TABLE C1. Classifications for progestin-only contraceptives, including implants, depot medroxyprogesterone acetate, and progestin-only pills.
| Condition | Category |
Clarification/Evidence/Comment | |||||
|---|---|---|---|---|---|---|---|
| Implant |
DMPA |
POP |
|||||
|
Personal
Characteristics and Reproductive History
| |||||||
|
Pregnancy
|
NA |
NA |
NA |
Clarification: Use of
POCs is not required. No known harm to the patient, the course
of pregnancy, or the fetus occurs if POCs are inadvertently used
during pregnancy. However, the relation between DMPA use during
pregnancy and its effects on the fetus remains
unclear. |
|||
|
Age
|
Evidence:
Most studies have found that women lose BMD during DMPA use but
recover BMD after discontinuation (4). Limited evidence
demonstrates a weak association with fracture. However, one
large study suggests that women who choose DMPA might be at
higher risk for fracture before initiation (5). It is
unclear whether adult women with long durations of DMPA use can
regain BMD to baseline levels before entering menopause and
whether adolescents can reach peak bone mass after
discontinuation of DMPA. The relation between these changes in
BMD during the reproductive years and future fracture risk is
unknown. Studies generally find no effect of POCs other than
DMPA on BMD (4–52). |
||||||
| a. Menarche to <18
years |
1 |
2 |
1 |
||||
| b. 18–45
years |
1 |
1 |
1 |
||||
| c. >45 years |
1 |
2 |
1 |
||||
|
Parity
| |||||||
| a. Nulliparous |
1 |
1 |
1 |
— |
|||
| b. Parous |
1 |
1 |
1 |
— |
|||
|
Breastfeeding
| |||||||
| a. <21 days
postpartum |
2 |
2 |
2 |
Clarification
(breastfeeding): Breastfeeding provides important
health benefits for breastfeeding parent and infant. The U.S.
Dietary Guidelines for Americans and American Academy of
Pediatrics recommend that infants be exclusively breastfed for
about the first 6 months with continued breastfeeding while
introducing appropriate complementary foods for 1 year or longer
(53)
or up to age 2 years or longer (54). Evidence (breastfeeding): Two small, RCTs found no adverse impact on breastfeeding with initiation of etonogestrel implants within 48 hours postpartum. Other studies found that initiation of POPs, injectables, and implants at ≤6 weeks postpartum compared with nonhormonal use had no detrimental effect on breastfeeding outcomes or infant health, growth, and development in the first year postpartum. In general, these studies are of poor quality, lack standard definitions of breastfeeding or outcome measures, and have not included premature or ill infants (55,56). Evidence: Limited evidence suggests that DMPA use might further elevate risk for VTE among postpartum women compared with non-use (Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516). Comment: Risk factors for breastfeeding difficulties include previous breastfeeding difficulties, certain medical conditions, certain perinatal complications, and preterm birth. For all breastfeeding persons, with or without breastfeeding difficulties, discussions about contraception should include information about risks, benefits, and alternatives. |
|||
| b. 21 to
<30 days postpartum |
Clarification
(breastfeeding): Breastfeeding provides important
health benefits for breastfeeding parent and infant. The U.S.
Dietary Guidelines for Americans and American Academy of
Pediatrics recommend that infants be exclusively breastfed for
about the first 6 months with continued breastfeeding while
introducing appropriate complementary foods for 1 year or longer
(53)
or up to age 2 years or longer (54). Evidence (breastfeeding): Two small, RCTs found no adverse impact on breastfeeding with initiation of etonogestrel implants within 48 hours postpartum. Other studies found that initiation of POPs, injectables, and implants at ≤6 weeks postpartum compared with nonhormonal use had no detrimental effect on breastfeeding outcomes or infant health, growth, and development in the first year postpartum. In general, these studies are of poor quality, lack standard definitions of breastfeeding or outcome measures, and have not included premature or ill infants (55,56). Evidence: Limited evidence suggests that DMPA use might further elevate risk for VTE among postpartum women compared with nonuse (Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516). Comment: Risk factors for breastfeeding difficulties include previous breastfeeding difficulties, certain medical conditions, certain perinatal complications, and preterm birth. For all breastfeeding persons, with or without difficulties, discussions about contraception should include information about risks, benefits, and alternatives. |
||||||
| i. With
other risk factors for VTE (e.g., age ≥35 years, previous
VTE, thrombophilia, immobility, transfusion at delivery,
peripartum cardiomyopathy, BMI ≥30 kg/m2,
postpartum hemorrhage, postcesarean delivery, preeclampsia, or
smoking) |
2 |
2 |
2 |
||||
| ii.
Without other risk factors for VTE |
2 |
2 |
2 |
||||
| c.
30–42 days postpartum |
Clarification
(breastfeeding): Breastfeeding provides important
health benefits for breastfeeding parent and infant. The U.S.
Dietary Guidelines for Americans and American Academy of
Pediatrics recommend that infants be exclusively breastfed for
about the first 6 months with continued breastfeeding while
introducing appropriate complementary foods for 1 year or longer
(53)
or up to age 2 years or longer (54). Evidence (breastfeeding): Two small, RCTs found no adverse impact on breastfeeding with initiation of etonogestrel implants within 48 hours postpartum. Other studies found that initiation of POPs, injectables, and implants at ≤6 weeks postpartum compared with nonhormonal use had no detrimental effect on breastfeeding outcomes or infant health, growth, and development in the first year postpartum. In general, these studies are of poor quality, lack standard definitions of breastfeeding or outcome measures, and have not included premature or ill infants (55,56). Evidence: Limited evidence suggests that DMPA use might further elevate risk for VTE among postpartum women compared with nonuse (Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516). Comment: Risk factors for breastfeeding difficulties include previous breastfeeding difficulties, certain medical conditions, certain perinatal complications, and preterm birth. For all breastfeeding persons, with or without breastfeeding difficulties, discussions about contraception should include information about risks, benefits, and alternatives. |
||||||
| i. With
other risk factors for VTE (e.g., age ≥35 years, previous
VTE, thrombophilia, immobility, transfusion at delivery,
peripartum cardiomyopathy, BMI ≥30 kg/m2,
postpartum hemorrhage, postcesarean delivery, preeclampsia, or
smoking) |
1 |
2 |
1 |
||||
| ii.
Without other risk factors for VTE |
1 |
1 |
1 |
||||
| d. >42 days
postpartum |
1 |
1 |
1 |
Clarification
(breastfeeding): Breastfeeding provides important
health benefits for breastfeeding parent and infant. The U.S.
Dietary Guidelines for Americans and American Academy of
Pediatrics recommend that infants be exclusively breastfed for
about the first 6 months with continued breastfeeding while
introducing appropriate complementary foods for 1 year or longer
(53)
or up to age 2 years or longer (54). Evidence: Overall, studies found that initiation of POPs, injectables, and implants at >6 weeks postpartum compared with nonhormonal use had no detrimental effect on breastfeeding outcomes or infant health, growth, and development in the first year postpartum. In general, these studies are of poor quality, lack standard definitions of breastfeeding or outcome measures, and have not included premature or ill infants (56). Comment: Risk factors for breastfeeding difficulties include previous breastfeeding difficulties, certain medical conditions, certain perinatal complications, and preterm birth. For all breastfeeding persons, with or without breastfeeding difficulties, discussions about contraception should include information about risks, benefits, and alternatives. |
|||
|
Postpartum
(nonbreastfeeding) | |||||||
| a. <21 days
postpartum |
1 |
2 |
1 |
Evidence: Limited
evidence suggests that DMPA use might further elevate risk for
VTE among postpartum women compared with nonuse (Supplementary
Appendix, https://stacks.cdc.gov/view/cdc/156516). |
|||
| b.
21–42 days postpartum | |||||||
| i. With
other risk factors for VTE (e.g., age ≥35 years, previous
VTE, thrombophilia, immobility, transfusion at delivery,
peripartum cardiomyopathy, BMI ≥30 kg/m2,
postpartum hemorrhage, postcesarean delivery, preeclampsia, or
smoking) |
1 |
2 |
1 |
Evidence: Limited
evidence suggests that DMPA use might further elevate risk for
VTE among postpartum women compared with nonuse (Supplementary
Appendix, https://stacks.cdc.gov/view/cdc/156516). |
|||
| ii.
