We agree that obesity-induced hyperandrogenism,

hypothyroidism, hyperprolactinaemia and iatrogenic

hyperandrogenism are all possible causes of virilisation in

women. The aimof our article was not to provide an exhaustive

list of potential causes, but rather to discuss the role of

biochemical testing in the differential diagnosis of

hyperandrogenism and some important limitations in

clinical practice.

References

1 Bell A, Meek CL, Viljoen A. Evidence of biochemical hyperandrogenism inwomen: the limitations of serum testosterone quantitation. J ObstetGynaecol 2012;32:367–71.

2 Barth JH, Field HP, Yasmin E, Balen AH. Defining hyperandrogenism inpolycystic ovary syndrome: measurement of testosterone andandrostenedione by liquid chromatography-tandem mass spectrometryand analysis by receiver operator characteristic plots. Eur J Endocrinol2010;162:611–5.

3 Hahn S, Kuehnel W, Tan S, Kramer K, Schmidt M, Roesler S, et al. Diagnosticvalue of calculated testosterone indices in the assessment of polycystic ovarysyndrome. Clin Chem Lab Med 2007;45:202–7.

4 Cho LW, Jayagopal V, Kilpatrick ES, Holding S, Atkin SL. The LH/FSH ratiohas little use in diagnosing polycystic ovarian syndrome. Ann ClinBiochem 2006;43:217–9.

5 Pasquali R, Vicennati V, Bertazzo D, Casimirri F, Pascal G, Tortelli O, LabateAM. Determinants of sex hormone-binding globulin blood concentrationsin premenopausal and postmenopausal women with different estrogenstatus Virgilio-Menopause-Health Group. Metabolism 1997;46:5–9.

Claire Meek MB ChB BSc(Med Sci) MSc MRCP (on behalf of all authors)

Addenbrooke’s Hospital, Cambridge, UK

Re: The relationship between infertility treatment andcancer including gynaecological cancers

Dear Sir

Louis et al1 are to be commended for the multiple studies

they analysed for their article on the evidence of infertility

treatment and cancer.

We wondered if the authors had considered presenting the

data graphically in a forest (meta-analysis) plot. Furthermore,

as fertility treatments such as clomiphene citrate have been

used for over 50 years, and in vitro fertilisation for over

30 years, we were surprised by the suggestion in the

penultimate paragraph that most of the treated patients

have not reached the age of peak incidence for gynaecological

cancers, given that the average age of infertility is 30 to

35 years and the peak incidence of ovarian cancer is 60 years,

achieving a plateau after the age of 65.

Reference

1 Louis LS, Saso S, Ghaem-Maghami S, Abdalla H, Smith JR. The relationshipbetween infertility treatment and cancer including gynaecological cancers.The Obstetrician & Gynaecologist 2013;15:177–83.

Dr E ScotlandBasildon and Thurruck University Hospital, Basildon, UK

Mr R Haloob MBChB FRCOG MFFP

Basildon and Thurruck University Hospital, Basildon, UK

Authors’ reply

Dear Sir

We thank Dr Scotland and Mr Haloob for their interest in

our article. They raised two important points:

1. The question of whether we should have used a ‘forest

(meta-analysis) plot’. As this is meant to be a review article

and not a meta-analysis study, it negates the need to use

such a plot. Our group, however, is in the process of

analysing each individual cancer separately in a

meta-analysis paper that we hope to publish soon.

2. It is true that a long time has elapsed since clomiphene

citrate (cc) and in vitro fertilisation (IVF) have been in

clinical use, but almost all the studies published so far,

including the largest data to date from the Danish group,1

have a median age at the end of follow-up way below the

peak age for ovarian and uterine cancers. The only study

that has a median age of more than 60 at the end of the

follow-up period was that of Sanner et al,2 with the age

being 61 years, hence our conclusion in the penultimate

paragraph. We apologise if this was not made very clear in

the article. We do stress the need for vigilance and that the

data could change over time.

References

1 Jensen A, Sharif H, Frederiksen K, Kjaer SK. Use of fertility drugs and risk ofovarian cancer: Danish Population Based Cohort Study. BMJ 2009;338:b249.

2 Sanner K, Conner P, Bergfeldt K, Dickman P, Sundfeldt K, Bergh T, et al.Ovarian epithelial neoplasia after hormonal infertility treatment: long-termfollow-up of a historical cohort in Sweden. Fertil Steril 2009;91:1152–8.

Louay S Louis MRCOG

Imperial College London, London, UK

Srdjan Saso MRCS

Imperial College London, London, UK

Sadaf Ghaem-Maghami PhD MRCOG

Imperial College London, London, UK

Hossam Abdulla FRCOG

The Lister Hospital, London, UK

70 ª 2014 Royal College of Obstetricians and Gynaecologists

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