Sexual dysfunction and infertility caused by clinical drug therapy are now common. Commonly, the damage to reproductive function in drug therapy (also called pharmacogenic damage) is mainly manifested as: erectile dysfunction, ejaculatory disorders, abnormal penile erection, loss or disappearance of libido, gynecomastia, male infertility and female infertility, and menstrual irregularities in men. Although pharmacogenic sexual dysfunction is not life-threatening, it can affect the quality of sexual life and the ability to conceive, as well as the adherence to drug therapy. Therefore, drug-induced sexual dysfunction must be given sufficient attention by physicians and pharmacists. At the same time, patients should also learn something about this.
1, diuretic drugs
Many diuretics have different effects on human sexual function, and there are differences with the size of the dose and the length of time used.
(1) thiazide diuretics: hydrochlorothiazide, chlorothiazide and other long-term use, can cause male patients to sexual dysfunction, such as reduced libido, premature ejaculation, erectile dysfunction, etc. The mechanism may be related to drug-induced increase in blood sugar and drug-induced potassium depletion.
(2) Potassium-protective diuretics: spironolactone has anti-androgenic effects, and its long-term use is likely to cause decreased libido and erectile dysfunction in men, and can cause breast development. Another 100~200J of spironolactone daily can cause amenorrhea in women, which mainly inhibits the binding of dihydrotestosterone and androgen receptors.
(3) carboxylic acid potassium-removing diuretics: furosemide, diuretic acid, bumetanide and other long-term use, can cause male sexual dysfunction and breast development.
2.Anti-hypertensive drugs
Erectile dysfunction and ejaculatory dysfunction occur more commonly in patients using antihypertensives than in untreated patients, and the incidence of erectile dysfunction depends on the type of antihypertensive drug.
(1) Central antihypertensive drugs: Colistin and methyldopa can cause loss of libido, erectile dysfunction, and non-ejaculation. The mechanism is agonism of central postsynaptic membrane α2-adrenergic receptors, activation of inhibitory neurons, inhibition of blood catecholamines and insulin, leading to hyperglycemia and impaired glucose tolerance, which has an effect on male sexual function. It also activates α2 receptors in the presynaptic membrane of peripheral adrenergic nerves, resulting in a decrease in negative feedback release of norepinephrine, so that it can cause erectile dysfunction while lowering blood pressure. Methyldopa has the characteristic of causing hyperprolactinemia, which can lead to gynecomastia.
(2) Norepinephrinergic nerve blocking drugs: Risperdal can deplete the mediators of sympathetic nerve endings and cause depression in hypertensive patients, thus reducing libido, which can lead to erectile dysfunction in patients with long-term use, as well as gynecomastia and breast overflow: guanethidine acts partly by the same mechanism as risperdal, but also inhibits the release of norepinephrine and prevents its uptake, and its effect on sexual function The degree of inhibition is related to the dose taken. A daily dosage greater than 25J can cause delayed or no ejaculation in male patients with 50G~60G and erectile dysfunction in patients with 20G~25G.
(3) adrenergic receptor blocking drugs: indolamine, prazosin, pranalol, timolol, labetalol, atenolol and other drugs can cause male hypoactive sexual desire, penile erectile dysfunction, the mechanism of action is the drug to make the blood pressure drop, thus causing a decrease in the perfusion pressure of the penis or direct action on the smooth muscle of the penis. beta-blockers can cause a decrease in blood testosterone levels β-blockers can cause a decrease in blood testosterone levels, and can also affect sexual behavior through the 5-hydroxytryptamine receptor pathway in the central nervous system.
(4) Calcium antagonists: nifedipine, nimodipine, flunarizine, etc. can reduce intracellular calcium concentration by blocking calcium channels, which can potentially alter erectile and ejaculatory function, and can also cause breast development.
(5) Angiotensin-converting enzyme inhibitors: long-term use of captopril can lead to erectile dysfunction and breast tenderness, the mechanism of which may be due to the drug’s reduction of peripheral resistance and blood supply to the reproductive organs. Another angiotensin II receptor blocker valsartan may also cause abnormal sexual function such as: erectile dysfunction, premature ejaculation, etc.
(6) vasodilators: hydrazinpyridazine, minoxidil can cause male sexual dysfunction, can return to normal after discontinuation, but the mechanism of action is not very clear.
3.Lipid-lowering drugs
The current use of a variety of lipid-regulating drugs after long-term application may cause decreased libido, sexual frigidity, penile erectile dysfunction and abnormal penile erection. Clofibrate interferes with the metabolism of androgens, which leads to erectile dysfunction and decreased libido. Gemfibert, fenofibrate, benzofibrate and simvastatin can lead to sexual dysfunction, and their mechanism may be related to the reduction of testosterone level.
4.Hormone
Ethylene estradiol, a synthetic estrogen, is mainly used to prevent preterm abortion and habitual abortion. Pregnant women who apply ethylene estradiol in early pregnancy will interfere with the development of fetal gonads, reproductive organs and vulva differentiation, which will feminize males and cause short penis, hypospadias, epididymis, testes and sperm abnormalities, and even cause hydrocephalus and cerebrospinal bulge, thus leading to male sexual dysfunction and low fertility. Long-term use of estradiol, ethylene estradiol and ethinyl estrone in men can lead to decreased libido, ejaculatory dysfunction and even penile erectile dysfunction. Adrenocorticotropic hormone can interfere with gonadal function, thereby inhibiting spermatogenesis, leading to spermatogenic disorders and penile erectile dysfunction .
