Complicated contraception: Family history as a risk factor

In the third and final part of our mini-series on difficult contraception prescribing scenarios, Dr Toni Hazell discusses the issues to consider in a woman with a family history which may be relevant to her contraception choice

What family history should we routinely take when prescribing contraception?

The reason for taking a history before prescribing contraception is to identify any factors which might affect the choice of what to prescribe. Anyone who prescribes contraception should be aware of the Faculty of Sexual and Reproductive Health (FSRH) UK Medical Eligibility Criteria for Contraceptive use (UKMEC), which divides co-morbidities into four categories. UKMEC category 1 is no contraindication; UKMEC 4 is an absolute contraindication. More nuanced are UKMEC 2 (relative contraindication – benefits usually outweigh risks) and UKMEC 3 (relative contraindication – risks usually outweigh benefits). An experienced prescriber might still prescribe if a method is UKMEC 3, but this would be after a significant discussion, using the principles of shared decision making and with detailed documentation in the notes as to the thought process before prescribing.

The relevant family history is therefore that which might lead to a UKMEC 2-4 for that method:

• Breast cancer – UKMEC 2/3 depending on method if a cancer-causing gene mutation is found.
• Venous thromboembolism (VTE) – UKMEC 2/3 in a first-degree relative for combined hormonal contraception (CHC), depending on age.

How should we approach a patient with a family history of VTE?

This is mainly relevant for CHC – while progestogen-only contraception indicates UKMEC 2 for those who have had a VTE themselves, or who are known to have a thrombogenic mutation, a family history is UKMEC 1 for all contraceptive methods other than CHC.

For CHC (which includes the combined pill, patch and vaginal ring) a VTE in a first-degree relative is UKMEC 2 if they were ≥45 at the time of the VTE, or UKMEC 3 if <45. The obvious solution is to switch to a non-CHC method, but some patients will find this difficult, for example if they have tried all other methods and have experienced unacceptable adverse effects or had unplanned pregnancies when using other methods.

The UKMEC notes that a family history may identify an increased risk but doesn’t confirm that the woman has a thrombophilia. Thrombophilia screening is not felt to be cost-effective in this situation; a negative thrombophilia screen doesn’t fully exclude the risk of any thrombophilia, only for those thrombophilias for which we can currently test.

It is therefore up to us to make a risk assessment, in conjunction with the patient. Factors favouring prescribing might include a clear provoking factor for their relative’s VTE (such as after surgery, during pregnancy/postnatally, or after a long flight), a family history with only a single VTE present, and a patient who has already previously used CHC with no problems. Even if all these are true, the patient would have to understand that the family history does give a relative contraindication and that she must accept that risk. Conversely, if the patient has a family history of multiple relatives with VTEs, particularly if unprovoked, the likelihood that CHC use will be safe must be less.

When would we refer to genetics regarding a family history of breast or ovarian cancer, and how should contraception be managed while the woman is waiting to see the genetics clinic?

Breast cancers can carry hormone receptors for progesterone and/or oestrogen, and so this is relevant for both combined and progestogen-only contraception. The first consideration is whether or not the woman meets the criteria for referral to a genetics clinic. There is NICE guidance on this, which is complex, but the key fact to remember is that if there is only one first- or second-degree relative diagnosed with breast cancer at over the age of 40, then no referral is needed. A caveat to this is that it only applies if none of the following are present in the family history:

• Bilateral breast cancer.
• Male breast cancer.
• Ovarian cancer.
• Jewish ancestry.
• Sarcoma in a relative younger than age 45 years.
• Glioma or childhood adrenal cortical carcinomas.
• Complicated patterns of multiple cancers at a young age.
• Paternal history of breast cancer (2 or more relatives on the father’s side of the family).

The guidance is not clear as to how these factors would influence the decision to refer, but seeking advice from a genetics clinic would be a sensible thing to do if any of them are present. Jewish patients aged over 18 who live in England can also access BRCA testing via the NHS Jewish BRCA testing programme – this is done because those of Jewish ancestry have a significantly higher rate of BRCA gene mutation carriage than those of different ancestries. Be aware also that those who are ‘Greenlanders’ (not defined in the guidance but might reasonably be interpreted as having a family who comes from Greenland) are at an increased risk of BRCA carriage and such an ethnic background might lower your threshold to refer to a genetics clinic; there is no similar self-referral for those from Greenland as there is for the Jewish population.

If your patient meets the criteria for a genetics referral, then she might want to consider the relative UKMEC contraindications for someone confirmed to have a gene mutation such as BRCA 1 or 2. These gene mutations are a UKMEC 2 for progestogen-only contraception, and UKMEC 3 for CHC, whereas a family history alone with no confirmed gene mutation is UKMEC 1 for both.

Decisions will therefore vary depending on the woman’s attitude towards risk, given the possibility of an undiagnosed BRCA mutation, and you might want to mention that the UKMEC category 3 for CHC is based on a cautious interpretation of evidence, with the guidance stating that ‘the very limited evidence in this area suggests that the risk of breast cancer among women with either a family history of breast cancer or with known inherited breast cancer gene mutations is probably not modified by the use of combined oral contraception’.

The FSRH guidance on combined contraception gives a little more detail, saying that ‘the evidence regarding whether CHC use further increases the risk of cancer for these women is inconsistent, with some systematic reviews/meta-analyses reporting conflicting findings among the studies considered and others finding no increased risk with CHC use’.

For those with only a family history of ovarian cancer, NICE advises genetics referral for all who have a first- or second-degree relative with ovarian cancer; if such a referral results in the diagnosis of BRCA carriage then the same UKMEC contraindications would apply as mentioned above.

Sources and further reading

• FSRH. UK Medical Eligibility Criteria for Contraceptive use (UKMEC). 2019
• FSRH. Combined hormonal contraception. Oct 2023
• NICE. Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer. [CG164] Nov 2023
• NICE. Ovarian cancer: identifying and managing familial and genetic risk. [NG241] March 2024
• Jnetics. The NHS Jewish BRCA Testing Programme.