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DOI: 10.1055/a-1259-1609
Hormonal Contraception. Guideline of the DGGG, OEGGG and SGGG (S3 Level, AWMF Registry Number 015/015, January 2020)
Article in several languages: English | deutsch
- Abstract
- I Guideline Information
- II Guideline Application
- III Methodology
- IV Guideline
- 2 Arterial Thromboembolic Events (ATE)
- References/Literatur
Abstract
Aims This is an official interdisciplinary guideline published and coordinated by the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (OEGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The guideline was developed for use in German-speaking regions and is backed by numerous professional societies and organizations. The aim of this guideline is to provide an evidence- and consensus-based overview of the diagnostic approach and the management of hormonal contraception based on a systematic evaluation of the relevant literature.
Methods To compile this S3-guideline, a systematic search for evidence was carried out in PubMed and the Cochrane Library to adapt existing guidelines and identify relevant reviews and meta-analyses. A structured evaluation of the evidence was subsequently carried out on behalf of the Guidelines Commission of the DGGG, and a structured consensus was achieved based on consensus conferences attended by representative members from the different specialist societies and professions.
Recommendations Evidence-based recommendations about the advice given to women requesting contraception were compiled. The guideline particularly focuses on prescribing contraceptives which are appropriate to womenʼs individual needs, take account of her personal circumstances, and have few or no side effects.
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I Guideline Information
Guidelines program of the DGGG, OEGGG and SGGG
For information on the guidelines program, please refer to the end of this guideline.
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Citation format
Hormonal Contraception. Guideline of the DGGG, OEGGG and SGGG (S3 Level, AWMF Registry Number 015/015, January 2020). Geburtsh Frauenheilk 2021; 81: 152 – 182
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Guideline documents
The complete long version and a planned slide version of this guideline as well as a list of the conflicts of interest of all authors are available in German on the homepage of the AWMF: http://www.awmf.org/leitlinien/detail/ll/015-015.html
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Guideline authors
|
Author |
AWMF professional society |
|---|---|
|
Prof. Dr. med. Petra Stute |
Swiss Society for Gynecology and Obstetrics [Schweizerische Gesellschaft für Gynäkologie und Geburtshilfe] (SGGG) Quality Assurance Commission [Kommission Qualitätssicherung] (QSK) German Menopause Society [Deutsche Menopause Gesellschaft e. V.] (DMG) |
|
Prof. Dr. med. Ludwig Kiesel |
Germany Society for Gynecology and Obstetrics [Deutsche Gesellschaft für Gynäkologie und Geburtshilfe] (DGGG) |
|
Author Mandate holder |
DGGG working group/AWMF/non-AWMF professional society/organization/association |
|---|---|
|
* control |
|
|
Prof. Dr. med. Rupert Bauersachs |
Expert, member of the steering committee |
|
Prof. Dr. med. Jan Beyer-Westendorf |
German Society for Angiology/Vascular Medicine [Deutsche Gesellschaft für Angiologie – Gesellschaft für Gefäßmedizin e. V.] (DGA) |
|
PD Dr. med. Tina Buchholz |
German Society for Reproductive Medicine [Deutsche Gesellschaft für Reproduktionsmedizin] |
|
Prof. Dr. med. Kai Bühling |
German Society for Womenʼs Health [Deutsche Gesellschaft für Frauengesundheit e. V.] (DGF), member of the steering committee |
|
Prof. Dr. med. Hans-Christoph Diener |
German Society for Neurology [Deutsche Gesellschaft für Neurologie] (DGN) |
|
Anke Erath |
Federal Center for Health Education [Bundeszentrale für gesundheitliche Aufklärung] (BZgA) |
|
Dr. med. Ronald Fischer |
Society for Thrombosis and Hemostasis Research [Gesellschaft für Thrombose- und Hämostaseforschung] (GTH) |
|
PD Dr. med. Stefanie Förderreuther |
German Migraine and Headache Society [Deutsche Migräne- und Kopfschmerzgesellschaft] (DMKG) |
|
PD Dr. med. Heiko B. G. Franz |
Medical Law Task Force of the DGGG [Arbeitsgemeinschaft Medizinrecht der DGGG]* |
|
Claudia Halstrick |
Rechtsanwältin BVF |
|
Prof. Dr. med. Viola Hach-Wunderle |
German Society of Phlebology [Deutsche Gesellschaft für Phlebologie] (DGP) |
|
Prof. Dr. med. Peymann Hadji |
Osteology Umbrella Association [Dachverband Osteologie] (DVO) |
|
Sanitätsrat Dr. med. Werner Harlfinger |
Professional Association of Gynecologists [Berufsverband für Frauenärzte] (BVF) |
|
Dr. med. Cornelia Jaursch-Hancke |
German Society for Internal Medicine [Deutsche Gesellschaft für Innere Medizin e. V.] (DGIM) |
|
Prof. Dr. med. Ludwig Kiesel |
German Society for Endocrinology [Deutsche Gesellschaft für Endokrinologie], member of the steering committee |
|
Dr. med. Klaus König |
Professional Association of Gynecologists (BVF), member of the steering committee |
|
Dr. med. Günter Krämer |
German Society for Epileptology [Deutsche Gesellschaft für Epileptologie e. V.] |
|
PD Dr. med. Gert Naumann |
Study Group for Urogynecology and Plastic Pelvic Floor Reconstruction [Arbeitsgemeinschaft für Urogynäkologie und plastische Beckenbodenrekonstruktion e. V.] (AGUB) of the DGGG |