Without other risk factors for VTE |
1 |
1 |
1 |
— |
|||
| c. >42 days
postpartum |
1 |
1 |
1 |
— |
|||
|
Postabortion
(spontaneous
or
induced) | |||||||
| a. First
trimester abortion |
Clarification: POCs may be started immediately
after abortion completion or at time of medication abortion
initiation. Clarification (DMPA): After a first trimester medication abortion that did not include mifepristone, there is no restriction for the use of DMPA (category 1). After a first trimester medication abortion that included mifepristone, there is no restriction for use of DMPA after abortion completion (category 1) and benefits generally outweigh risks with DMPA use immediately at time of medication abortion initiation (category 2). Concurrent administration of DMPA with mifepristone might slightly decrease medication abortion effectiveness and increase risk for ongoing pregnancy. Risk for ongoing pregnancy with concurrent administration of DMPA with mifepristone should be considered along with personal preference and access to follow-up abortion and contraceptive care. Evidence: Limited evidence suggests decreased first trimester medication abortion effectiveness with concurrent administration of DMPA with mifepristone (immediate) versus DMPA administration after abortion completion (delayed). In one study, the risk for ongoing pregnancy, while overall low, was higher with immediate (3.6%) versus delayed (0.9%) DMPA administration (difference 2.7%; 90% CI = 0.4–5.6%) (57). This difference was not seen with other progestin-only methods (58). Evidence suggests that there is no increased risk for adverse events when POCs are initiated after first trimester procedural or medication abortion (immediately or delayed) (58) (Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516). |
||||||
| i.
Procedural (surgical) |
1 |
1 |
1 |
||||
| ii.
Medication |
1 |
1/2 |
1 |
||||
| iii.
Spontaneous abortion with no intervention |
1 |
1 |
1 |
||||
| b. Second
trimester abortion |
Clarification: POCs may be started immediately
after abortion completion or at time of medication abortion
initiation. |
||||||
| i.
Procedural (surgical) |
1 |
1 |
1 |
||||
| ii.
Medication |
1 |
1 |
1 |
||||
| iii.
Spontaneous abortion with no intervention |
1 |
1 |
1 |
||||
| c. Immediate postseptic
abortion |
1 |
1 |
1 |
Clarification: POCs may
be started immediately after abortion completion or at time of
medication abortion initiation. |
|||
|
Past ectopic
pregnancy
|
1 |
1 |
2 |
Comment: POP users have a
higher absolute rate of ectopic pregnancy than do users of other
POCs but still lower than those using no method. |
|||
|
History of pelvic
surgery
|
1 |
1 |
1 |
— |
|||
|
Smoking
| |||||||
| a. Age <35
years |
1 |
1 |
1 |
— |
|||
| b. Age
≥35 years | |||||||
| i. <15
cigarettes per day |
1 |
1 |
1 |
— |
|||
| ii.
≥15 cigarettes per day |
1 |
1 |
1 |
— |
|||
|
Obesity
| |||||||
| a. BMI ≥30
kg/m2 |
1 |
1 |
1 |
— |
|||
| b. Menarche to <18
years and BMI ≥30 kg/m2 |
1 |
2 |
1 |
Evidence: Among adult
women, generally no association has been found between baseline
weight and weight gain among DMPA users compared with nonusers.
Evidence is mixed for adolescent DMPA users, with certain
studies observing greater weight gain among users with obesity
compared with those without obesity but other studies
demonstrating no association; methodologic differences across
studies might account for the differences in findings. Data on
other POC methods and other adverse outcomes including weight
gain are limited (59–76). |
|||
|
History
of bariatric
surgery This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 3). | |||||||
| a. Restrictive procedures:
decrease storage capacity of the stomach (vertical banded
gastroplasty, laparoscopic adjustable gastric band, or
laparoscopic sleeve gastrectomy) |
1 |
1 |
1 |
Evidence: Limited
evidence demonstrated no substantial decrease in effectiveness
of oral contraceptives among women who underwent laparoscopic
placement of an adjustable gastric band (77). |
|||
| b. Malabsorptive
procedures: decrease absorption of nutrients and calories by
shortening the functional length of the small intestine
(Roux-en-Y gastric bypass or biliopancreatic
diversion) |
1 |
1 |
3 |
Evidence: Limited
evidence demonstrated no substantial decrease in effectiveness
of oral contraceptives among women who underwent a
biliopancreatic diversion; however, evidence from
pharmacokinetic studies suggested conflicting results regarding
oral contraceptive effectiveness among women who underwent a
jejunoileal bypass (77). Comment: Bariatric surgical procedures involving a malabsorptive component have the potential to decrease oral contraceptive effectiveness, perhaps further decreased by postoperative complications such as long-term diarrhea, vomiting, or both. |
|||
|
Surgery
| |||||||
| a. Minor surgery without
immobilization |
1 |
1 |
1 |
— |
|||
| b. Major
surgery | |||||||
| i. Without
prolonged immobilization |
1 |
1 |
1 |
— |
|||
| ii. With
prolonged immobilization |
1 |
2 |
1 |
Evidence: No direct
evidence was identified on risk for thrombosis with POC use
among those undergoing major surgery. Use of DMPA, which has
been associated with a higher risk for venous thrombosis
compared with nonuse (Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516), might
further elevate risk for thrombosis among persons with prolonged
immobilization after major surgery. |
|||
|
Cardiovascular Disease
| |||||||
|
Multiple risk
factors for atherosclerotic cardiovascular disease
(e.g., older age, smoking, diabetes, hypertension, low HDL, high
LDL, or high triglyceride levels) |
2 |
3 |
2 |
Clarification: When
multiple major risk factors exist, risk for cardiovascular
disease might increase substantially. Certain POCs might
increase the risk for thrombosis, although this increase is
substantially less than with COCs. The effects of DMPA might
persist for some time after
discontinuation. Clarification: The recommendations apply to known pre-existing medical conditions or characteristics. Few if any screening tests are needed before initiation of contraception. See U.S. SPR (https://www.cdc.gov/contraception/hcp/usspr) (1). |
|||
|
Hypertension Systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥100 mm Hg are associated with increased risk for adverse health events as a result of pregnancy (Box 3). | |||||||
| a. Adequately controlled
hypertension |
1 |
2 |
1 |
Clarification: For all
categories of hypertension, classifications are based on the
assumption that no other risk factors exist for cardiovascular
disease. When multiple risk factors do exist, risk for
cardiovascular disease might increase substantially. A single
reading of blood pressure level is not sufficient to classify a
person as hypertensive. Clarification: Persons adequately treated for hypertension are at lower risk for acute myocardial infarction and stroke than are untreated persons. Although no data exist, POC users with adequately controlled and monitored hypertension should be at lower risk for acute myocardial infarction and stroke than are untreated hypertensive POC users. |
|||
| b. Elevated
blood pressure
levels (properly
taken
measurements) |
Clarification: For all categories of
hypertension, classifications are based on the assumption that
no other risk factors exist for cardiovascular disease. When
multiple risk factors do exist, risk for cardiovascular disease
might increase substantially. A single reading of blood pressure
level is not sufficient to classify a person as
hypertensive. Evidence: Limited evidence suggests that among women with hypertension, those who used POPs or progestin-only injectables had a small increased risk for cardiovascular events compared with women who did not use these methods (78). |
||||||
| i.
Systolic 140–159 mm Hg or diastolic 90–99 mm
Hg |
1 |
2 |
1 |
||||
| ii.
