Members Enquiry Service
The Clinical Effectiveness Unit (CEU) provides an evidence-based enquiry service for FSRH members. The CEU will conduct a literature review and summarise the available evidence in relation to a particular medical condition and/or contraceptive method.
Recent Questions and Answers that have been submitted to the CEU can be seen below. Please note, the full answer includes references to more information and guidance.
To gain access to the enquiries service, please log in to ‘My FSRH’ and click on ‘My Clinical Enquiries’ to search for questions or submit your own question. This service is available to current FSRH members. If you are an FSRH member and have not yet created your ‘My FSRH’ account, please click the ‘Register’ button on the top right of this website and follow the steps to gain access to your account.
Example Question One
I have been asked for advice by a colleague regarding providing contraception for a patient with Variegate Porphyria. The patient is young and nulliparous. She has tried an IUS but after 3 weeks she started experiencing severe pain and attended A&E where the IUS was removed. I have no further information regards her disease activity.
The British National Formulary (BNF) advises that in women with acute porphyria—including variegate porphyria (VP)—hormonal contraception is considered unsafe. They state, “[p]rogestogens should be avoided whenever possible by all women susceptible to acute porphyria; however, when non-hormonal contraception is inappropriate, progestogens may be used with extreme caution if the potential benefit outweighs risk. The risk of an acute attack is greatest in women who have had a previous attack or are aged under 30 years. Long-acting progestogen preparations should never be used in those at risk of acute porphyria.”
The British Porphyria Association advises that a copper intrauterine device (Cu-IUD) or a levonorgestrel intrauterine system (LNG-IUS) may be considered for women with acute porphyrias. LNG-IUS work locally and release a small amount of progestogen into the bloodstream.[3,4] The Association warns that if a woman has already suffered an acute attack, the Cu-IUD may be a safer option.
The CEU conducted a review of a literature and found few articles regarding hormonal contraception use in women with acute porphyrias. A 25-year-old study evaluated all known individuals with acute intermittent porphyria (AIP) and VP in Finland over a period of 20 years. 44 of the 95 women in the study (46%) had used exogenous hormones, of which 37 used contraception of unspecified formulations. Two of the women who used hormones had an acute attack, although it is not clear whether there was direct causation. A retrospective Swedish study of 166 women with AIP reported that 58% of women used oral contraception (85 used combined hormonal contraception [CHC] and 9 used progestogen-only pills [POP]), 10 women used a LNG-IUS and 4 women used a progestogen-only injection. Ten of the women using CHC (11.7%) reported that their contraception provoked an attack while 2 POP users (22%), 0 LNG-IUS users and 1 injectable user (25%) reported provocation. The clinical significance of these findings are limited by small numbers and retrospective self-reporting.
Based on the available evidence, the CEU would recommend that a Cu-IUD be considered first-line contraception for a woman with acute porphyria. If that method is unsuitable or unacceptable to the woman, the CEU recommends liaising with the woman’s specialist regarding LNG-IUS use.
Example Question Two
A 42 year old lady has been identified as having essential thrombocythaemia (platelets 573) for which aspirin 75 mg has been suggested for 'increased thromboembolic risk.' Her haematologist however doesn't seem to think there is an issue with the COC (which appears to be contradictory). The patient is very keen to continue CHC, despite exploring alternatives at length.
Essential thrombocythemia (ET) is a myeloproliferative disorder that causes an overproduction of platelets. ET can cause increased megakaryocyte production, splenic enlargement and bleeding and/or clotting problems. Development of a blood clot may be the first indication of an individual having ET.-2 Current data show that venous thrombosis, transient ischemic attacks, myocardial infarctions and arterial thrombosis are very frequently reported (80-99% of cases) in individuals with this condition.
The CEU conducted a review of the literature and found limited evidence regarding contraceptive use by women with ET. A retrospective cohort study of 305 women aged 16-88 with ET compared 54 women using either hormone replacement therapy (HRT) or combined oral contraception (COC) with 246 women not using estrogen. COC users (n=16) had a five-fold increased risk of venous thrombosis compared with non-users, however the small numbers limit the findings. One review of myeloproliferative neoplasms stated that increased age and use of oral contraceptives increase risk of thombosis in women with ET.
The CEU would suggest that, given that there are effective methods of contraception that are not associated with an increased risk of thrombosis, women with ET should be advised to avoid combined hormonal contraception.
Example Question Three
Is there any evidence for alcohol affecting contraception, due to liver enzyme effect. If so any guidelines as to amounts?
Stockley’s Drug Interaction Checker does not list an interaction between alcohol and contraceptive hormones.
The CEU’s understanding from the literature is that estrogen and progestogen are metabolised via the cytochrome P450 isoenzyme system. They are substrates for CYP isoenzymes 3A4 (and CYP2C9 and CYP1A2).[2,3] Medications that induce these isoenzymes (e.g. carbamazepine) could increase the rate of metabolism of contraceptive hormones and potentially reduce their effectiveness.
Acute alcohol use can inhibit, and chronic alcohol use can induce, the CYP isoenzyme for which it is a substrate, CYP2E1. Contraceptive hormones are not listed as substrates for this enzyme.
The CEU can find no evidence of an effect of alcohol on liver enzyme activity that could potentially reduce contraceptive effectiveness of hormonal contraception.
Please note: The advice given by the CEU should be considered as guidance only and is meant to be used alongside clinical judgement to guide clinical practice or policy. Questions that are a matter of clinical judgment and not evidence should be directed to local sexual and reproductive health leads.