5, treatment of prostaglandin hyperplasia drugs
Finasteride and Elistosterone are 5α-reductase inhibitors, which can inhibit the conversion of testosterone to dihydrotestosterone in the serum, thus decreasing the level of dihydrotestosterone and leading to sexual dysfunction and breast enlargement. In addition, drugs for the treatment of prostate cancer, such as gonadotropin, goserelin and flutamide, can lead to erectile dysfunction, decreased libido and enlarged male breasts, the mechanism of which may be to inhibit androgen secretion or prevent the action of androgens.
6.Anti-tumor drugs
The damage of antineoplastic drugs to the testis is mainly in the epithelium of the seminiferous tubules. As the spermatogonia in the differentiation stage are the most active, they are also the most sensitive to cytotoxic drugs, even at low doses.
7.Antihistamines
(1) receptor blocking drugs: diphenhydramine, promethazine, cycloheximide, paracetamol, etc. can cause hypersexuality, mainly because such drugs have varying degrees of central nervous system inhibition, anticholinergic effect and inhibition of parasympathetic nerve action.
(2) receptor antagonists: cimetidine and ranitidine can cause sexual dysfunction, with erectile dysfunction, loss of libido, breast pain and breast milk. The incidence is higher in cimetidine users, especially with high-dose long-term use. While the incidence of ranitidine is low, generally in 7-15d after the use of the drug to varying degrees of hypogonadism symptoms, the mechanism is mainly due to anti-androgenic effects and prolactin levels rise.
8.Anticholinergics
Atropine, scopolamine, oxybutynin, etc. can cause erectile dysfunction when used in large doses. The mechanism is to inhibit acetylcholine, thus inhibiting the parasympathetic nervous system, so that the penis cannot be reflexively engorged with blood.
9.Proton pump inhibitor
The effect of omeprazole on male sexual function is twofold, which can cause both sustained erection and difficulty in erection, leading to penile erectile dysfunction. The average time of erectile dysfunction is 4 days after taking the drug, and can cause breast enlargement. The mechanism is to interfere with the function of the reproductive center and the humoral regulation of endocrine hormones in the reproductive system.
10.Dopamine receptor inhibitors
Metoclopramide and domperidone can block the hypothalamic-pituitary dopamine pathway, which increases prolactin secretion and leads to breast enlargement.
11.Antipyretic and analgesic drugs
The mechanism is to inhibit the synthesis of prostaglandins and affect the quality of semen, resulting in less sperm or azoospermia. The use of indomethacin, diclofenac sodium and naproxen in women during the ovulation phase of the menstrual cycle can inhibit ovulation, mainly by preventing the rupture of normally developing ovarian follicles. Therefore, women who are preparing to become pregnant should avoid the use of these NSAIDs during ovulation.
12.Prednisone drugs
The long-term use of digitalis and digoxin can lead to male hypogonadism and breast development, the mechanism of which may be similar to the chemical structure of hormones, and the competitive inhibition effect.
13.Anti-arrhythmic drugs
Amiodarone, propyzamide, mexilate, propafenone, and pranolol can cause decreased libido and penile erection disorder.
14.Anti-bacterial drugs
Tetracycline, neomycin, furan drugs, etc. have toxic effects on the gonads. Ketoconazole, bifenbendazole, metronidazole and ashwagandha, cefazolin sodium, isoniazid, ethambutol, etc. can lead to sexual dysfunction.
15.Anti-psychotic drugs
Promethazine, proepidone, methiodiazine, sulpiride and other drugs can cause reduced testosterone production, decreased libido, erectile dysfunction and gynecomastia by affecting the secretion of pituitary gonadotropins. Lithium carbonate can cause penile erectile dysfunction and is associated with the inhibition of central dopaminergic neurotransmission. Benzodiazepines chlorofluorocarbon, chlorazepine due to the central inhibitory neurotransmitter γ-aminobutyric acid to strengthen or ease the effect, often cause sexual dysfunction.
16.Other
Lyuzosulfapyridine treatment of chronic inflammatory bowel disease can cause oligospermia and infertility. The main manifestations are reduced sperm motility, abnormal morphology and decreased density, etc. This effect may be the effect of sulfasalazine structure in salazosulfapyridine. Fat emulsions, protein inhibitors, phenytoin sodium, carbamazepine, heparin, ketamine, cycloheximide, cocaine, cannabis, lamivudine, amphetamines, isotretinoin, and the Chinese herbs Zang Yin Chen and Lei Gong Dong have all been reported to cause sexual dysfunction and should be noted when used clinically.
In summary, there is a wide range of drugs that cause reproductive function impairment, with different mechanisms of action. Regular therapeutic doses can lead to pharmacogenic reproductive impairment and sexual dysfunction, so it should be highly valued by clinicians and pharmacists in order to guide patients to use drugs safely and effectively. Patients should also be aware of this when using medication! Especially in the case of excessive dosage! Be sure to pay close attention!