Systolic ≥160 mm Hg or diastolic ≥100 mm
Hg |
2 |
3 |
2 |
||||
| c. Vascular
disease |
2 |
3 |
2 |
Clarification: For all
categories of hypertension, classifications are based on the
assumption that no other risk factors exist for cardiovascular
disease. When multiple risk factors do exist, risk for
cardiovascular disease might increase substantially. A single
reading of blood pressure level is not sufficient to classify a
person as hypertensive. Comment: Concern exists about hypoestrogenic effects and reduced HDL levels, particularly among users of DMPA. However, little concern exists about these effects with regard to POPs. The effects of DMPA might persist for some time after discontinuation. |
|||
|
History of high
blood pressure during pregnancy (when current blood
pressure is measurable and normal) |
1 |
1 |
1 |
— |
|||
|
Deep
venous thrombosis/
Pulmonary
embolism This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 3). | |||||||
| a. Current or history of
DVT/PE, receiving anticoagulant therapy (therapeutic dose)
(e.g., acute DVT/PE or long-term therapeutic dose) |
2 |
2 |
2 |
Clarification: Persons
using anticoagulant therapy are at risk for gynecologic
complications of therapy, such as heavy or prolonged bleeding
and hemorrhagic ovarian cysts. POCs can be of benefit in
preventing or treating these complications; benefits might vary
by POC dose and formulation. When a contraceptive method is used
as a therapy, rather than solely to prevent pregnancy, the
risk/benefit ratio might differ and should be considered on a
case-by-case basis. Evidence: Limited evidence was identified on use of POCs among women with acute DVT/PE receiving anticoagulant therapy (Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516 In one study among women with a history of acute VTE currently receiving therapeutic anticoagulant therapy (i.e., rivaroxaban or enoxaparin/vitamin K antagonist [warfarin or acenocoumarol]), the incidence of recurrent VTE was similar among estrogen users (CHC or estrogen-only pills), POC users, and women not on hormonal therapy (79). Limited evidence suggests that intramuscular injections of DMPA in women receiving chronic anticoagulation therapy do not pose a significant risk for hematoma at the injection site or increase the risk for heavy or irregular vaginal bleeding (80). |
|||
| b. History of
DVT/PE,
receiving anticoagulant
therapy
(prophylactic dose) |
Clarification: Persons using anticoagulant
therapy are at risk for gynecologic complications of therapy,
such as heavy or prolonged bleeding and hemorrhagic ovarian
cysts. POCs can be of benefit in preventing or treating these
complications; benefits might vary by POC dose and formulation.
When a contraceptive method is used as a therapy, rather than
solely to prevent pregnancy, the risk/benefit ratio might differ
and should be considered on a case-by-case
basis. Evidence: Limited evidence was identified on use of POCs among women with acute DVT/PE receiving anticoagulant therapy (Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516). Use of DMPA, which has been associated with a higher risk for venous thrombosis compared with nonuse (Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516), might further elevate risk for thrombosis among persons with a history of DVT/PE and at higher risk for recurrent DVT/PE. Limited evidence suggests that intramuscular injections of DMPA in women receiving chronic anticoagulation therapy do not pose a significant risk for hematoma at the injection site or increase the risk for heavy or irregular vaginal bleeding (80). |
||||||
| i. Higher
risk for recurrent DVT/PE (one or more risk factors) |
2 |
3 |
2 |
||||
| •
Thrombophilia (e.g., factor V Leiden mutation; prothrombin gene
mutation; protein S, protein C, and antithrombin deficiencies;
or antiphospholipid
syndrome) • Active cancer (metastatic, receiving therapy, or within 6 months after clinical remission), excluding nonmelanoma skin cancer • History of recurrent DVT/PE | |||||||
| ii. Lower
risk for recurrent DVT/PE (no risk factors) |
2 |
2 |
2 |
||||
| c. History of
DVT/PE, not
receiving
anticoagulant
therapy | |||||||
| i. Higher
risk for recurrent DVT/PE (one or more risk factors) |
2 |
3 |
2 |
Evidence: Use
of DMPA, which has been associated with a higher risk for venous
thrombosis compared with nonuse (Supplementary Appendix,
https://stacks.cdc.gov/view/cdc/156516), might
further elevate risk for thrombosis among persons with a history
of DVT/PE and at higher risk for recurrent DVT/PE. |
|||
| • History of
estrogen-associated
DVT/PE • Pregnancy-associated DVT/PE • Idiopathic DVT/PE • Thrombophilia (e.g., factor V Leiden mutation; prothrombin gene mutation; protein S, protein C, and antithrombin deficiencies; or antiphospholipid syndrome) • Active cancer (metastatic, receiving therapy, or within 6 months after clinical remission), excluding nonmelanoma skin cancer • History of recurrent DVT/PE | |||||||
| ii. Lower
risk for recurrent DVT/PE (no risk factors) |
2 |
2 |
2 |
— |
|||
| d. Family
history
(first-degree relatives) |
1 |
1 |
1 |
— |
|||
|
Thrombophilia
(e.g., factor V Leiden mutation; prothrombin gene mutation;
protein S, protein C, and antithrombin deficiencies; or
antiphospholipid syndrome)
This condition is associated
with increased risk for adverse health events as a result of
pregnancy (Box
3). |
2 |
3 |
2 |
Clarification: Routine
screening in the general population before contraceptive
initiation is not
recommended. Clarification: If a person has current or history of DVT/PE, see recommendations for DVT/PE. Clarification: Classification of antiphospholipid syndrome includes presence of a clinical feature (e.g., thrombosis or obstetric morbidity) and persistently abnormal antiphospholipid antibody test on two or more occasions at least 12 weeks apart (81). Evidence: Among women with factor V Leiden mutation, one study found that women using POCs had an increased risk for venous thrombosis compared with non-users without the mutation, with the highest relative risk for DMPA users (82). Women with prothrombin gene mutation using POCs did not have an increased risk for venous thrombosis compared with nonusers without the mutation (82). No evidence was identified on POC use among persons with protein S deficiency, protein C deficiency, antithrombin deficiency, or antiphospholipid syndrome (Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516). |
|||
|
Superficial venous
disorders
| |||||||
| a. Varicose
veins |
1 |
1 |
1 |
— |
|||
| b. Superficial venous
thrombosis (acute or history) |
1 |
2 |
1 |
Evidence: No direct
evidence was identified on risk for thrombosis with POC use
among persons with superficial venous thrombosis (Supplementary
Appendix, https://stacks.cdc.gov/view/cdc/156516). Persons
with superficial venous thrombosis are at higher risk for venous
thrombosis than the general population (83). Use of DMPA, which
has been associated with a higher risk for venous thrombosis
compared with non-use (Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516), might
further elevate risk for thrombosis among persons with acute or
history of superficial venous thrombosis. |
|||
|
Current
and history of ischemic heart disease This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 3). |
Initiation |
Continuation |
Initiation |
Continuation |
Comment:
Concern exists about hypoestrogenic effects and reduced HDL
levels, particularly among users of DMPA. However, little
concern exists about these effects with regard to POPs. The
effects of DMPA might persist for some time after
discontinuation. |
||
| 2 |
3 |
3 |
2 |
3 |
|||
|
Stroke (history of cerebrovascular
accident) This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 3). |
Initiation |
Continuation |
Initiation |
Continuation |
Comment:
Concern exists about hypoestrogenic effects and reduced HDL
levels, particularly among users of DMPA. However, little
concern exists about these effects with regard to POPs. The
effects of DMPA might persist for some time after
discontinuation. |
||
| 2 |
3 |
3 |
2 |
3 |
|||
|
Valvular
heart disease Complicated valvular heart disease is associated with increased risk for adverse health events as a result of pregnancy (Box 3). | |||||||
| a. Uncomplicated |
1 |
1 |
1 |
— |
|||
| b. Complicated (pulmonary
hypertension, risk for atrial fibrillation, or history of
subacute bacterial endocarditis) |
1 |
2 |
1 |
Evidence: No direct
evidence was identified on risk for thrombosis with POC use
among persons with valvular heart disease (Supplementary
Appendix, https://stacks.cdc.gov/view/cdc/156516). Use of
DMPA, which has been associated with a higher risk for venous
thrombosis compared with nonuse (Supplementary Appendix,
https://stacks.cdc.gov/view/cdc/156516), might
further elevate risk for thrombosis among persons with
complicated valvular heart disease. |
|||
|
Peripartum
cardiomyopathy This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 3). |
Evidence: No
direct evidence was identified on the safety of POC use among
persons with peripartum cardiomyopathy (Supplementary Appendix,
https://stacks.cdc.gov/view/cdc/156516). Limited
indirect evidence from noncomparative studies of women with
cardiac disease demonstrated few cases of hypertension,
thromboembolism, and heart failure in women with cardiac disease
using POPs and DMPA (84). Use of DMPA, which has
been associated with a higher risk for venous thrombosis
compared with nonuse (Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516), might
further elevate risk for thrombosis among persons with
peripartum cardiomyopathy. Comment: Progestin-only implants might induce cardiac arrhythmias in healthy persons; persons with peripartum cardiomyopathy have a high incidence of cardiac arrhythmias. |
||||||
| a. Normal or
mildly
impaired cardiac function
(New York
Heart
Association Functional
Class I or II: no
limitation
of activities or slight,
mild
limitation of activity) (85) | |||||||
| i. <6
months |
1 |
2 |
1 |
||||
| ii.