|
PD Dr. med. Patricia G. Oppelt |
Working Group for Pediatric and Adolescent Gynecology [Arbeitsgemeinschaft Kinder- und Jugendgynäkologie e. V.], member of the steering committee |
|
Dr. med. Jutta Pliefke |
pro familia German Society for Family Planning, Sexual Education and Counseling [pro Familia Deutsche Gesellschaft für Familienplanung, Sexualpädagogik und Sexualberatung e. V. |
|
PD Dr. med. Stefan Rimbach |
Gynecological Endoscopy Working Group of the DGGG [Arbeitsgemeinschaft Gynäkologische Endoskopie (AGE) e. V. der DGGG] |
|
Dr. med. Hannelore Rott |
Professional Association of German Hemostaseologists [Berufsverband der Deutschen Hämostaseologen] (BDDH) |
|
Eckhard Schroll |
Federal Center for Health Education (BZgA) |
|
Dr. med. Claudia Schumann |
German Society of Psychosomatic Gynecology and Obstetrics [Deutsche Gesellschaft für Psychosomatische Frauenheilkunde und Geburtshilfe e. V.] (DGPFG) |
|
Dr. med. Helga Seyler |
Working Group on Womenʼs Health in Medicine, Psychotherapy and Society [Arbeitskreis Frauengesundheit in Medizin, Psychotherapie und Gesellschaft e. V.] |
|
Prof. Dr. med. Petra Stute |
Swiss Society for Gynecology and Obstetrics (SGGG) Quality Assurance Commission (QSK) German Menopause Society (DMG) |
|
Prof. Dr. med. Clemens Tempfer |
Working Group for Gynecologic Oncology of the DKG [Arbeitsgemeinschaft für gynäkologische Onkologie der DKG], AGO |
|
Dr. med. Ines Thonke, M. Sc. |
National Women and Health Network [Nationales Netzwerk Frauen und Gesundheit] |
|
Prof. Dr. med. Bettina Toth |
German Society for Gynecological Endocrinology and Reproductive Medicine [Deutsche Gesellschaft für gynäkologische Endokrinologie und Fortpflanzungsmedizin e. V.], member of the steering committee |
|
Prof. Dr. med. Ludwig Wildt |
Austrian Society for Gynecology and Obstetrics [Österreichische Gesellschaft für Gynäkologie und Geburtshilfe e. V.] (OEGGG) |
|
PD Dr. med. Rainer Zotz |
German Society for Angiology/Vascular Medicine (DGA); consulted as a specialist with regard to Chapter 1.6 (only one DGA representative had the right to vote if a vote was taken) |
|
PD Dr. med. Sabine Segerer |
Expert, member of the steering committee |
|
Prof. Dr. med. Joseph Neulen |
Expert, member of the steering committee |
|
Sebastian Franik |
Expert, member of the steering committee |
The guidelines were moderated by Dr. med. Monika Nothacker (AWMF-certified guideline moderator).
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Abbreviations
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II Guideline Application
Purpose and objectives
The aim of the guideline is to create an evidence-based list of recommendations which can be used when advising women who require contraception along with an evidence-based list of recommendations for prescribing appropriate contraceptives which are suited to womenʼs individual needs, take account of womenʼs personal circumstances and risk profiles, and have few or no side effects.
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Targeted areas of patient care
Outpatient care and primary and specialist medical care.
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Target user groups/target audience
The recommendations of this guideline are aimed at gynecologists, general practitioners, pediatricians, neurologists, and specialists working the fields of phlebology, angiology, osteology, internal medicine, epileptology, hemostaseology and migraines, as well as members from other professional groups involved in the care of patients who take hormonal contraceptives. Target patient group: women of reproductive age.
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Adoption and period of validity
The validity of this guideline was confirmed by the executive boards/heads of the participating medical professional societies, working groups, organizations and associations as well as by the boards of the DGGG, SGGG, OEGGG and the DGGG/OEGGG/SGGG Guidelines Commission in December 2018, March 2019 and again after implementing the suggestions proposed for the draft version sent out for consultation in August 2019, and was thus approved in its entirety. This guideline is valid from 1st August 2019 through to 31st July 2024. Because of the contents of this guideline, this period of validity is only an estimate. If changes are urgently required, the guideline may be updated earlier; similarly, if the guideline continues to reflect the current state of knowledge, then its period of validity can be extended.
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III Methodology
Basic principles
The method used to prepare this guideline was determined by the class to which this guideline was assigned. The AWMF Guidance Manual (version 1.0) has set out the respective rules and requirements for different classes of guidelines. Guidelines are differentiated into lowest (S1), intermediate (S2), and highest (S3) class. The lowest class is defined as consisting of a set of recommendations for action compiled by a non-representative group of experts. In 2004, the S2 class was divided into two subclasses: a systematic evidence-based subclass (S2e) and a structural consensus-based subclass (S2k). The highest S3 class combines both approaches.
