Talking about why Letrozole can be used to treat male infertility Many infertile men are often filled with guilt and frustration when they learn that it is their own sperm problem that is causing their wives to fail to conceive. At this point, the prescription prescribed by the male physician according to their condition is undoubtedly a very high hope. But many of our friends are often dumbfounded when they take a closer look at the medication: some of the indications on the medication only state that it is for the treatment of female diseases, but there is no mention that it can be used to treat male infertility! So is it better to listen to your doctor or to follow the indications strictly and give up taking the medication? Let’s take Letrozole as an example to illustrate. Letrozole is used in male medicine to treat oligospermia and even azoospermia, and it is also often used as an ovulation stimulant in female medicine of assisted reproduction. However, in the indication section, it only says “as adjuvant therapy for early postmenopausal breast cancer patients” in black and white! Why does the same drug work in a very different disease? Why does the same drug work in very different diseases? It starts with its mechanism of action. Letrozole is an aromatase inhibitor that prevents aromatase from converting androgens into estrogen, thus reducing estrogen levels in the body. When the estrogen level in breast cancer patients is low, the tumor is less likely to recur. In contrast, low estrogen levels in men with infertility affect the negative feedback of the pituitary-hypothalamus-gonadal axis. The pituitary gland receives this signal and accelerates the release of GnRH, which in turn promotes the release of LH and FSH hormones from the hypothalamus: FSH acts directly on the varicocele to promote spermatogenesis; LH acts on the testicular mesenchymal cells to increase the secretion of androgens and to raise estrogen levels in the body through the conversion of aromatase. However, the effect of letrozole in blocking the conversion of androgens to estrogens significantly increases the ratio of androgens to estrogens in the body: the increased concentration of androgens acting on the varicocele greatly enhances spermatogenesis in cooperation with FSH. A foreign study reported that infertile men with oligospermia treated with letrozole, taking 2.5 mg daily, serum estrogen levels were suppressed and testosterone increased from 14 nmol/L to 28 nmol/L after 3 months. correspondingly, semen quality also improved significantly, with sperm concentration rising from 5.5×106/ml to a normal level of 15.6×106/ml! In our clinical experience, some patients with non-obstructive azoospermia also showed small amounts of sperm in semen specimens after treatment with letrozole! In fact, it is very common in the medical field to use drugs to treat diseases that are not listed in the indications, and there is a special name for off-lable use. There are many, many examples of this, too numerous to mention. For example, aspirin, the most commonly used aspirin, has been used clinically for a century as an antipyretic and analgesic. When its antiplatelet pharmacological mechanism was elaborated in the 1970s, it was used off-label for the prevention of cardiovascular diseases such as heart attacks and strokes. It was not until 1998 that the FDA expanded the indications and formally wrote them into the manual. Therefore, male friends with infertility need not worry at all, male medicine is an emerging discipline, many drugs such as triamcinolone acetonide and tamoxifen have not yet been added to the scope of treatment of male infertility by expanded indications, but the clinical application for many years has been proven to be effective and safe. It is worthwhile to cooperate with your doctor and take the medication as prescribed to have a healthy baby and a bright future for yourself and your family!