≥6 months |
1 |
2 |
1 |
||||
| b. Moderately or severely
impaired cardiac function (New York Heart Association Functional
Class III or IV: marked limitation of activity or should be at
complete rest) (85) |
2 |
3 |
2 |
||||
|
Renal
Disease
| |||||||
|
Chronic
kidney disease This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 3). | |||||||
| a. Current nephrotic
syndrome |
2 |
3 |
2 DRSP POP with known hyperkalemia: 4 |
Clarification (DRSP POP):
Persons with known hyperkalemia should not use DRSP POPs because
of the risk for worsening hyperkalemia (category 4). For persons
with CKD without known hyperkalemia (category 2), consider
checking serum potassium level during first cycle of DRSP
POPs. Evidence: No direct evidence was identified on POC use among persons with CKD with current nephrotic syndrome (Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516). Persons with severe CKD or nephrotic syndrome are at higher risk for thrombosis than the general population (86–90). Use of DMPA, which has been associated with increased risk for thrombosis compared with nonuse (Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516), might further elevate risk for thrombosis among those with CKD with current nephrotic syndrome. Persons with severe CKD have a higher prevalence of fracture than the general population (91–93). Use of DMPA, which has been associated with small changes in bone mineral density (4) might further elevate risk for fracture among persons with CKD with current nephrotic syndrome. Comment: A person might have CKD without current nephrotic syndrome, but might have other conditions often associated with CKD (e.g., diabetes, hypertension, SLE). See recommendations for other conditions if they apply. |
|||
| b. Hemodialysis |
2 |
3 |
2 DRSP POP with known hyperkalemia: 4 |
Clarification (DRSP POP):
Persons with known hyperkalemia should not use DRSP POPs because
of the risk for worsening hyperkalemia (category 4). For persons
with CKD without known hyperkalemia (category 2), consider
checking serum potassium level during first cycle of DRSP
POPs. Evidence: No direct evidence was identified on POC use among persons with CKD on hemodialysis (Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516). Persons with CKD on dialysis are at higher risk for thrombosis than the general population (94-96). Use of DMPA, which has been associated with increased risk for thrombosis compared with nonuse (Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516), might further elevate risk for thrombosis among those with CKD on dialysis. Persons with CKD on dialysis have a higher prevalence of fracture than the general population (97–99). Use of DMPA, which has been associated with small changes in bone mineral density (4), might further elevate risk for fracture among persons with CKD on dialysis. Comment: A person might have CKD without hemodialysis, but might have other conditions often associated with CKD (e.g., diabetes, hypertension, SLE). See recommendations for other conditions if they apply. |
|||
| c. Peritoneal
dialysis |
2 |
3 |
2 DRSP POP with known hyperkalemia: 4 |
Clarification (DRSP POP):
Persons with known hyperkalemia should not use DRSP POPs because
of the risk for worsening hyperkalemia (category 4). For persons
with CKD without known hyperkalemia (category 2), consider
checking serum potassium level during first cycle of DRSP
POPs. Evidence: No direct evidence was identified on POC use among persons with CKD on peritoneal dialysis (Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516). Persons with CKD on dialysis are at higher risk for thrombosis than the general population (94–96). Use of DMPA, which has been associated with increased risk for thrombosis compared with nonuse (Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516), might further elevate risk for thrombosis among those with CKD on dialysis. Persons with CKD on dialysis have a higher prevalence of fracture than the general population (97–99). Use of DMPA, which has been associated with small changes in bone mineral density (4), might further elevate risk for fracture among persons with CKD on dialysis. Comment: A person might have CKD without peritoneal dialysis but might have other conditions often associated with CKD (e.g., diabetes, hypertension, and SLE). See recommendations for other conditions if they apply. |
|||
|
Rheumatic Diseases
| |||||||
|
Systemic
lupus
erythematosus This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 3). |
Initiation |
Continuation |
— |
||||
| a. Positive (or unknown)
antiphospholipid antibodies |
2 |
3 |
3 |
2 |
Clarification: Persons
with SLE are at increased risk for ischemic heart disease,
stroke, and VTE. Categories assigned to such conditions in U.S.
MEC should be the same for persons with SLE who have these
conditions. For all subconditions of SLE, classifications are
based on the assumption that no other risk factors for
cardiovascular disease are present; these classifications
must be modified in the presence of such risk factors (100–118). Evidence: No direct evidence was identified on POC use among persons with SLE with antiphospholipid antibodies (119) (Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516). Persons with SLE with antiphospholipid antibodies are at higher risk for thrombosis than the general population (120,121). Use of DMPA, which has been associated with a higher risk for venous thrombosis compared with nonuse (Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516), might further elevate risk for thrombosis among persons with SLE with antiphospholipid antibodies. |
||
| b. Severe
thrombocytopenia |
2 |
3 |
2 |
2 |
Clarification: Persons
with SLE are at increased risk for ischemic heart disease,
stroke, and VTE. Categories assigned to such conditions in U.S.
MEC should be the same for persons with SLE who have these
conditions. For all subconditions of SLE, classifications are
based on the assumption that no other risk factors for
cardiovascular disease are present; these classifications must
be modified in the presence of such risk factors (100–118). Comment: Severe thrombocytopenia increases the risk for bleeding. POCs might be useful in treating heavy or prolonged bleeding in persons with severe thrombocytopenia. However, given the increased or erratic bleeding that might be seen on initiation of DMPA and its irreversibility for 11–13 weeks after administration, initiation of this method in persons with severe thrombocytopenia should be done with caution. |
||
| c. Immunosuppressive
therapy |
2 |
2 |
2 |
2 |
Clarification: Persons
with SLE are at increased risk for ischemic heart disease,
stroke, and VTE. Categories assigned to such conditions in U.S.
MEC should be the same for persons with SLE who have these
conditions. For all subconditions of SLE, classifications are
based on the assumption that no other risk factors for
cardiovascular disease are present; these classifications must
be modified in the presence of such risk factors (100–118). |
||
| d. None of the
above |
2 |
2 |
2 |
2 |
Clarification: Persons
with SLE are at increased risk for ischemic heart disease,
stroke, and VTE. Categories assigned to such conditions in U.S.
MEC should be the same for persons with SLE who have these
conditions. For all subconditions of SLE, classifications are
based on the assumption that no other risk factors for
cardiovascular disease are present; these classifications must
be modified in the presence of such risk factors (100–118). |
||
|
Rheumatoid arthritis
| |||||||
| a. Not receiving
immunosuppressive therapy |
1 |
2 |
1 |
Evidence: Limited
evidence demonstrates no consistent pattern of improvement or
worsening of rheumatoid arthritis with use of oral
contraceptives, progesterone, or estrogen (122). |
|||
| b. Receiving
immunosuppressive therapy |
1 |
2/3 |
1 |
Clarification (DMPA):
DMPA use among persons receiving long-term corticosteroid
therapy with a history of, or with risk factors for,
nontraumatic fractures is classified as category 3. Otherwise,
DMPA use for persons with rheumatoid arthritis is classified as
category 2. Evidence: Limited evidence demonstrates no consistent pattern of improvement or worsening of rheumatoid arthritis with use of oral contraceptives, progesterone, or estrogen (122). |
|||
|
Neurologic Conditions
| |||||||
|
Headaches
| |||||||
| a. Nonmigraine (mild or
severe) |
1 |
1 |
1 |
— |
|||
| b.