This guideline has been classified as: S3
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Grading of evidence based on SIGN
To assess the evidence (levels 1 – 4) of additionally selected primary studies, this guideline used the classification system of the Scottish Intercollegiate Guidelines Network (SIGN) in its most recent version from 2011 ([Table 3]).
|
Level |
Description |
|---|---|
|
Source: http://www.sign.ac.uk/pdf/sign50.pdf Source (contents, abbreviations, notes): http://www.cebm.net/?o=1025 |
|
|
1++ |
High-quality meta-analyses, systematic reviews of RCTs, or RCTs with a very low risk of bias |
|
1+ |
Well-conducted meta-analyses, systematic reviews, or RCTs with a low risk of bias |
|
1− |
Meta-analyses, systematic reviews, or RCTs with a high risk of bias |
|
2++ |
High-quality systematic reviews of case-control or cohort studies, or high-quality case-control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal |
|
2+ |
Well-conducted case-control studies or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal |
|
2− |
Case-control studies or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal |
|
3 |
Non-analytic studies, e.g. case reports, case series |
|
4 |
Expert opinion |
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Grading of recommendations
The grading of evidence in an S3-guideline using a level-of-evidence system also allows the strength of the recommendations made in the guideline to be graded. The degree of recommendation is differentiated into three levels, and the different strengths of recommendation are indicated by the respective semantic choice of words. This commonly used grading of recommendations is not just used by the AWMF but also by the German Medical Association in its National Guidelines on Care (Nationale Versorgungsleitlinien, NVL). The wording chosen to indicate the strength of the recommendation should be explained in the background text.
In this context, the terms “grade”ʼ, “level” and “strength” indicate the degree of certainty about issuing a recommendation after weighing up the benefits and the harm but are not an indication of whether the recommendation itself is binding. Guidelines are recommendatory, i.e., non-binding.
Individual Statements and Recommendations are not differentiated by symbols but by syntax alone ([Table 4]):
|
Symbol |
Description |
Syntax |
|---|---|---|
|
A |
strong recommendation |
must/must not |
|
B |
simple recommendation |
should/should not |
|
0 |
open recommendation, not very authoritative |
may/may not |
The above-described differentiation of Recommendations reflects both the assessment of the evidence and the clinical relevance of the studies on which the evidence is based and incorporates factors in the studies which are not included in the grading of evidence, such as the choice of patient cohort, intention-to-treat or outcome analyses, medical actions and ethical behavior towards the patient, country-specific applicability, etc. In contrast, a strong, moderate or poor strength of evidence can result in a strong, simple or open recommendation. Only if the strength of evidence is moderate, can the recommendation be either upgraded or downgraded to a Grade A or Grade 0 recommendation. In exceptional cases, a limited/open recommendation coupled with the highest level of evidence will need to be explained in the background text.
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Strong evidence → Grade A or Grade B recommendation
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Moderate evidence → Grade A or Grade B or Grade 0 recommendation
-
Weak evidence → Grade B or Grade 0 recommendation
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Statements
If professional statements are included in this guideline not as recommendations for action but as a simple presentation of facts, then they are referred to as “Statements”. It is not possible to provide information about the level of evidence for Statements.
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Achieving consensus and strength of consensus
As part of the structured approach for reaching a consensus, participants attended sessions where those entitled to vote took a vote on preformulated Statements and Recommendations. Four consensus conferences were held in total. Recommendations were discussed and adopted at the conferences. The formal consensus building process was moderated by Dr. med. Monika Nothacker, who has a AWMF qualification on moderating consensus building procedures. The consensus conference used a nominal group method. At the start of the conference, proposed recommendations and their respective levels of evidence were presented by the respective experts who had prepared the presentations. The recommendations and their evidence were then discussed. This was followed by an opportunity to ask questions about the contents/clarify contentious issues. The draft recommendations were summarized in brief documents which were commented on by every member of the group; diverging suggestions were duly noted. The next step consisted of an initial vote and, if no consensus could be reached, further debates/discussions, followed by a final vote. A consensus (> 75%) or strong consensus (> 95%) was reached for all Recommendations ([Table 5]).
|
Symbol |
Level of consensus |
Extent of agreement in percent |
|---|---|---|
|
+++ |
Strong consensus |
> 95% of participants agree |
|
++ |
Consensus |
> 75 – 95% of participants agree |
|
+ |
Majority agreement |
> 50 – 75% of participants agree |
|
– |
No consensus |
< 51% of participants agree |
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Expert consensus
An expert consensus was established if no scientific evidence for specific Recommendations/Statements was found. The term “expert consensus” (EC) used here is synonymous with terms used in other guidelines such as “good clinical practice” (GCP) or “clinical consensus point” (CCP). The strength of the recommendation is graded in the same way as described in the chapter “Grading of recommendations” but is only expressed semantically (“must”/“must not” or “should”/“should not” or “may”/“may not”) without using symbols.
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IV Guideline
1 Venous thromboembolic events
1.1 Impact of hormonal contraceptives on the risk of venous thromboembolism
Even though the overall risk of venous thromboembolism (VTE) (especially deep vein thrombosis [DVT] of the leg, arm vein thrombosis, cerebral venous thrombosis and pulmonary embolism [PE]) in women of childbearing age is low (around 5/10 000 per year), the risk of VTE is higher when women take combined hormonal contraceptives (CHC). The increased risk depends on the concentration and percentage of estrogen and the percentage and type of progestogen (about 2 to 4 times higher) used in the preparation. The risk of VTE is also higher during pregnancy (about 6 times higher during pregnancy and about 22 times higher during puerperium). It is therefore important to consider every patientʼs individual risk of VTE when advising her about the most suitable method of contraception ([Table 6]).
