Letrozole versus testosterone for promotion of endogenous puberty in boys with constitutional delay of growth and puberty: a randomised controlled phase 3 trial

Is There Room for SERMs or SARMs as Alternative Therapies for Adult Male Hypogonadism?

“…Furthermore, since the effects of both drugs were similar in young and elderly men, it can be hypothesized that an increased negative feedback by endogenous oestrogens is not instrumental in age-related decline of Leydig cell function in elderly men [13]. Similarly, letrozole (2.5 mg/day for 6 months) was able to promote the development of puberty in boys with constitutional delay of growth and puberty, further emphasizing the functional role of the impairment of the hypothalamic-pituitary-testis axis in this clinical condition [6].…”

“…Hence, according to the results obtained in infertile women treated with either selective estrogen receptor modulators (SERMs) (i.e., clomiphene citrate) or aromatase inhibitors (AIs) (i.e., anastrozole or letrozole), which proved to enhance the serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), men with secondary functional hypogonadism were treated with the same drugs in order to increase the endogenous T levels [6]. On the contrary, both SERMs and AIs maintain the fertility, avoiding the block of spermatogenesis, as TRT does [7,8].…”

Anti-Müllerian hormone and letrozole levels in boys with constitutional delay of growth and puberty treated with letrozole or testosterone

“…Indeed, iB has been suggested to be at least partially gonadotrophindependent in early puberty (Grinspon et al, 2013). Another intriguing finding was that the Lz-treated boys had larger testes 6 months after the treatment than those who received low-dose T, although the iB levels did not differ at that time point (Varimo et al, 2019). To better understand the putative effects of Lz and low-dose T on the developing seminiferous epithelium, we now report serum levels of anti-Müllerian hormone (AMH), which is another Sertoli cell product and a suggested surrogate marker for Sertoli cell number and function (Grinspon et al, 2018).…”

“…We have recently described a new treatment approach for boys with CDGP: a 6-month regimen of peroral aromatase inhibitor letrozole (Lz) (2.5 mg/day), which is more efficacious in inducing hypothalamicpituitary-gonadal (HPG) axis activity and testis growth than the lowdose testosterone (T) treatment (Varimo et al, 2019). Lz, which accelerated height growth, may thus provide a new peroral treatment option for boys with CDGP.…”

“…Although aromatase inhibitors have been employed in paediatric studies aimed to increase adult height (Wickman et al, 2001;Hero et al, 2005;Mauras et al, 2008;Mauras et al, 2016;Leschek et al, 2017), and in treating rare conditions causing estrogen excess (Wit et al, 2011), there are no reports on circulating Lz levels in paediatric patients. The randomised, controlled studies from our centres have employed a fixed daily dose of 2.5 mg (Hero et al, 2005;Varimo et al, 2019), same as that used in adults, and it might be possible to achieve the desired treatment effects (i.e. HPG axis activation) with a smaller dose as well.…”