Migraine |
Evidence: No
studies directly examined the risk for stroke among women with
migraine using POCs (123). Limited evidence
demonstrated that women using POPs, DMPA, or implants do not
have an increased risk for ischemic stroke compared with
nonusers (124). Comment: Menstrual migraine is a subtype of migraine without aura. For more information, see the International Headache Society’s International Classification of Headache Disorders, 3rd ed. (https://ichd-3.org) (125). |
||||||
| i. Without
aura (includes menstrual migraine) |
1 |
1 |
1 |
||||
| ii. With
aura |
1 |
1 |
1 |
||||
|
Epilepsy This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 3). |
1 |
1 |
1 |
Clarification: If a
person is taking anticonvulsants, see recommendations for Drug
Interactions. Certain anticonvulsants lower POC
effectiveness. |
|||
|
Multiple
sclerosis
|
Evidence:
Limited evidence demonstrates that use of COCs or oral
contraceptives (type not specified) among women with multiple
sclerosis does not worsen the clinical course of disease (126). Comment: Persons with multiple sclerosis might have compromised bone health from disease-related disability, immobility, and use of corticosteroids. Use of DMPA, which has been associated with small changes in BMD, might be of concern. |
||||||
| a. Without prolonged
immobility |
1 |
2 |
1 |
||||
| b. With prolonged
immobility |
1 |
2 |
1 |
||||
|
Depressive Disorders
| |||||||
|
Depressive
disorders
|
1 |
1 |
1 |
Clarification: If a
person is taking psychotropic medications or St. John’s
wort, see recommendations for Drug
Interactions. Evidence: The frequency of psychiatric hospitalizations for women with bipolar disorder or depression did not significantly differ among women using DMPA, LNG-IUD, Cu-IUD, or sterilization (127). |
|||
|
Reproductive Tract Infections and
Disorders
| |||||||
|
Vaginal
bleeding patterns
| |||||||
| a. Irregular pattern
without heavy bleeding |
2 |
2 |
2 |
Comment: Irregular
menstrual bleeding patterns are common among healthy persons.
POC use frequently induces an irregular bleeding pattern.
Implant use might induce irregular bleeding patterns, especially
during the first 3–6 months, although these patterns
might persist longer. |
|||
| b. Heavy or prolonged
bleeding (includes regular and irregular patterns) |
2 |
2 |
2 |
Clarification: Unusually
heavy bleeding should raise the suspicion of a serious
underlying condition. |
|||
|
Unexplained vaginal
bleeding (suspicious for serious condition) before
evaluation |
3 |
3 |
2 |
Clarification: If
pregnancy or an underlying pathological condition (e.g., pelvic
malignancy) is suspected, it must be evaluated and the category
adjusted after evaluation. Comment: POCs might cause irregular bleeding patterns, which might mask symptoms of underlying pathologic conditions. The effects of DMPA might persist for some time after discontinuation. |
|||
|
Endometriosis
|
1 |
1 |
1 |
— |
|||
|
Benign ovarian
tumors (including cysts) |
1 |
1 |
1 |
— |
|||
|
Severe
dysmenorrhea
|
1 |
1 |
1 |
— |
|||
|
Gestational
trophoblastic
disease This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 3). |
Clarification: For all subconditions of
gestational trophoblastic disease, classifications are based on
the assumption that persons are under close medical supervision
because of the need for monitoring of β-hCG levels for
appropriate disease surveillance. |
||||||
| a. Suspected
gestational
trophoblastic
disease
(immediate
postevacuation) | |||||||
| i. Uterine
size first trimester |
1 |
1 |
1 |
||||
| ii.
Uterine size second trimester |
1 |
1 |
1 |
||||
| b. Confirmed
gestational
trophoblastic disease
(after initial
evacuation
and during monitoring) | |||||||
| i.
Undetectable or nonpregnant β–hCG levels |
1 |
1 |
1 |
||||
| ii.
Decreasing β–hCG levels |
1 |
1 |
1 |
||||
| iii.
Persistently elevated β-hCG levels or malignant disease,
with no evidence or suspicion of intrauterine disease |
1 |
1 |
1 |
||||
| iv.
Persistently elevated β-hCG levels or malignant disease,
with evidence or suspicion of intrauterine disease |
1 |
1 |
1 |
||||
|
Cervical
ectropion
|
1 |
1 |
1 |
— |
|||
|
Cervical
intraepithelial neoplasia
|
2 |
2 |
1 |
Evidence: Among women
with persistent human papillomavirus infection, long-term DMPA
use (≥5 years) might increase the risk for carcinoma in
situ and invasive carcinoma (128). |
|||
|
Cervical
cancer (awaiting treatment) |
2 |
2 |
1 |
Comment: Theoretical
concern exists that POC use might affect prognosis of the
existing disease. While awaiting treatment, POCs may be used. In
general, treatment of this condition can render a person
infertile. |
|||
|
Breast
disease Breast cancer is associated with increased risk for adverse health events as a result of pregnancy (Box 3). | |||||||
| a. Undiagnosed
mass |
2 |
2 |
2 |
Clarification: Evaluation
of mass should be pursued as early as possible. |
|||
| b. Benign breast
disease |
1 |
1 |
1 |
— |
|||
| c. Family history of
cancer |
1 |
1 |
1 |
— |
|||
| d. Breast
cancer | |||||||
| i.
Current |
4 |
4 |
4 |
Comment:
Breast cancer is a hormonally sensitive tumor, and the prognosis
for persons with current or recent breast cancer might worsen
with POC use. |
|||
| ii. Past
and no evidence of current disease for 5 years |
3 |
3 |
3 |
||||
|
Endometrial
hyperplasia
|
1 |
1 |
1 |
— |
|||
|
Endometrial
cancer This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 3). |
1 |
1 |
1 |
Comment: While awaiting
treatment, POCs may be used. In general, treatment of this
condition renders a person infertile. |
|||
|
Ovarian
cancer This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 3). |
1 |
1 |
1 |
Comment: While awaiting
treatment, POCs may be used. In general, treatment of this
condition renders a person infertile. |
|||
|
Uterine
fibroids
|
1 |
1 |
1 |
Comment: POCs do not
appear to cause growth of uterine fibroids. |
|||
|
Pelvic
inflammatory disease
|
Comment:
Whether POCs, like COCs, reduce the risk for PID among persons
with STIs is unknown; however, they do not protect against HIV
infection or lower genital tract STIs. |
||||||
| a. Current PID |
1 |
1 |
1 |
||||
| b. Past
PID | |||||||
| i. With
subsequent pregnancy |
1 |
1 |
1 |
||||
| ii.