|
Progestogen in COC |
Relative risk of VTE compared to COC with levonorgestrel |
Incidence (per 10 000 women per year of use) |
Estimated number of new cases of VTE in Germany per year (around 6.8 million users) (15) |
|---|---|---|---|
|
Non-users |
– |
2 |
1360 |
|
Levonorgestrel |
1 |
5 – 7 |
3400 – 4760 |
|
Norgestimate/norethisterone |
1 |
5 – 7 |
3400 – 4760 |
|
Dienogest |
1.6 |
8 – 11 |
5440 – 7480 |
|
Gestodene/desogestrel/drospirenone |
1.5 – 2 |
9 – 12 |
6120 – 8160 |
|
Etonogestrel/norelgestromin |
1 – 2 |
6 – 12 |
4080 – 8160 |
|
Chlormadinone/nomogestrol acetate + E2 |
unknown |
unknown |
unknown |
Every patient must be asked detailed questions about her prior medical history, and all potential VTE risk factors must be identified to assess her individual risk of VTE when newly prescribing hormonal contraceptives. The minimum information about the patient that must be collected is:
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age
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body mass index (BMI)
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smoking status (including moderate consumption of cigarettes per day)
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existing or foreseeable immobility or planned major surgery
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previous history of VTE (including potential triggers to identify hormone-related and unprovoked events)
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familial history of VTE (particularly relevant if they are first-degree relatives; the patient must be asked about the age at the time of the VTE, the type of VTE, and potential triggers of VTE, to identify hormone-related and unprovoked events)
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known thrombophilia factors in her family
Once these data have been collected, an initial assessment of the patientʼs overall risk of VTE can be made, based on [Table 7] (adapted from the Faculty of Sexual and Reproductive Healthcare UK Medical Eligibility Criteria for Contraceptive Use [MEC] 2016).
|
Risk factor for VTE |
Relevance for VTE risk when taking hormonal contraceptives |
Recommended actions |
|---|---|---|
|
# According to the 2015 World Health Organization (WHO) guideline, patients with no thrombophilia but with a positive familial history of thrombophilia may take COC. |
||
|
Age > 35 years |
low – moderate |
Provide extensive advice about risks; in principle, all forms of contraception are possible |
|
BMI > 35 kg/m2 |
low – moderate |
Provide extensive advice about risks; taking COC should be avoided if possible |
|
Smoking (cigarettes) |
low – moderate |
Provide extensive advice about risks; taking COC should be avoided if possible (particularly if older than 35 years and/or smoking > 15 cig./day) |
|
≥ 2 of the risk factors listed below
|
moderate – high |
Provide extensive advice about risks; taking COC should be avoided if possible |
|
Prolonged immobility, major surgical procedure |
moderate – high |
Provide extensive advice about risks; patient should not be started on COC; consistent thrombosis prophylaxis prescribed for COC users |
|
Patient has previous history of VTE |
moderate (triggered VTE) to high (unprovoked or hormone-related VTE) |
Taking COC should be avoided; consider consulting a hemostaseology specialist (if consulted, the specialist should test for thrombophilia) |
|
Familial history positive for VTE, with VTE occurring in first-degree relatives below the age of 45 |
moderate (triggered VTE) to high (idiopathic or hormone-related VTE) |
Taking COC# should be avoided; consider consulting a hemostaseology specialist (if consulted, the specialist should test for thrombophilia) |
|
Familial history positive for VTE, with VTE occurring in first-degree relatives above the age of 45 |
low – moderate |
Provide extensive advice about risks; taking COC is possible# if no suitable alternatives are available |
|
Asymptomatic thrombophilia or thrombophilia reported in first-degree relatives |
low – high depending on the type of thrombophilia and its manifestation in the family |
Testing for thrombophilia is indicated and critically important for asymptomatic patients; if thrombophilia is proven, consult with a hemostaseology specialist before starting hormonal contraception |
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1.2 Impact of hormonal contraceptives on the risk of VTE
Combined hormonal contraceptives significantly increase the risk of VTE. This also very much applies to parenteral applications (vaginal ring, contraceptive patches). With the exception of the 3-month contraceptive injection (DMPA), progestogen-only drugs are not associated with an increased risk of VTE.
Each womanʼs individual risk of VTE must be determined before she is prescribed combined contraceptives. If she has an increased risk of VTE, she must not take combined contraceptives.
Women with an increased risk of VTE may take progestogen-only preparations (with the exception of DMPA).
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1.3 Importance of the percentage of progestogen in combined hormonal contraceptives on the risk of VTE
The percentage of progestogen in combined hormonal contraceptives (COC) affects the risk of venous thromboembolism. Progestogen-only drugs are not associated with an increased risk of VTE (with the exception of DMPA).
When prescribing COC, preference should be given to 2nd generation preparations after carefully questioning the patient about her previous medical history of venous thromboembolism (VTE) and her familial history of (VTE). This is particularly important for first-time users of COCs.
In special clinical situations, the patient may be prescribed another COC – after her individual risk has been assessed and she has been informed about the associated increased risk of VTE.
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1.4 Association between hormonal contraceptives and recurrent VTE
Women who currently have or previously had VTE must be advised against continuing to use combined hormonal contraceptives unless they are taking anticoagulant medication to protect against recurrent VTE.
As regards systemic progestogen-only preparations (with the exception of DMPA/NET preparations) and the LNG-IUS, the benefits of effective contraception outweigh the potential VTE risks.
A prior history of VTE is no contraindication for LNG-IUS or a copper IUD.
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1.5 Association between hormonal contraceptives and recurrent VTE despite anticoagulant therapy
An effective form of contraception to prevent unplanned pregnancy and its associated risks (e.g. thromboembolism, embryopathy) is required during anticoagulant therapy.
