Anderson FD, Hait H. Contraception. 20036889-96.
68
Menstrual Cycle-Related Disorders and Associated
Health Risks

• Ovarian cysts
• Perimenopausal symptomatology
• Shorter cycles
• Cycles further apart and lighter
• Adolescent symptomatology
• Facial acne
• Menorrhagia

• Premenstrual symptomatology
• Menstrual migraine headaches
• Menorrhagia, irregular bleeding
• Anemia
• Endometriosis
• Pain
• Infertility
• Dysmenorrhea

69
Additional Indications forMenstrual Suppression

• Hematologic conditions
• Anemia
• Bleeding disorders
• Clotting defects
• Developmental disabilities
• Professional/social obligations
• Military service
• Professional athletics
• Performing arts (e.g., ballerinas)
• Vacation/honeymoon

70
Hormone-Free IntervalResults in Ovarian Escape
Slide courtesy of Thomas J. Kuehl, PhD
71
Follicular Development Occurs During the
Hormone-Free Interval

• 36 women used triphasic, 30-µg monophasic, or
  20-µg monophasic oral contraceptives for three
  consecutive cycles
• Transvaginal ultrasound was performed every three
  days to monitor ovarian follicular development
• If a follicle reached 14 mm, each subject had a
  daily sonogram and a serum estradiol measurement
• Results Follicles develop to an ovulatory
  diameter during the hormone-free interval

Baerwald AR, et al. Contraception.
200470371-377.
72
Shorter Hormone-Free Intervals Decrease
Follicular Development

• Randomized double-blind study (N60)
• 20 µg ethinyl estradiol (EE)/75 µg gestodene
• 21/7 regimen vs. 23/5 regimen
• 5 cycles (1 pretreatment, 3 treatment, 1
  posttreatment)
• Ovarian suppression, assessed by follicular
  development and EE levels, was more pronounced
  with the 23/5 regimen
• Randomized investigator-blinded controlled trial
  (N54) compared 3 cycles of 3 combination oral
  contraceptives
• 21/7 regimen of 20 µg EE/100 µg levonorgestrel
• 21/2/5 regimen of 20 µg EE/placebo/10 µg EE
• Continuous 20 µg EE/150 µg desogestrel
• The difference among the three groups was
  statistically significant (P0.005)

Spona J, et al. Contraception. 19965471-77.
Schlaff WD, et al. Am J Obstet Gynecol.
2004190943-951.
73
Approved Regimens That Shorten the Hormone-Free
Interval
Brand Name Estrogen Dose Progestin Dose Regimen
Seasonale 30 µg ethinyl estradiol 150 µg levonorgestrel 84/7
SeasoniqueTM 30 µg ethinyl estradiol 150 µg levonorgestrel 84/7 7 days 10 µg ethinyl estradiol
Yaz 20 µg ethinyl estradiol 3 mg drospirenone 24/4
Loestrin 24 Fe 20 µg ethinyl estradiol 1 mg norethindrone acetate 24/4 4 days of iron
74
Managing Breakthrough Bleeding inExtended-Cycle
Oral Contraceptive Regimens

• In a prospective analysis, patients who
  experienced gt7 consecutive days of breakthrough
  bleeding/spotting were counseled to
• Take a 3-day hormone-free interval and resume the
  extended regimen
• OR
• Continue the extended regimen
• If bleeding/spotting was unresolved after seven
  days, take a 3-day hormone-free interval and
  then resume the extended regimen
• All patients whose breakthrough bleeding/spotting
  continued despite either intervention were
  counseled to
• Institute a 3-day hormone-free interval after
  another seven days of bleeding/spotting but not
  before 14 days had passed since the previous
  3-day hormone-free interval

Sulak PJ, et al. Am J Obstet Gynecol.
2006195935-941.
75
Managing Breakthrough Bleeding inExtended-Cycle
Oral Contraceptive Regimens

• Prospective analysis of bleeding among women
  (N111) taking a 21/7 pre-extension regimen
  followed by a 168-day extended regimen of an oral
  contraceptive containing 30 µg ethinyl
  estradiol/3 mg drospirenone
• During the extended cycle
• Continuation of active pills usually resulted in
  continued flow with a greater tendency to require
  a 3-day hormone-free interval
• Taking a 3-day hormone-free interval resulted in
  an initial increase in flow usually followed by a
  cessation of flow after a few days

Sulak PJ, et al. Am J Obstet Gynecol.
2006195935-941.
76
Managing Breakthrough Bleeding inExtended-Cycle
Oral Contraceptive RegimensPatient Counseling
Points