Without subsequent pregnancy |
1 |
1 |
1 |
||||
|
Sexually
transmitted
infections
| |||||||
| a. Current purulent
cervicitis or chlamydial infection or gonococcal
infection |
1 |
1 |
1 |
— |
|||
| b. Vaginitis (including
Trichomonas vaginalis and bacterial
vaginosis) |
1 |
1 |
1 |
— |
|||
| c. Other factors related
to STIs |
1 |
1 |
1 |
— |
|||
|
HIV
| |||||||
|
High risk for HIV
infection
|
1 |
1 |
1 |
Evidence: High-quality
evidence from one RCT observed no statistically significant
differences in HIV acquisition between DMPA-IM versus Cu-IUD,
DMPA-IM versus LNG implant, and Cu-IUD versus LNG implant. Of
the low-to-moderate-quality evidence from 14 observational
studies, certain studies suggested a possible increased risk for
HIV infection with progestin-only injectable use, which was most
likely due to unmeasured confounding. Low-quality evidence from
three observational studies did not suggest an increased HIV
infection risk for implant users. No studies of sufficient
quality were identified for POPs (129–131). |
|||
|
HIV
infection For persons with HIV infection who are not clinically well or not receiving ARV therapy, this condition is associated with increased risk for adverse health events as a result of pregnancy (Box 3). |
1 |
1 |
1 |
Clarification: Drug
interactions might exist between hormonal contraceptives and ARV
drugs (see recommendations for Drug
Interactions). Evidence: Overall, evidence does not support an association between POC use and progression of HIV infection. Limited direct evidence on an association between POC use and transmission of HIV to noninfected partners, as well as studies measuring genital viral shedding as a proxy for infectivity, have had mixed results. Studies measuring whether hormonal contraceptive methods affect plasma HIV viral load generally have found no effect (132–134). |
|||
|
Other
Infections
| |||||||
|
Schistosomiasis Schistosomiasis with fibrosis of the liver is associated with increased risk for adverse health events as a result of pregnancy (Box 3). | |||||||
| a. Uncomplicated |
1 |
1 |
1 |
Evidence: Among women
with uncomplicated schistosomiasis, limited evidence
demonstrated that DMPA use had no adverse effects on liver
function (135). |
|||
| b. Fibrosis of the liver
(if severe, see recommendations for Cirrhosis) |
1 |
1 |
1 |
— |
|||
|
Tuberculosis This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 3). |
Clarification: If a person is taking rifampin,
see recommendations for Drug Interactions. Rifampin is likely to
decrease the effectiveness of certain POCs. |
||||||
| a. Nonpelvic |
1 |
1 |
1 |
||||
| b. Pelvic |
1 |
1 |
1 |
||||
|
Malaria
|
1 |
1 |
1 |
— |
|||
|
Endocrine Conditions
| |||||||
|
Diabetes Insulin-dependent diabetes; diabetes with nephropathy, retinopathy or neuropathy; diabetes with other vascular disease; or diabetes of >20 years’ duration are associated with increased risk for adverse health events as a result of pregnancy (Box 3). | |||||||
| a. History of gestational
disease |
1 |
1 |
1 |
Evidence: POCs
had no adverse effects on serum lipid levels in
women with a history of gestational diabetes in two small
studies (136,137).
Limited evidence is inconsistent about the development of
noninsulin-dependent diabetes among users of POCs with a history
of gestational diabetes (138–141). |
|||
| b. Nonvascular
disease |
Evidence:
Among women with insulin-dependent or noninsulin-dependent
diabetes, limited evidence on use of POCs (POPs, DMPA, and LNG
implant) suggests that these methods have little effect on
short-term or long-term diabetes control (e.g., glycosylated
hemoglobin levels), hemostatic markers, or lipid profile (142–145). |
||||||
| i.
Non-insulin dependent |
2 |
2 |
2 |
||||
| ii.
Insulin dependent |
2 |
2 |
2 |
||||
| c. Nephropathy,
retinopathy or neuropathy |
2 |
3 |
2 |
Comment: Concern exists
about hypoestrogenic effects and reduced HDL levels,
particularly among users of DMPA. The effects of DMPA might
persist for some time after discontinuation. Certain POCs might
increase the risk for thrombosis, although this increase is
substantially less than with COCs. |
|||
| d. Other vascular disease
or diabetes of >20 years’ duration |
2 |
3 |
2 |
Comment: Concern exists
about hypoestrogenic effects and reduced HDL levels,
particularly among users of DMPA. The effects of DMPA might
persist for some time after discontinuation. Certain POCs might
increase the risk for thrombosis, although this increase is
substantially less than with COCs. |
|||
|
Thyroid
disorders
| |||||||
| a. Simple goiter |
1 |
1 |
1 |
— |
|||
| b. Hyperthyroid |
1 |
1 |
1 |
— |
|||
| c. Hypothyroid |
1 |
1 |
1 |
— |
|||
|
Gastrointestinal Conditions
| |||||||
|
Inflammatory bowel
disease (ulcerative colitis or Crohn’s
disease) |
1 |
2 |
2 |
Evidence: Risk for
disease relapse among women with IBD using oral contraceptives
(most studies did not specify formulation) did not increase
significantly from that for nonusers (146). Comment: Absorption of POPs among persons with IBD might be reduced if the person has substantial malabsorption caused by severe disease or small bowel surgery. Women with IBD have a higher prevalence of osteoporosis and osteopenia than the general population. Use of DMPA, which has been associated with small changes in BMD, might be of concern. |
|||
|
Gallbladder disease
| |||||||
| a. Asymptomatic |
2 |
2 |
2 |
— |
|||
| b.
Symptomatic | |||||||
| i.
Current |
2 |
2 |
2 |
— |
|||
| ii.
Treated by cholecystectomy |
2 |
2 |
2 |
— |
|||
| iii.
Medically treated |
2 |
2 |
2 |
— |
|||
|
History
of cholestasis
| |||||||
| a. Pregnancy
related |
1 |
1 |
1 |
|
|||
| b. Past COC
related |
2 |
2 |
2 |
Comment: Theoretical
concern exists that a history of COC-related cholestasis might
predict subsequent cholestasis with POC use. However, this has
not been documented. |
|||
|
Viral
hepatitis
| |||||||
| a. Acute or
flare |
1 |
1 |
1 |
Evidence: No direct
evidence was identified on POC use among persons with viral
hepatitis (Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516). |
|||
| b. Chronic |
1 |
1 |
1 |
Evidence: No evidence was
identified on POC use among persons with viral hepatitis
(Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516). |
|||
|
Cirrhosis Decompensated cirrhosis is associated with increased risk for adverse health events as a result of pregnancy (Box 3). | |||||||
| a. Compensated (normal
liver function) |
1 |
1 |
1 |
Evidence: No direct
evidence was identified on POC use among persons with cirrhosis
(Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516). |
|||
| b. Decompensated (impaired
liver function) |
2 |
3 |
2 |
Evidence: No direct
evidence was identified on POC use among persons with cirrhosis.
(Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516). DMPA
use has been associated with a higher risk for venous thrombosis
compared with nonuse (Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516). Comment: Hepatic metabolism of exogenous hormones might be impaired in persons with liver dysfunction, which could lead to increased progestin levels in circulation and progestin-related side effects and adverse events (e.g., thrombosis), which might vary by dose and formulation. Any progestin-related hepatotoxicity might be less tolerated in persons with existing liver dysfunction. |
|||
|
Liver
tumors Hepatocellular adenoma and malignant liver tumors are associated with increased risk for adverse health events as a result of pregnancy (Box 3). | |||||||
| a.
Benign | |||||||
| i. Focal
nodular hyperplasia |
2 |
2 |
2 |
Evidence: Limited
evidence suggests that progestin use does not influence either
progression or regression of focal nodular hyperplasia
(Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516). |
|||
| ii.
Hepatocellular adenoma |
2 |
3 |
2 |
Evidence: Limited
evidence suggests that hepatocellular adenomas generally regress
or remain stable during progestin use (Supplementary Appendix,
https://stacks.cdc.gov/view/cdc/156516). |
|||
| b. Malignant
(hepatocellular carcinoma) |
3 |
3 |
3 |
Evidence: No direct
evidence was identified on POC use among persons with
hepatocellular carcinoma (Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516). |
|||
|
Respiratory Conditions
| |||||||
|
Cystic
fibrosis This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 3). |
1 |
2 |
1 |
Clarification: Persons
with cystic fibrosis are at increased risk for diabetes, liver
disease, gallbladder disease, and VTE (particularly related to
use of central venous catheters) and are frequently prescribed
antibiotics. Categories assigned to such conditions in U.S. MEC
should be the same for persons with cystic fibrosis who have
these conditions. For cystic fibrosis, classifications are based
on the assumption that no other conditions are present; these
classifications must be modified in the presence of such
conditions. Clarification: Certain drugs to treat cystic fibrosis (e.g., lumacaftor) might reduce effectiveness of hormonal contraceptives, including oral, injectable, transdermal, and implantable contraceptives. Evidence: Limited evidence suggests that use of COCs or oral contraceptives (type not specified) among women with cystic fibrosis is not associated with worsening of disease severity. Very limited evidence suggests that cystic fibrosis does not impair the effectiveness of hormonal contraception (147). Comment: Persons with cystic fibrosis have a higher prevalence of osteopenia, osteoporosis, and fragility fractures than the general population. Use of DMPA, which has been associated with small changes in BMD, might be of concern. |
|||
|
Hematologic Conditions
| |||||||
|
Thalassemia
|
1 |
1 |
1 |
— |
|||
|
Sickle cell
disease This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 3). |
1 |
2/3 |
1 |
Clarification (DMPA): The
category should be assessed according to the severity of the
condition and risk for thrombosis. Evidence: Limited evidence suggests that POC use does not increase risk for thrombosis among persons with sickle cell disease (Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516). Persons with sickle cell disease are at higher risk for stroke and venous thrombosis than the general population (148–151). Use of DMPA, which has been associated with a higher risk for venous thrombosis compared with nonuse (Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516), might further elevate risk for thrombosis among persons with sickle cell disease. POC might be beneficial in reducing clinical symptoms (e.g., pain crises) (Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516). |
|||
|
Iron deficiency
anemia
|
1 |
1 |
1 |
Comment: Changes in the
menstrual pattern associated with POC use have little effect on
hemoglobin levels. |
|||
|
Solid
Organ Transplantation
| |||||||
|
Solid
organ
transplantation This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 3). | |||||||
| a. No graft
failure |
2 |
2/3 |
2 |
Clarification
(DMPA): DMPA use among persons receiving long-term
immunosuppressive therapy with a history of, or risk factors
for, nontraumatic fractures is classified as category 3.
