Hormonal profile in women of childbearing age was believed to have a role in the pathogenesis of IIH. However, to date, there is no established hormone profile in individuals with IIH . The aim of our work was to assess CSF leptin, serum leptin, estradiol, testosterone, Dehydroepiandrosterone sulfate (DHEAS) levels in patients with IIH.
In our study, Only newly diagnosed IIH patients who did not start acetazolamide treatment were included, to avoid the effect of carbonic anhydrase inhibitors on decreasing the CSF pressure and to avoid its effect on reducing weight as discussed by Woodman and colleagues who assumed that acetazolamide, a strong inhibitor of carbonic anhydrase, would reduce chloride/bicarbonate co-transport and decrease food intake, stimulate locomotion, and reduce weight gain from emotional eating .
In the present study, our results revealed that IIH patients had significantly higher levels of serum and CSF Leptin than controls. In agreement with our findings, Behbehani et al. who reported a significant elevation of serum leptin in IIH cases compared to controls (P < 0.05) . Similarly, Ball et al., found that serum and CSF leptin levels were significantly higher in IIH patients compared to controls (P < 0.001) . Although leptin hormone induces satiety, its levels was found to be increased in overweight persons, who are at higher risk to have IIH. This supports the theory of increased leptin resistance in such population [18, 19].
The exact mechanism by which leptin could induce IIH remains unclear. However, some researchers believe that chronic CSF leptin elevation could increase Na/K ATPase activity in the choroid plexus, leading to increased CSF secretion .
On the other hand, other authors negated any significant difference between IIH cases and controls regarding serum leptin (P value < 0.05) . Another small study confirmed the non-significant difference regarding CSF leptin levels in IIH cases and controls . The disparity between different studies could be explained by different CSF leptin measurement assay, variation of CSF leptin level if measured over 24 h period, or exposure to some drugs affecting its levels [21, 22].
In the present study, IIH patients had significantly higher levels of serum estradiol than controls. Farukhi et al., stated that estradiol can induce increased permeability rates of aquaporin-1 when compared to estrone and estriol. As estradiol is the main circulating estrogen form during the child bearing period, the hormonal preference of AQP-1 may explain the increased prevalence of idiopathic intracranial hypertension in women of childbearing period .
In contrast to our findings, other authors negated the significant elevation of estradiol levels in IIH cases . Surprisingly, another study reported that estrogen and progesterone could decrease CSF production by the choroid plexus, either individually or in combination .
In the current study, serum testosterone showed a significant elevation in IIH cases compared to controls (P < 0.001). Likewise, O’Reilly et al., confirmed these findings regarding serum testosterone, as it had a median value of 1.7 (range 1–2.4) nmol/ml in IIH cases and 1 (0.5–1.4) nmol/ml in controls, with a high significant difference between the two groups (P < 0.001) . Moreover, it was reported that about 39–57% of IIH patients have polycystic ovary syndrome (PCOS) which is characterized by androgen overproduction [27,28,29].
Our results showed that serum DHEAS was not significantly different between IIH cases and controls (P = 0.142). In line with our findings, O’Reilly et al., negated any significant difference between IIH and controls regarding serum DHEAS (P > 0.05) .
In the present study, IIH patients with BMI ≥ 30 g/m2 had significantly higher levels of serum Leptin, CSF Leptin, serum estradiol, serum testosterone, and serum DHEAS than IIH patients with BMI < 30 g/m2.
In accordance to our findings, Behbehani et al. reported that serum leptin level was significantly elevated in patients with higher BMI (P = 0.017) . On the other hand, Ball and colleagues negated any significant correlation between leptin levels (serum or CSF) and BMI in patients with IIH. However, a significant positive correlation was noted regarding these variables when applied in controls . Klein et al., reported insignificant impact of BMI in IIH cases on serum estradiol (P value = 840), testosterone (P value = 0.952) or DHEAS levels (P = 0.511) .
Our study has some limitations, first of all, it is a single center study that included a relatively small sample size. Second, the effect of weight loss on the studied parameters was not investigated. We recommend that the upcoming research should focus on the molecular mechanisms by which these hormonal changes could induce this increase in intracranial pressure.