At the start of anticoagulant therapy, the patient must be advised about safe forms of contraception. Progestogen-only contraception should be the first-line approach, as it can be continued without any problems after anticoagulant therapy has ended. Taking a COC while undergoing anticoagulant treatment is possible, but it is primarily used to prevent and treat abnormal uterine bleeding/ovulation bleeding.
If the risks and benefits have been weighed up and discussed with the patient and a decision has been taken together with the patient to opt for contraception with COC, then the preferred option, based on the currently available data, should be a 2nd generation progestogen COC (e.g. levonorgestrel, norgestimate, norethisterone) and a low percentage of estrogen, as these combinations are associated with the lowest increase in the risk of VTE.
There is currently no prospective evidence that all forms of hormonal contraception increase the risk of recurrent venous thromboembolism in women receiving anticoagulant treatment after prior VTE as long as anticoagulant treatment is continued. A post-hoc analysis showed no increased risk.
As the expected benefits of hormonal contraception (effective contraception; reduction of vaginal bleeding complications during anticoagulant treatment) outweigh the (not yet proven) risk, the patient should continue with her existing hormonal contraception for the duration of anticoagulant treatment, irrespective what type of hormonal contraception it is.
Patients with acute VTE may continue with estrogen-free hormonal contraception even after anticoagulant treatment has been discontinued; patients with acute VTE taking an estrogen-containing contraceptive must switch to estrogen-free contraception at the very latest 6 weeks before discontinuing anticoagulant treatment.
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1.6 Importance of predisposing factors for the risk of VTE
There is no consistent evidence that hypertension, hyperlipidemia, obesity and smoking combined with COC or progestogen-only preparations is associated with a relevant increased risk of venous thrombosis. However, the number of studies is limited.
Hypertension, hyperlipidemia, obesity and smoking are cardiovascular risk factors which should be considered when prescribing COCs or progestogen-only preparations and appropriate measures should be taken to optimize these comorbidities if possible. COCs or progestogen-only preparations are not contraindicated because of a risk of venous thromboembolism in women with these comorbidities. See Chapter 2 on the risk of arterial thromboembolic events.
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2 Arterial Thromboembolic Events (ATE)
2.1 Importance of predisposing factors for the risk of ATE
Combined hormonal contraceptives increase the risk of ischemic cerebral infarction and myocardial infarction.
Different risk factors such as hypertension, smoking, hyperlipidemia increase the risk of ischemic cerebral infarction and myocardial infarction.
Women with hypertension (systolic blood pressure [BP] ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg) should not take estrogen-containing contraceptives.
Women taking combined hormonal contraceptives should have their blood pressure measured at regular intervals (e. g. every 6 months if the woman has no existing risk of ATE; for women with borderline values, the interval should depend on the respective prescribing physician).
Arterial thromboembolic events are correlated with the dose of ethinyl estradiol: the preferred option should therefore be a preparation with the lowest possible estrogen dose.
The relative risk of myocardial infarction for women taking combined oral contraceptives is 1.6 (95% CI: 1.3 – 1.9), the relative risk of cerebral infarction is 1.7 (95% CI: 1.5 – 1.9).
Oral progestogen-only preparations (POP) do not appear to increase the risk of arterial thromboembolism.
Caution should be used when prescribing a 3-month DMPA injectable to women with cardiovascular risk factors, as high-dose progestogens can have a negative impact on serum lipid levels.
Oral and selected non-oral progestogen-only preparations (implant or LNG-IUS) may be prescribed to women with cardiovascular risks.
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2.2 Impact of hormonal contraceptives on the stroke risk of women who suffer from migraine with aura
Women who suffer from migraine with aura must not be prescribed combined hormonal contraceptives. If a woman suffers a migraine with aura while taking combined hormonal contraceptives, she must stop taking this type of contraceptive.
Migraine with aura increases the risk of ischemic cerebral infarction. The elevated risk of ischemic cerebral infarction in women suffering from migraine with aura is even higher if they take hormonal contraceptives.
Women suffering from migraine with or without aura but who do not have additional risk factors for ATE may be prescribed progestogen-only contraceptives. If new onset of migraine with aura occurs in a patient taking a progestogen-only contraception, the patient must stop taking this type of contraception.
Migraine patients may safely use currently available emergency contraception drugs if they need to.
#
2.3 Impact of hormonal contraceptives on the treatment of ovarian cysts
Treatment with combined hormonal contraceptives does not hasten the regression of functional ovarian cysts. This is the case both for spontaneously occurring ovarian cysts and for ovarian cysts which developed after ovarian stimulation.
Combined oral contraceptives must not be used to treat ovarian cysts.
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2.4 Effect of taking hormonal contraceptives when breastfeeding
There is currently not enough data to make a definitive statement about the effect of hormonal contraceptives on the quality and quantity of breast milk.
There is currently not enough data to make a definitive statement about the effect of combined hormonal contraceptives on infant growth rates.
Progestogen-only contraceptives have no negative effects on the volume and quality of milk produced by breastfeeding women.
Progestogen-only contraceptives have no impact on the growth of breastfed infants.
Breastfeeding women should not take combined hormonal contraceptives in the first six months post partum.
Breastfeeding women may take progestogen-only contraceptives for birth control.
The use of combined hormonal contraceptives may be considered for breastfeeding women from six months post partum.
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2.5 Benefits and risks of starting hormonal contraceptives outside the menstrual cycle
The contraceptive efficacy and side-effects profile of quick-start contraception are comparable with those reported for hormonal contraceptives started on the first day of menstruation. Initial better adherence is no longer detectable after about 4 cycles.