Otherwise, DMPA use for persons with solid organ transplantation
is classified as category 2. Evidence: One study observed no differences in transplant-related adverse outcomes (e.g., infection, graft failure, and graft rejection) or occurrence of pregnancy between transplant recipients using the implant and those using no hormonal method (Supplementary Appendix, https://stacks.cdc.gov/view/cdc/156516). No direct evidence was identified on bone health or fracture with use of POCs, including DMPA, among persons with solid organ transplantation. Persons with solid organ transplantation have a higher prevalence of osteoporosis and fracture than the general population, especially in the early posttransplantation period (152). Use of DMPA, which has been associated with small changes in bone mineral density compared with nonuse (4) might further elevate risk for fracture among persons with solid organ transplantation. |
|||
| b. Graft failure |
2 |
2/3 |
2 |
||||
|
Drug
Interactions
| |||||||
|
Antiretrovirals used for
prevention (PrEP)
or
treatment of HIV infection
|
Comment: These
recommendations generally are for ARV agents used alone.
However, most persons receiving ARV are using multiple drugs in
combination. In general, whether interactions between ARVs and
hormonal contraceptives differ when ARVs are given alone or in
combination is unknown. |
||||||
| See the
following guidelines for the most up-to-date recommendations on
drug-drug interactions between hormonal contraception and
antiretrovirals: 1) Recommendations for the Use of
Antiretroviral Drugs During Pregnancy and Interventions to
Reduce Perinatal HIV Transmission in the United States
(https://clinicalinfo.hiv.gov/en/guidelines/perinatal/prepregnancy-counseling-childbearing-age-overview?view=full#table-3)
(153) and 2) Guidelines for the Use
of Antiretroviral Agents in Adults and Adolescents with HIV
(https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/drug-interactions-overview?view=full)
(154). | |||||||
| a. Nucleoside
reverse
transcriptase inhibitors
(NRTIs) | |||||||
| i.
Abacavir (ABC) |
1 |
1 |
1 |
Evidence:
NRTIs do not appear to have significant risk for interactions
with hormonal contraceptive methods (155–160). |
|||
| ii.
Tenofovir (TDF) |
1 |
1 |
1 |
||||
| iii.
Zidovudine (AZT) |
1 |
1 |
1 |
||||
| iv.
Lamivudine (3TC) |
1 |
1 |
1 |
||||
| v.
Didanosine (DDI) |
1 |
1 |
1 |
||||
| vi.
Emtricitabine (FTC) |
1 |
1 |
1 |
||||
| vii.
Stavudine (D4T) |
1 |
1 |
1 |
||||
| b.
Nonnucleoside reverse
transcriptase
inhibitors
(NNRTIs) | |||||||
| i.
Efavirenz (EFV) |
2 |
1 |
2 |
Clarification: Evidence
suggests drug interactions between EFV and certain hormonal
contraceptives. These interactions might reduce the
effectiveness of the hormonal
contraceptive. Evidence: One study found that women using etonogestrel implants with EFV had a higher pregnancy rate than women not using ARVs, although confidence intervals overlapped and absolute pregnancy rates were still lower than for other hormonal methods; another study found that etonogestrel levels were decreased and 5% of women had presumptive ovulation while using etonogestrel implants with EFV (161,162). Three studies of women using LNG implants demonstrated increased pregnancy rates for women using EFV-containing ARV therapy compared with no ARV use, although absolute pregnancy rates were still lower than for other hormonal methods in one study (162–164); another study of LNG implant users found no difference in pregnancy rates with EFV compared with no EFV (165). No significant effects were found on pregnancy rates, DMPA levels, EFV levels, or HIV disease progression in women using DMPA and EFV compared with DMPA alone (162,165–169). No significant effects were found on HIV disease progression in women using LNG implants and EFV compared with no ARVs (164). No data have assessed effectiveness of contraceptive implants during later years of use when progestin concentrations are lower and risk for failure from drug interactions might be greater. |
|||
| ii.
Etravirine (ETR) |
1 |
1 |
1 |
— |
|||
| iii.
Nevirapine (NVP) |
1 |
1 |
1 |
Evidence: Five studies
found no significant increase in pregnancy rates among women
using implants and NVP compared with implants alone (162–165,170).
Four studies found no significant increase in pregnancy rates
among women using DMPA or other contraceptive injectables and
NVP compared with DMPA or other contraceptive injectables alone
(162,165,168,171). One
study found no ovulations or changes in DMPA concentrations
(166). No effect was found on HIV
disease progression with use of NVP and DMPA or LNG implants
(164,166,168–170,172). No
data have assessed effectiveness of contraceptive implants
during later years of use when progestin concentrations are
lower and risk for failure from drug interactions might be
greater. |
|||
| iv.
Rilpivirine (RPV) |
1 |
1 |
1 |
— |
|||
| c.
Ritonavir-boosted
protease inhibitors | |||||||
| i.
Ritonavir-boosted atazanavir (ATV/r) |
2 |
1 |
2 |
Clarification:
Theoretically, drug interactions might occur between certain
ritonavir-boosted protease inhibitors and certain hormonal
contraceptives that might reduce the effectiveness of the
hormonal contraceptive. Any potential effect on contraceptive
effectiveness is likely to be lower with DMPA than with other
POCs because of the higher dose of
DMPA. Evidence: One pharmacokinetic study demonstrated increased progestin concentrations with use of POPs and ATV/r compared with POPs alone (173). |
|||
| ii.
Ritonavir-boosted darunavir (DRV/r) |
2 |
1 |
2 |
Clarification:
Theoretically, drug interactions might occur between certain
ritonavir-boosted protease inhibitors and certain hormonal
contraceptives that might reduce the effectiveness of the
hormonal contraceptive. Any potential effect on contraceptive
effectiveness is likely to be lower with DMPA than with other
POCs because of the higher dose of DMPA. |
|||
| iii.
Ritonavir-boosted fosamprenavir (FPV/r) |
2 |
1 |
2 |
Clarification:
Theoretically, drug interactions might occur between certain
ritonavir-boosted protease inhibitors and certain hormonal
contraceptives that might reduce the effectiveness of the
hormonal contraceptive. Any potential effect on contraceptive
effectiveness is likely to be lower with DMPA than with other
POCs because of the higher dose of DMPA. |
|||
| iv.
Ritonavir-boosted lopinavir (LPV/r) |
1 |
1 |
1 |
Evidence: One study
demonstrated no pregnancies, no ovulations, no change in LPV/r
level, and no change in HIV disease progression in women using
DMPA (174); another study found a small
increase in pregnancy rate in women using DMPA with LPV/r
compared with no ARV therapy, however confidence intervals
overlapped (162). Two studies found no
increased risk for pregnancy in women using implants (162,163). Two
studies found contraceptive hormones increased in women using
LPV/r with DMPA or etonogestrel implants (161,174). |
|||
| v.
