Members Evidence Request - Supporting Clinical Practice

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 members evidence request service, please log in to ‘My FSRH’ and click on ‘Members' evidence request’ 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. View a video on how to register on our website here

Example Question One

Diethylstilboestrol (DES) and combined hormonal contraception
What are the risks to a young woman whose relative (great grandmother) took Diethylstilboestrol (DES) whilst pregnant and whose grandmother (exposed in utero) developed various gynaecological cancers? This young woman wishes to commence contraception and has been warned that there may be problems with oestrogen. Is this correct?

Diethylstilbestrol (DES) is a synthetic estrogen that was widely prescribed in the 1940s to 1960s as treatment to reduce the risk of miscarriage. The association between exposure to DES in utero and clear cell adenocarcinoma of the vagina and cervix was established in the 1970s leading to further and ongoing research into the long-term effects of DES on the children (DES sons and daughters) and grandchildren (DES grandchildren) of women who took DES in pregnancy. [1] Associations have also been identified with infertility, structural abnormalities of the genital tract and adverse pregnancy outcomes in DES daughters and an association with breast cancer has also been suggested.

Are DES grandchildren and great-grandchildren at increased risk of adverse health events?
The CEU conducted a literature review. Evidence relating to adverse health events in descendents of women who were DES-exposed in utero (DES daughters) is very limited.

The U.S. DES follow up study reported a possible association between a woman’s own in utero exposure to DES and birth defects in her offspring (DES grandchildren) [2]; there was no apparent overall increase in cancer risk in DES grandchildren, no increase in vaginal or cervical cancers and although there was a greater than expected incidence of ovarian cancer, this was based on a total of 3 cases. [3] The study reported a high risk of reproductive dysfunction in DES daughters but not in DES granddaughters [4]; however it is noted that at the time of the study most of the cohort of DES granddaughters had yet to start their families. The preliminary findings of the study also suggest higher risk of menstrual irregularity and infertility in DES-granddaughters. There is significant risk of reporting bias in these studies and findings are based on very small number of cases U.S. studies suggest an increased risk of breast cancer in DES daughters after age 40, but European studies (with younger cohorts) found no association. [5]. Animal models have suggested that DES granddaughters could be at increased risk of breast cancer [6]; however this remains speculative and the very limited evidence from human studies has not demonstrated an association.[5]

What do we know about contraceptive use by DES-exposed women and their descendents?
There are no published studies that examine the safety of hormonal contraception use by DES daughters, granddaughters and great-granddaughters. In the absence of evidence, the CEU is unable to make any comment regarding the safety of use of any hormonal contraceptive by a woman whose grandmother was exposed to DES in utero.

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Example Question Two

I have a woman on cerazette who is taking 25mg topiramate bd for migraine Is it still advised at a low dose that she uses a different form of contraception or does under 200mg of topiramate be regarded as ok?

Pharmacokinetic studies, such as those cited in the Summary of Product Characteristics (SPC) for topiramate indicate that topiramate induces CYP3A4 enzyme activity in a dose-dependent manner; the evidence suggests that low dose topiramate does not significantly reduce exposure to contraceptive hormones. However there is inadequate evidence from clinical studies that directly assess the contraceptive effectiveness of hormonal contraception during use of topiramate at different doses to be certain at what dose there might be a clinically significant effect on pregnancy risk. FSRH Guidance Drug Interactions with Hormonal Contraception therefore does not distinguish between low and high dose use of topiramate in relation to potential drug interactions with hormonal contraceptives.

FSRH Guidance recommends that women currently using, or within 28 days of stopping use, of an enzyme inducer should not rely on oral hormonal contraception, patch, ring or progestogen-only implant. DMPA, IUS and IUD are effective alternatives.

Example Question Three

I have a patient who has otosclerosis (as does her mother). She says she has been told in the past that she should avoid hormonal contraception due to the otosclerosis, however wishes to use a more reliable method than condoms. Otosclerosis is not mentioned in the UKMEC or any of the guidelines. Please could you advise if there is any evidence that any hormonal methods should not be used in women with otosclerosis?



Case reports relating to otosclerosis in users of oral contraceptives (OC), together with an apparent association between parity and otosclerosis have led authors to suggest that there could be an association between OC use and development of otosclerosis.

The evidence that exists is very limited. Data from the Oxford FPA study cohort, which observed 31 cases of otosclerosis identified no association between OC use and otosclerosis; numbers of cases are, however very small which limits the conclusions that can be drawn.

Similarly, in a cohort of 600 OC users aged 16-30, Podoshin et al, reporting in 1978 identified 3 cases of otosclerosis at baseline, an incidence (0.5%) that would be expected in the general population. No new cases were observed during ongoing use. As this article was unavailable to access, it is not known if the women with otosclerosis were already OC users at baseline or how long they continued to use.

Evidence is not identified regarding the effect of contraceptive hormones on existing otosclerosis. It is recommended that you seek expert advice from the clinician managing the woman’s otosclerosis.

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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.