Quick-start contraception may be recommended to women who want to start taking hormonal contraceptives.
An additional barrier contraception method must be used in the first week of quick starting contraception.
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3 Additional Effects
3.1 Impact of hormonal contraceptives on hirsutism
COCs, particularly those with an antiandrogenic progestogen component (CPA, CMA, DRSP, DNG), may have a clinically beneficial effect on hirsutism. It is not clear whether the beneficial effect of different antiandrogenic progestogens on hirsutism varies between different preparations.
After extensive counselling and due consideration of the extent of hirsutism and the patientʼs level of psychological stress, treatment with a combined hormonal contraceptive containing an antiandrogenic progestogen component may be recommended.
Patients must be informed about the potential risks of treatment associated with using combined hormonal contraceptives with an antiandrogenic progestogen component and must be informed about alternative treatment methods.
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3.2 Impact of hormonal contraceptives on body weight
No significant increase in body weight was observed in women taking combined hormonal contraceptives. An increase in body weight depending on the duration of use was observed in women using DMPA.
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3.3 Impact of hormonal contraceptives on the risk of developing cardiovascular disease in women with type I and II diabetes mellitus
Combined hormonal contraceptives may be prescribed to women with diabetes (type I and type II) if secondary vascular damage has been excluded. Additional risks such as hypertension or smoking are a contraindication to using combined hormonal contraceptives.
The benefits of combined hormonal contraceptives outweigh the risks for women with diabetes (type I and type II) below the age of 35 years who have no other comorbidities (e.g. hypertension, vascular damage, smoking).
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3.4 Impact of hormonal contraceptives on the risk of hepatic adenoma
Combined hormonal contraceptives can be used safely by patients with focal nodular hyperplasia.
The use of combined hormonal contraceptives is an unacceptable health risk for patients with hepatocellular adenoma or malignant hepatic tumor.
Progestogen-only contraceptives can be used safely by patients with focal nodular hyperplasia.
The use of progestogen-only contraceptives is an unacceptable health risk for patients with hepatocellular adenoma or malignant hepatic tumor.
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3.5 Differences in the benefit-risk profile of extended cycle hormonal contraceptives
The contraceptive efficacy of combined hormonal contraceptives is the same, irrespective of whether dosing is conventional (i.e., includes a monthly 7-day break) or continuous. There are no indications that there are any differences in health risks between the two types. Menstruation-related symptoms are lower with extended cycle oral contraceptives compared to conventional COCs.
Extended-cycle combined hormonal contraceptives are superior to conventional combined hormonal contraceptives with regard to menstrual symptoms (dysmenorrhea, catamenial migraine, intestinal irritation and days of menstruation).
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4 Efficacy
4.1 Impact of obesity on the Pearl Index
There is no evidence that the contraceptive efficacy of hormonal contraceptives is lower in obese women. However, the data for grade II (BMI 35.0 – 39.9 kg/m²) and III (BMI ≥ 40 kg/m²) obesity are contradictory. The efficacy of a combined hormonal patch could be lower in women with a higher body weight.
Women with grade II (BMI 35.0 – 39.9 kg/m²) or III (BMI ≥ 40 kg/m²) obesity should be offered an IUD or another non-hormonal contraceptive method.
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4.2 Effect of obesity on the efficacy of emergency hormonal contraception
There are some indications that the contraceptive efficacy of emergency hormonal contraceptives, particularly the efficacy of LNG-containing emergency contraceptives, is lower in obese women.
Obese women requiring emergency contraception should be informed about the efficacy of all available options, including the efficacy of copper IUDs. A copper IUD is the most effective form of emergency contraception, irrespective of body weight. A copper IUD should be recommended as emergency contraception for women with a BMI ≥ 30 kg/m².
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4.3 Difference in the efficacy of UPA and LNG
LNG and UPA are effective contraceptive drugs for emergency hormonal contraception.
Emergency hormonal contraceptives must be taken as early as possible after unprotected sexual intercourse.
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4.4 Impact of continued hormonal contraception on the efficacy of emergency contraception
Hormonal contraception may be started together with back-up contraception (e.g. additional barrier method/abstinence for the next seven days) on the same day or on the day after taking LNG. Hormonal contraception may be started five days after taking UPA. In the meantime, women must either use back-up contraception or be abstinent.
Women who take emergency hormonal contraceptives should be advised about subsequent forms of contraception and be provided with them, if necessary.
Hormonal contraceptives should be started within 24 hours after taking LNG. Additional back-up contraception (e. g. an additional barrier method) must be used over the next seven days or women must be abstinent for seven days after taking LNG.
Women who take UPA for emergency contraception should start taking hormonal contraceptives five days after taking UPA. Back-up contraception (e. g. an additional barrier method) must be used or women must be abstinent during these five days and for 14 days after starting hormonal contraception.
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4.5 Impact of hormonal contraceptives on dysmenorrhea
The use of hormonal oral contraceptives may help to reduce dysmenorrhea.
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4.6 Benefit of hormonal contraceptives for the treatment of hypermenorrhea
The use of hormonal oral contraceptives may help to reduce hypermenorrhea.
Women should be informed that the levonorgestrel-releasing intrauterine system (LNG-IUS) may offer effective treatment for hypermenorrhea. However, other pathologies should first be excluded.