• Patients do not have to adhere to a fixed cycle
  (e.g., 49 days, 91 days)
• Patients should expect breakthrough bleeding and
  spotting. If either occurs, patients should chose
  one of the following options
• Option A
• Keep taking active pills as spotting/bleeding
  will decrease over time
• Option B
• Take a 3- to 4-day hormone-free interval, relabel
  the pill pack to the correct day of the week, and
  restart active pills
• The option chosen should be based on the
  significance of the bleeding/spotting and the
  severity of the hormone withdrawal symptoms a
  patient experiences

77
Extended-Cycle Oral Contraceptive Regimens
Counseling Adolescents

• Adolescents may benefit from a regimented
  extended cycle because they may have difficulty
  determining when to take a hormone-free interval
  (i.e., to allow withdrawal bleeding) if on a
  flexible oral contraceptive schedule
• Consideration of their preferences may promote
  initiation and continuation
• Cost may be an issue, unless the adolescent
  purchases both pills and personal hygiene
  products
• Adolescents must understand that although there
  is a reduction in bleeding days, unscheduled
  bleeding occurs more often, but it decreases with
  continued use

Schwartz JL, et al. Contraception.
199960263-267 den Tonkelaar I, Odden BJ.
Contraception. 199959357-362 Omar H, et al. J
Pediatr Adolesc Gynecol. 200518285-288.
78
Recurrent Endometriosis-Associated Dysmenorrhea
Benefits of anExtended-Cycle Oral Contraceptive
Study population Women who underwent endometriosis surgery within one year Recurrent dysmenorrhea despite cyclic use of oral contraceptives
Intervention Continuous ethinyl estradiol (0.02 mg) and desogestrel (0.15 mg) for two years
Outcomes Reduction in frequency/severity of dysmenorrhea 80 of women satisfied 12 reported relief of menstrual migraines
Vercellini P, et al. Fert Steril. 200380560-563.
79
Preferred Menstrual Frequency
Ages 1824 years (n101)
Ages 2529 years (n45)
Ages 3039 years (n150)
Ages 4049 years (n195)
Percentage of Respondents
Once/ month
Every other month
Once/ 3 months
Once/ 6 months
Once/ year
Never
Association of Reproductive Health
Professionals. Harris Poll, June 14-17, 2002.
80
When compared to a 21/7 regimen,extended
regimens may
Extended Oral Contraceptive Regimens Attitudes
of Health-Care Professionals Toward Associated
Risks
Choices N551
Increase risk of breast cancer 7
Increase risk of deep vein thrombosis/pulmonary embolism 13
Create future fertility problems 3
Affect none of the above 83
Respondents could check multiple responses.
Sulak PJ, et al. Contraception. 20067341-45.
81
Monthly bleeding with standard 21/7 oral
contraceptives
Extended Oral Contraceptive Regimens Attitudes
of Health-Care Professionals Toward Monthly
Bleeding
Choices N551
Has health benefits and is necessary 12
Only serves to reassure a woman that she is not pregnant 49
Is unnecessary and has no health benefits 52
Respondents could check multiple responses.
Sulak PJ, et al. Contraception. 20067341-45.
82
I have recommended altering the standard 21/7
regimen by extending the number of days/weeks of
active pills.No or Yes? (how often)
Extended Oral Contraceptive Regimens Prescribing
Patterns of Health-Care Professionals
Choices N551
No 19
Yes, but rarely 19
Yes, occasionally 36
Yes, frequently 24
Yes 2
Sulak PJ et al. Contraception. 20067341-45.
83
Extended-Cycle Regimens Conclusions

• Current and future extended-cycle contraceptive
  methods will favorably affect menstruation,
  associated hormone-withdrawal symptoms, and
  pregnancy risk
• Decreased incidence of hormone-withdrawal
  symptoms
• Reduced bleeding
• No development of functional ovarian cysts
• Decreased number of unintended pregnancies
• Counseling patients regarding alterations in
  menstruation and safety is critical to initiation
  and continuation of these contraceptive methods
• Breakthrough bleeding and spotting should be
  expected and can be managed
• Long-term risks of such regimens are not known

84
Treatment of Acne

• Systemic Agents
• Oral antibiotics
• Tetracycline
• Minocycline
• Doxycycline
• Clindamycin
• Vitamin A derivatives
• Oral isotretinoin
• Hormonal therapies
• Oral contraceptives
• Spironolactone

• Topical Agents
• Comedolytics
• Retinoids
• Salicylic acid (in many OTC agents)
• Antimicrobials
• Benzoyl peroxide
• Clindamycin
• Erythromycin/
• combination

