Idiopathic hirsutism:Is it really idiopathic or is it misnomer?

Hirsutism,which is characterized by excessive growth of terminal hair in a male pattern,may result from various causes including polycystic ovary syndrome(PCOS),non-classic congenital adrenal hyperplasia,adrenal or ovarian tumors or it may be idiopathic.Idiopathic hirsutism is currently defined as hirsutism associated with normal ovulatory function,normal serum androgen levels and normal ovarian morphology,however,the pathogenesis of idiopathic hirsutism is not clear.The androgens are the main hormones to stimulate growth of body hair,therefore,there should be any form of increased androgen effect irrespective of normal serum androgen levels in any patient with hirsutism.In accordance to this scientific truth,we have previously shown that,although within normal limits,patients with idiopathic hirsutism have relatively higher serum androgen levels(relative hyperandrogenemia)in comparison to healthy subjects which let as to think that is idiopathic hirsutism really idiopathic?In addition to relative hyperandrogenemia,we have previously shown that,in comparison to healthy subjects,women with idiopathic hirsutism demonstrated higher expression of steroid sulphatase and 17-beta hydroxysteroid dehydrogenase mRNA both in the subumbilical region and arm skin,which contributes to local androgen metabolism.Those results support the idea that,in some patients,although the adrenals or ovaries do not secrete increased amount of androgens leading to hyperandrogenemia,pilocebaceous unit locally produce increased amount of androgens leading to hirsutism without ovulatory dysfunction.Upon the demonstration of relative hyperandrogenemia and possible increase in local androgen synthesis in patients with idiopathic hirsutism,we think that idiopathic hirsutism is not idiopathic and it may be named as“normoandrogenic hirsutism”.Furthermore,it may not be a different entity but may be an early stage of hyperandrogenic disorders such as PCOS.Clinically,this can be find out by following-up patients with idiopathic hirsutism prospectively.

Role of insulin and insulin resistance in androgen excess disorders

Insulin has complex effects on cell growth,metabolism and differentiation,and these effects are mediated by a cell-surface bound receptor and eventually a cascade of intracellular signaling events.Among the several metabolic and growth-promoting effects of insulin,insulin resistance is defined as an attenuated effect of insulin on glucose metabolism,primarily the limited export of blood glucose into skeletal muscle and adipose tissue.On the other hand,not all the signaling pathways and insulin-responsive tissues are equally affected,and some effects other than the metabolic actions of insulin are overexpressed.Ovaries and the adrenal glands are two examples of tissues remaining sensitive to insulin actions where insulin may contribute to increased androgen secretion.Polycystic ovary syndrome(PCOS)is the most common form of androgen excess disorder(AED),and its pathogenesis is closely associated with insulin resistance.Patients with idiopathic hirsutism also exhibit insulin resistance,albeit lower than patients with PCOS.Although it is not as evident as in PCOS,patients with congenital adrenal hyperplasia may have insulin resistance,which may be further exacerbated with glucocorticoid overtreatment and obesity.Among patients with severe insulin resistance syndromes,irrespective of the type of disease,hyperinsulinemia promotes ovarian androgen synthesis independently of gonadotropins.It is highly debated in whom and how insulin resistance should be diagnosed and treated among patients with AEDs,including PCOS.It is not suitable to administer an insulin sensitizer relying on only some mathematical models used for estimating insulin resistance.Instead,the treatment decision should be based on the constellation of the signs,symptoms and presence of obesity;acanthosis nigricans;and some laboratory abnormalities such as impaired glucose tolerance and impaired fasting glucose.