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5 Bones/Psyche
5.1 Effect of hormonal contraceptives on premenstrual syndrome
There is no evidence that cyclical intake of combined hormonal contraceptives or progestogen-only contraceptives has an impact on PMS. However, extended-cycle combined hormonal contraceptives may alleviate symptoms. Drospirenone-containing oral contraceptives may reduce symptoms of PMDD. However, there is also evidence of a significant placebo effect. It is currently not clear whether the effect persists even after three months of treatment.
The use of extended-cycle combined oral contraceptives to treat PMS and the use of a combined drospirenone-containing contraceptive to treat PMDD may be considered after weighing up the individual risk (thrombosis).
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5.2 Impact of COC on the fracture rate
There is no evidence that COC affects the fracture risk.
However, only cohort and case-control studies are currently available, and there are no RCTs with sufficiently long observation periods. An increased risk of fracture was only observed in specific subgroups.
It is not possible to give a definitive answer at present to the question whether taking a COC prior to reaching peak bone mass (PBM) has an unfavorable impact on fracture risk.
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5.3 Impact of DMPA on the fracture rate
DMPA use increases the lifetime risk of fracture depending on the duration of use.
However, only cohort and case-control studies are currently available, and there are no RCTs with sufficiently long observation periods.
It is not possible to give a definitive answer at present to the question whether DMPA use prior to reaching peak bone mass (PBM) has a particularly unfavorable impact on the future risk of fracture.
DMPA should not be recommended as a first-choice contraceptive. DMPA should be used for as short a period as possible.
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5.4 Impact of hormonal contraceptives on bone density, bone fractures and bone markers in women with anorexia nervosa
The primary goal of increasing bone density in patients with anorexia nervosa is achieved by treating the underlying disease, accompanied by an increase in weight and/or restoration of menstruation. Studies carried out to date found no positive effect of using combined hormonal contraceptives on bone density.
Patients with anorexia nervosa should not be prescribed combined hormonal contraceptives to increase bone density.
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5.5 Association between hormonal contraceptive use and risk of depression
Taking hormonal contraceptives may result in mood swings.
Women who take hormonal contraceptives should be informed about the possible occurrence of mood swings.
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5.6 Impact of hormonal contraceptives on pre-existing depression
Taking hormonal contraceptives does not lead to worsening of pre-existing depression. Some studies have reported an improvement in depressive symptoms when taking COCs.
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5.7 Impact of hormonal contraceptives on libido
Hormonal contraceptives may – in addition to many other factors – have an impact on female sexuality and libido in terms of an increase or decrease. Study results indicate that the majority of women do not notice any changes.
Hormonal contraceptives may have an impact on female sexuality and female libido. They change serum hormone levels in most women (decreased free testosterone, increased SHBG) without this having a clear effect on libido. But, of course, taking the pill is only one of many factors which affect female sexuality.
Study results provide some evidence that the majority of women should not experience any change in their libido from taking combined hormonal contraceptives; a substantial minority (around 15 – 20%) may experience an improvement or, similarly, a deterioration in their level of sexual desire. There is no unequivocal link between the composition of specific pills or the effect of specific compositions on testosterone/SHBG levels and libido.
Women who take the pill should be informed about the potential impact of the pill on their sexuality.
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5.8 Impact of antiepileptic drugs, antibiotics and antidepressants on the efficacy of hormonal contraceptives
All women who are prescribed enzyme-inducing drugs should be advised to use a reliable form of contraception which will be unaffected by enzyme induction.
Women who do not wish to stop taking combined oral contraceptives during short-term treatment (≤ 2 months) with enzyme-inducing drugs should combine COC with 30 µg ethinyl estradiol, a hormone patch, or vaginal ring, with additional barrier methods. Moreover, an extended or triphasic regimen should be used with an interval of 4 days in which no hormones are taken. Additional methods of contraception should be used for 28 days after discontinuing treatment with enzyme-inducing medication.
With the exception of the very potent enzyme inducers rifampicin and rifabutin, women undergoing long-term treatment (≥ 2 months) with enzyme-inducing drugs who wish to continue taking combined oral contraceptives should increase the ethinyl estradiol dose to 50 µg (max. 70 µg) and continue with this for 28 days after ending treatment with enzyme-inducing drugs. Moreover, an extended or triphasic regimen should be used with an interval of 4 days in which no hormones are taken.
Breakthrough bleeding when simultaneously using COC and taking enzyme-inducing medication may be an indication of a too low serum concentration of ethinyl estradiol. After other potential causes (e.g. chlamydia infection) have been excluded, increasing the EE dose up to a maximum of 70 µg may be considered.
Women who wish to continue using an oral progestogen-only contraceptive or implant during short-term treatment (≤ 2 months) with enzyme-inducing drugs and for 28 days after ending treatment with enzyme-inducing medication should combine taking the pill with additional barrier methods of contraception.
Women taking enzyme-inducing medication who require emergency contraception should be informed about the interactions with oral contraceptives and their potential loss of efficacy and should be offered a copper IUD.
Women requiring emergency contraception who are taking enzyme-inducing medication and for 28 days after ending treatment with enzyme-inducing medication should be recommended to take 3 mg LNG as a single dose (= 2 LNG pills) so quickly as possible, i.e., within 12 h after unprotected sexual intercourse. (According to the package insert, taking LNG > 72 h after unprotected sexual intercourse and taking a double dose of LNG has not been approved.)
Taking ulipristal acetate together with enzyme-inducing drugs or during the 28 days after ending treatment with enzyme-inducing drugs is not recommended.