OTC over the counter
Zaenglein AL, Thiboutot DM. Pediatrics.
20061181188-1199.
85
Acne Treatment Algorithm
Mild Acne Mild Acne Moderate Acne Moderate Acne Severe Nodular Acne
Comedonal Papular/ Pustular Papular/ Pustular Nodular Severe Nodular Acne
First-line Therapy Topical retinoid Topical retinoid BPO or BPO/AB Topical retinoid oral antibiotic BPO or BPO/AB Topical retinoid oral antibiotic BPO or BPO/AB Oral isotretinoin
Alternatives Salicylic acid Oral isotretinoin Topical retinoid oral antibiotic BPO or BPO/AB
Alternatives for Female Patients Hormonal therapy topical retinoid BPO or BPO/AB Hormonal therapy topical retinoid BPO or BPO/AB Hormonal therapy topical retinoid BPO or BPO/AB Hormonal therapy topical retinoid BPO or BPO/AB Hormonal therapy oral antibiotic topical retinoid BPO or BPO/AB
Maintenance Therapy Topical retinoid BPO or BPO/AB Topical retinoid BPO or BPO/AB Topical retinoid BPO or BPO/AB Topical retinoid BPO or BPO/AB Topical retinoid BPO or BPO/AB
AB topical antibiotic BPO benzoyl peroxide
Zaenglein AL, Thiboutot DM. Pediatrics.
20061181188-1199.
86
How Oral Contraceptives Improve Acne

• ? Androgen secretion in the ovaries and adrenal
  glands through their estrogenic effects
• ? Production of testosterone
• ? Levels of free testosterone
• ? Production of dihydrotestosterone
• ? Sex hormone-binding globulin to bind androgens
• ? 5?-reductase activity

van der Vange N, et al. Contraception.
199041345-352 Cassidenti DL, et al. Obstet
Gynecol. 199178103-107.
87
An EE/DRSP Oral Contraceptive Reduces the Number
of Inflammatory Skin Lesions When Compared with
EE/NGM
Inflammatory Lesion Counts
Total Lesion Counts
Mean Change
EE/DRSP EE/NGM
Cycle 6
EE/DRSP ethinyl estradiol 30 µg/drospirenone 3
mg EE/NGMethinyl estradiol 35 µg/norgestimate
180-215-250 µg
Thorneycroft IH, et al. Cutis. 200474123-130.
88
Role of Oral Contraceptives in the Treatment of
Mild to Moderate Acne

• May be more effective for inflammatory lesions
  (papules, pustules, nodules) than noninflammatory
  ones (comedones)
• May be used concurrently with topical agents
• May be used as ongoing maintenance therapy

Thiboutot D. Arch Fam Med. 20009179-187
Usatine RP, et al. Prim Care. 200027289-308
Wallach M, Grimes DA. In Modern Oral
Contraception Updates from The Contraception
Report. 2000155-168.
89
Role of Oral Contraceptives in the Treatment of
Severe Acne

• Before, during, and after isotretinoin
  (Accutane?)
• ...Effective contraception must be used for at
  least 1 month before beginning Accutane therapy,
  during therapy, and for 1 month following
  discontinuation of therapy.
• ...It is critically important that women of
  childbearing potential use two effective forms of
  contraception simultaneously..

Accutane package insert, 2000 (Revised. May
2000).
90
Role of Womens Health Providers in the
Management of Acne

• Treat mild to moderate acne
• Topical/systemic agents as appropriate
• Prescribe oral contraceptives for women with acne
  who also need contraception
• Counsel women that most oral contraceptives
  improve acne for most women
• Counsel women not to discontinue previously
  prescribed topical or oral agents when oral
  contraceptives are initiated
• Refer patients with severe acne to a
  dermatologist
• If the dermatologist prescribes isotretinoin
  (Accutane?), a potential teratogen, counsel women
  on contraception before, during, and after the
  drugs use
• Oral contraceptives provide additional benefits

Accutane package insert, 2000 (Revised. May
2000) Thiboutot D. Arch Fam Med. 20009179-187
Usatine RP, et al. Prim Care. 200027289-308
Wallach M, et al. In Modern Oral Contraception
Updates from The Contraception Report. 2000.
91
(No Transcript)
92

• There have been 3 OCs that have gained FDA
  approval for an indication for the treatment of
  mild-to-moderate acne. As I mentioned before, it
  is the triphasic norgestimate pill, the
  estraphasic norethindrone acetate pill, and most
  recently, the 24-4 20-mcg estrogen/DRSP pill.

93
(No Transcript)
94

• A 37-year-old mother of 2 comes to your office
  because she is interested in starting an OC.
• Her medical history
• a benign fibroadenoma in her left breast 10 years
  ago
• postpartum depression after having her first
  child. Her younger sister was diagnosed with
  breast cancer at the age of 26, but otherwise her
  family history is unremarkable. Her physical
  examination shows BP 129/76 mm Hg, pulse 79 beats
  per minute, BMI 31 kg/m2

95

• Given this patient's age, which of the following
  characteristics would be a reason for not
  recommending a combined OC on the basis of
  current recommendations?