Co-morbid Polycystic Ovarian Syndrome with Idiopathic Intracranial Hypertension

ABSTRACT

The link between polycystic ovarian syndrome (PCOS) and idiopathic intracranial hypertension (IIH) has long been debated. Historically, there is a wide range of reported occurrence of both conditions, being between 15% and 64%. Both conditions share a common phenotype. The awareness that in a new large data study that there is a 1.5-fold increased prevalence of diagnosed PCOS in participants with IIH as compared to the controls is important. Assessment for the potential of co-morbid PCOS in women with IIH is important as this may enable optimisation of weight and fertility management.

Dear Editor,

Idiopathic intracranial hypertension (IIH) typically affects reproductive aged women with obesity.^1,2 The manifestations of this disease are increasingly being identified beyond the traditionally known headache and visual symptoms.^3,4 The link between polycystic ovarian syndrome (PCOS) and IIH has long been debated. Case series suggest co-existence of the two conditions in 15–64% of women with IIH.^5–8 Both are phenotypically similar with systemic metabolic dysfunction,^9–13 truncal adiposity,^13–15 insulin resistance,^9,12 reduced fertility,^16–18 gestational complications,^16,19 and an increased cardiovascular risk.²⁰ They are hyperandrogenic disorders but with distinct hormonal signatures.²¹ The prevalence of co-morbid PCOS in IIH compared with age- and body mass index-matched controls has not been previously assessed.

In a recent population-based longitudinal cohort study of >50,000 women that evaluated medication prescribing habits in women with IIH (n = 3411) and population controls (n = 33,495) was recently published in Neurology.²² It reported that a higher proportion in the IIH group had PCOS (7.4%) compared with matched population controls (4.9%) at study entry,²² corresponding to a 1.5 - fold increased prevalence of diagnosed PCOS in participants with IIH compared with the controls. This is similar to Avisar et al., who showed a 1.8-fold increase of 15.5% PCOS in IIH versus 8.9% in their general population.⁵

The 1.5 - fold increased prevalence of co-morbid PCOS in IIH is an important finding and supports this more recent literature⁵ and refutes the earlier overestimations reported.^6–8 This is important as it may influence weight and fertility management, e.g. metformin aids weight loss when both diseases are present.⁶,35

Weight gain is a key precipitant in the development of IIH,²³ and a recent randomised control trial has shown the benefit of weight loss in lowering raised intracranial pressure and inducing remission of the condition.²⁴ Weight loss targets of 5–10% are often reported and this is based on the general obesity literature,²⁵ but in clinical practice the amount required is variable and often higher amounts are required.^24,26,27 This can be even more challenging in certain scenarios, including pregnancy.²⁸ Weight loss in PCOS has been achieved through: lifestyle management²⁹; medical management, e.g. orlistat,^30–32 metformin,^31,32 and glucagon-like peptide-1 receptor agonists³³; and bariatric surgery, especially in those unresponsive to lifestyle management or medical treatment.²⁶ Medical management of co-morbid PCOS may aid the weight loss required for IIH disease control. Metformin has been shown to aid weight loss in IIH where comorbid PCOS is present,⁶ although this is not part of routine clinical care and is not currently recommended for IIH management.³,34

Additional ovulatory benefits have been shown for weight loss prior to pharmacotherapy use for infertility.^34,35 Where fertility issues are present, the use of medications, e.g. clomiphene citrate, letrozole, or metformin, is recommended.¹⁷ These could be beneficial in this illustrated combined cohort.

We recommend assessing for the potential of co-morbid PCOS in IIH patients as this may enable optimisation of weight and fertility management options. What is yet to be determined is whether the combination of these disorders confers additional risks to vision, headache or cardiovascular morbidity.

Funding Statement

Medical Research Council (MRC) [MR/K015184/1]; The Midland Neurosciences and Teaching Research Fund.

Disclosure statement

S.P. Mollan reports other funding from Invex Therapeutics and Heidelberg engineering during the conduct of the study and other funding from Chugai-Roche Ltd., Janssen, Allergan, Santen, Roche, and Neurodiem outside the submitted work. A.J. Sinclair reports personal fees from Invex therapeutics during the conduct of the study. All other authors report no conflict of interest.