Women must be informed that ulipristal acetate has the potential to reduce the efficacy of hormonal contraceptives. Additional methods of contraception must be used for 14 days after taking ulipristal acetate (9 days when using or starting to use oral progestogen-only contraceptives, 16 days for dienogest/estradiol valerate) (no drug approval).
Additional methods of contraception are not required when taking antibiotics which do not have an enzyme-inducing effect.
Women must be informed and educated about the proper use of COC when they are ill. Additional methods od contraception are recommended if the antibiotic or illness leads to vomiting or diarrhea.
At the start of taking hormonal contraceptives, when changing hormonal prescriptions, and when ending hormonal contraception, serum levels and efficacy should be checked in women who take medication which interacts with COC. The prescribing physician should be involved in any changes to prescribed medication as this will allow the physician to take appropriate measures.
Women receiving monotherapy with lamotrigine must be informed that both the risk of seizures and the risk of toxicity during the hormone-free days will increase if they are taking COC, meaning that the risks associated with using COC outweigh the benefits ([Table 8]).
|
Method |
Short-term therapy < 2 months |
Long-term therapy > 2 months or difficulty in using additional contraceptive methods |
|---|---|---|
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Combined hormonal contraceptives
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Recommendation: Switch to contraceptive method which is not affected by enzyme-inducing drugs. For example, stop taking COC and use a DMPA depot injection |
Switch to a contraceptive method which is not affected by enzyme-inducing drugs |
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Alternatives: Take COC/d (30 µg EE/d), hormone patch/1 week or vaginal ring/3 weeks with extended or triphasic dosing and a hormone-free interval of 4 days and additionally use barrier method during enzyme-inducing therapy and for 28 days after ending enzyme-inducing treatment plus: use additional contraceptive method (e.g. condoms) when taking enzyme-inducing drugs and for 28 days after ending treatment with enzyme-inducing medication or: follow the recommendations for long-term therapy with enzyme-inducing drugs |
Take COC (at least 50 µg EE) with extended or triphasic dosing and a hormone-free interval of 4 days during enzyme-inducing therapy for 28 days after ending enzyme-inducing treatment Note: This recommendation does not include the enzyme inducers rifampicin and rifabutin! Using 2 patches or rings is not recommended |
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|
Progesterone-only therapy
|
Recommendation: Switch to a contraceptive method which is not affected by enzyme-inducing drugs |
Switch to a contraceptive method which is not affected by enzyme-inducing drugs |
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Alternatives: Continue taking oral progesterone-only pill or progesterone implant and use an additional barrier method during treatment with enzyme-inducing drugs and for 28 days after ending treatment with enzyme-inducing drugs |
No alternatives recommended |
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|
No changes required |
No changes required |
|
Emergency contraception |
||
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Efficacy is unaffected, therefore recommended for all women for whom copper IUD is not contraindicated for the period during which they take enzyme-inducing drugs and for 28 days after ending treatment with enzyme-inducing drugs (0 – 120 h after unprotected SI or within 5 days of expected date of ovulation) |
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3 mg LNG in the form of a single dose to be taken as quickly as possible up to 120 h after unprotected SI (off label) |
|
|
Use of other methods is recommended |
|
|
Non-hormonal methods |
No changes required |
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6 Oncology
6.1 Impact of hormonal contraception on the incidence of breast cancer
Whether hormonal contraceptives increase the incidence of breast cancer is not clear. It is not possible to exclude the possibility of a slightly increased risk both during the period of taking oral contraceptives and after the patient has stopped taking hormonal contraceptives.
Women with and without BRCA 1/2 mutation should be informed about a possibly slightly increased risk of developing breast cancer before they start taking oral contraceptives.
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6.2 Impact of hormonal contraception on the incidence of ovarian cancer
Hormonal contraceptives are associated with a reduced risk of developing ovarian cancer. The risk-reducing effect depends on the duration of intake and has been observed for up to 30 years after the patient stopped taking hormonal contraceptives.
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6.3 Impact of hormonal contraception on the risk of breast cancer recurrence
Whether hormonal contraceptives increase the risk of recurrence in patients who are s/p breast cancer is not clear. It is not possible to exclude the possibility of an increased risk of recurrence.
Hormonal contraceptives should not be prescribed to women who have had breast cancer as the safety of hormonal contraceptives with regard to a risk of recurrence has not been proven.
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6.4 Impact of hormonal contraception on the incidence of cervical cancer
Combined contraceptives are associated with an increased risk of developing cervical cancer during the period in which the contraceptive is taken and for up to 20 years after the patient stopped taking combined contraceptives. The strength of the impact depends on the duration of intake.
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6.5 Impact of hormonal contraception on the incidence of endometrial cancer
Hormonal contraceptives are associated with a reduced risk of developing endometrial cancer. The strength of this impact depends on the duration of intake.
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6.6 Impact of hormonal contraception on the incidence of colon cancer
Hormonal contraceptives are associated with a reduced risk of developing colon cancer.
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Conflict of Interest/Interessenkonflikt
The authorsʼ conflicts of interest are listed in the long version of the guideline./Die Interessenkonflikte der Autoren sind in der Langfassung der Leitlinie aufgelistet.
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References/Literatur
The literature is listed in the long version of the guideline./Die Literatur ist in der Langfassung der Leitlinie aufgelistet.
Correspondence/Korrespondenzadresse
Publication History
Received: 03 September 2020
Accepted: 08 September 2020
Article published online:
08 February 2021
© 2021. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
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References/Literatur
The literature is listed in the long version of the guideline./Die Literatur ist in der Langfassung der Leitlinie aufgelistet.