Pharmacological treatment of male infertility
Because patients with idiopathic male infertility lack a clear etiology, empirical pharmacotherapy is often used for this group of patients. Many studies have found that the current available empirical pharmacological options cannot be proven to have definitive efficacy in patients with idiopathic male infertility. However, there is no denying that empirical pharmacotherapy is still widely used in clinical practice and that some drugs do have a therapeutic effect in some patients. In the course of pharmacotherapy, attention should be paid to the indications for drug use and the timing of treatment as much as possible. If empirical drug therapy is prepared, the duration of drug use should not be less than 3 to 6 months so that a complete spermatogenic cycle can be covered. The commonly used empirical treatment drugs in current clinical practice are introduced as follows: Zhang Nan, Department of Urology, Zhengzhou People’s Hospital
1 Anti-estrogenic drugs
Anti-estrogenic drugs are one of the most commonly used drugs for the treatment of idiopathic oligospermia. These drugs promote the secretion of gonadotropins by the pituitary gland by blocking the negative feedback inhibitory effect of estrogen, which can then increase the serum levels of FSH and LH. They mainly stimulate the production of testosterone by the interstitial cells of the testes, and secondly, they also promote spermatogenesis. Anti-estrogenic drugs are relatively inexpensive and safe to take orally, however, their efficacy remains controversial. Clomiphene and tamoxifen are the most commonly used anti-estrogen drugs in clinical practice.
Clomiphene is a synthetic non-steroidal estrogen with a structure similar to that of hexestrol, which exhibits significant estrogenic effects. It is commonly used at 50mg/d, orally. Excessive doses tend to inhibit spermatogenesis. Blood gonadotropins and testosterone must be monitored to ensure that testosterone is in the normal range.
Tamoxifen (Tamoxifen triamcinolone) has a weaker estrogenic effect than clomiphene, with a dose range of 10-30 mg/d orally.
2 Androgen therapy
Two regimens are often used for the treatment of idiopathic infertility with androgenic preparations: high-dose rebound therapy and low-dose continuous administration. If the hypothalamic-pituitary-gonadal axis is intact, androgen therapy will reduce the intra-testicular testosterone concentration. Treatment with high doses of exogenous testosterone will inhibit the release of LH from the pituitary gland, which in turn will lower intra-testicular testosterone levels. Rebound therapy is desired to improve spermatogenesis through rebound of the gonadal axis after cessation of androgen therapy. Low-dose continuous therapy aims to stimulate spermatogenesis through testosterone supplementation.
3 Antioxidant therapy
Excess reactive oxygen species (ROS) in semen can damage sperm through oxidative stress leading to lipid peroxidation, while antioxidants in seminal plasma have the effect of scavenging ROS and can prevent sperm damage. Based on this principle, clinical oral antioxidants can reduce oxidative stress damage and improve male fertility. Commonly used antioxidants include vitamin E, vitamin C, coenzyme Q10, and acetylcysteine.
4 Tryptokinase-releasing enzyme
It has been used in male treatment since the 1980s. It is believed that pancreatic kinin-releasing enzyme stimulates spermatogenesis and improves sperm motility. Other mechanisms may include improving sperm metabolism, increasing testicular blood supply, stimulating testicular support cell function, and improving the function of gonadal output ducts.
5 Hexanone theobromine (Pentoxifyline)
A derivative of methylxanthine, it is commonly used in the treatment of vascular disease as a non-selective phosphodiesterase inhibitor that blocks the conversion of cAMP to AMP and increases cellular glycolysis and ATP production. The therapeutic mechanism for its use in the treatment of idiopathic infertility is that it may improve testicular microcirculation, reduce cAMP degradation, increase intracellular glycolysis and ATP synthesis and consequently promote sperm metabolism and other functions. Improvements in sperm concentration, viability, and percentage of normal-form sperm have also been reported. Commonly used dose: 1200mg/d.
6α-blockers
Although there is no clear, well-defined pathophysiological concept or theoretical basis for the use of alpha blockers in the treatment of male infertility, placebo-controlled studies have shown that treatment with alpha blockers increases ejaculate volume, sperm concentration, and total motile sperm count.
7 Recombinant human growth hormone (recombinanthu-man-growth, rh-GH)
rh-GH enhances testicular interstitial cell function and increases semen volume. rh-GH stimulates the release of insulin-like growth factor-1
(IGF-1), which acts as an autocrine/paracrine growth factor in the process of sperm growth. Its dose is 2 to 4 IU/d by subcutaneous injection.
8 L-carnitine (L-Carnitine)
Also known as levocarnitine. L-Carnitine in human body is a derivative of lysine further modified by methylation, which is a substance secreted by the epididymis and exists mainly in the free state and acetylated form. It increases sperm energy and sperm motility during sperm transport in the epididymis, and also has some antioxidant capacity to protect sperm from oxidative damage. Currently, levocanidine is widely used as a nutritional additive in the clinical treatment of idiopathic male infertility. Commonly used dose: 1~2g/d, 2~3 times daily, orally.
9 Other drugs
Amino acids, zinc, selenium, vitamin A, and prostaglandin synthase inhibition have been reported experience and may help to improve sperm parameters and conception rate.
Reprinted from the Chinese Guide to the Diagnosis and Treatment of Male Diseases