Ritonavir-boosted saquinavir (SQV/r) |
2 |
1 |
2 |
Clarification:
Theoretically, drug interactions might occur between certain
ritonavir-boosted protease inhibitors and certain hormonal
contraceptives that might reduce the effectiveness of the
hormonal contraceptive. Any potential effect on contraceptive
effectiveness is likely to be lower with DMPA than with other
POCs because of the higher dose of DMPA. |
|||
| vi.
Ritonavir-boosted tipranavir (TPV/r) |
2 |
1 |
2 |
Clarification:
Theoretically, drug interactions might occur between certain
ritonavir-boosted protease inhibitors and certain hormonal
contraceptives that might reduce the effectiveness of the
hormonal contraceptive. Any potential effect on contraceptive
effectiveness is likely to be lower with DMPA than with other
POCs because of the higher dose of DMPA. |
|||
| d. Protease
inhibitors
without ritonavir | |||||||
| i.
Atazanavir (ATV) |
1 |
1 |
1 |
Comment: When ATV is
administered with cobicistat, theoretical concern exists for a
drug interaction with hormonal contraceptives. Cobicistat is an
inhibitor of CYP3A and CYP2D6 and could theoretically increase
contraceptive hormone levels. However, its effects on CYP
enzymes and drug levels might vary when combined with other
ARVs. |
|||
| ii.
Fosamprenavir (FPV) |
2 |
2 |
2 |
Clarification:
Theoretical concern exists that interactions between FPV and
hormonal contraceptives leading to decreased levels of FPV might
diminish effectiveness of the ARV drug. The drug interaction
likely involves CYP3A4 pathways; POCs have less effect on CYP3A4
enzymes than CHCs. |
|||
| iii.
Indinavir (IDV) |
1 |
1 |
1 |
— |
|||
| iv.
Nelfinavir (NFV) |
2 |
1 |
2 |
Clarification:
Theoretically, drug interactions might occur between certain
protease inhibitors and certain hormonal contraceptives that
might reduce the effectiveness of the hormonal contraceptive.
Any potential effect on contraceptive effectiveness is likely to
be lower with DMPA than with other POCs because of the higher
dose of DMPA. Concern exists that interactions between NFV and
POCs might decrease NFV levels. Evidence: One study found no pregnancies, no ovulations, no change in DMPA concentrations and no change in HIV disease progression with use of DMPA and NFV compared with DMPA alone; NFV concentrations were decreased with concomitant DMPA use (166,168). |
|||
| e. CCR5
co-receptor
antagonists | |||||||
| i.
Maraviroc (MVC) |
1 |
1 |
1 |
— |
|||
| f. HIV
integrase strand transfer
inhibitors | |||||||
| i.
Raltegravir (RAL) |
1 |
1 |
1 |
— |
|||
| ii.
Dolutegravir (DTG) |
1 |
1 |
1 |
— |
|||
| iii.
Elvitegravir (EVG) |
1 |
1 |
1 |
Comment: When EVG is
administered with cobicistat, theoretical concern exists for a
drug interaction with hormonal contraceptives. Cobicistat is an
inhibitor of CYP3A and CYP2D6 and could theoretically increase
contraceptive hormone levels. However, its effects on CYP
enzymes and drug levels might vary when combined with other
ARVs. |
|||
| g. Fusion
inhibitors | |||||||
| i.
Enfuvirtide |
1 |
1 |
1 |
— |
|||
|
Anticonvulsant therapy
| |||||||
| a. Certain anticonvulsants
(phenytoin, carbamazepine, barbiturates, primidone, topiramate,
and oxcarbazepine) |
2 |
1 |
3 |
Clarification: Although
the interaction of certain anticonvulsants with POPs and
etonogestrel implants is not harmful, it is likely to reduce the
effectiveness of POPs and etonogestrel implants. Whether
increasing the hormone dose of POPs alleviates this concern
remains unclear. Use of other contraceptives should be
encouraged for persons who are long-term users of any of these
drugs. Use of DMPA is a category 1 because its effectiveness is
not decreased by use of certain
anticonvulsants. Evidence: Use of certain anticonvulsants might decrease the effectiveness of POCs (175–178). |
|||
| b. Lamotrigine |
1 |
1 |
1 |
Evidence: No drug
interactions have been reported among women with epilepsy
receiving lamotrigine and POCs (178,179). |
|||
|
Antimicrobial therapy
| |||||||
| a. Broad-spectrum
antibiotics |
1 |
1 |
1 |
— |
|||
| b. Antifungals |
1 |
1 |
1 |
— |
|||
| c.
Antiparasitics |
1 |
1 |
1 |
— |
|||
| d. Rifampin or rifabutin
therapy |
2 |
1 |
3 |
Clarification: Although
the interaction of rifampin or rifabutin with POPs and
etonogestrel implants is not harmful, it is likely to reduce the
effectiveness of POPs and etonogestrel implants. Use of other
contraceptives should be encouraged for persons who are
long-term users of any of these drugs. Use of DMPA is a category
1 because its effectiveness is not decreased by use of rifampin
or rifabutin. Whether increasing the hormone dose of POPs
alleviates this concern remains unclear. |
|||
|
Psychotropic medications
|
Comment: For many common
psychotropic agents, limited or no theoretical concern exits for
clinically significant drug interactions when co-administered
with hormonal contraceptives. However, either no or very limited
data exist examining potential interactions for these classes of
medications. |
||||||
| a. Selective serotonin
reuptake inhibitors (SSRIs) |
1 |
1 |
1 |
Evidence: No evidence
specifically examined the use of POCs with SSRIs. Limited
clinical and pharmacokinetic data do not demonstrate concern for
SSRIs decreasing the effectiveness of oral contraceptives.
Limited evidence suggests that for women taking SSRIs, the use
of hormonal contraceptives was not associated with differences
in effectiveness of the SSRI for treatment or in adverse events
when compared with women not taking hormonal contraceptives
(180). Comment: Drugs that are inhibitors of CYP3A4 or CYP2C9 theoretically have the potential to increase levels of contraceptive steroid, which might increase adverse events. Fluvoxamine is an SSRI known to be a moderate inhibitor of both 3A4 and 2C9; however, no clinical or pharmacokinetic studies were identified to explore potential drug-drug interactions. |
|||
| St. John’s wort | 2 |
1 |
2 |
Evidence: No evidence
specifically examined the use of POCs with St. John’s
wort. Although clinical data are limited, studies with
pharmacokinetic and pharmacodynamics outcomes raise concern that
St. John’s wort might decrease effectiveness of hormonal
contraceptives, including increased risk for breakthrough
bleeding and ovulation and increased metabolism of estrogen and
progestin. Any interactions might be dependent on the dose of
St. John’s wort, and the concentration of active
ingredients across types of St. John’s wort preparations
might vary (181). Comment: Any potential effect on contraceptive effectiveness is likely to be lower with DMPA than with other POCs because of the higher dose of DMPA. |
|||
Abbreviations: ARV = antiretroviral; BMD = bone mineral density; BMI = body mass index; CHC = combined hormonal contraceptive; CKD = chronic kidney disease; COC = combined oral contraceptive; Cu-IUD = copper intrauterine device; CYP = cytochrome P450; DMPA = depot medroxyprogesterone acetate; DRSP = drospirenone; DVT = deep venous thrombosis; hCG = human chorionic gonadotropin; HDL = high-density lipoprotein; IBD = inflammatory bowel disease; IM = intramuscular; LDL = low-density lipoprotein; LNG = levonorgestrel; LNG-IUD = levonorgestrel intrauterine device; NA = not applicable; PE = pulmonary embolism; PID = pelvic inflammatory disease; POC = progestin-only contraceptive; POP = progestin-only pill; PrEP = pre-exposure prophylaxis; RCT = randomized clinical trial; SLE = systemic lupus erythematosus; STI = sexually transmitted infection; U.S. MEC = U.S. Medical Eligibility Criteria for Contraceptive Use; U.S. SPR = U.S. Selected Practice Recommendations for Contraceptive Use; VTE = venous thromboembolism.