Men's Health: The Effects of Diuretics and Common Antihypertensive Drugs on Sexual Function and Coping Strategies

Antihypertensive Drugs

1. Guanethidine

Guanethidine is a synthetic guanidine antihypertensive drug and a representative adrenergic neuron blocking agent. In retrograde ejaculation caused by abnormal nerve innervation, guanethidine induces a so-called chemical sympathectomy effect.

Guanethidine has a strong and sustained antihypertensive effect, dilating both resistance and volumetric blood vessels, slowing the heart rate, leading to decreased peripheral resistance, reduced venous return, and decreased cardiac output. It also has a strong antihypertensive effect. Guanethidine antagonizes adrenergic mediators, a characteristic that has been clinically reported. Its main effect on sexual function is the inhibition of ejaculation in men, the degree of which is often related to the dosage. For example, at daily doses above 25 mg, approximately 50%–60% of male patients may experience delayed or absent ejaculation. Guanethidine can persistently inhibit the release of neurotransmitters from adrenergic neurons, significantly reducing norepinephrine levels, which may cause erectile dysfunction in patients with hypertension, a fact confirmed by clinical observations. A small number of men taking this drug do experience erectile dysfunction. In a group of 22 male patients taking guanethidine and chlorothiazide diuretics to control blood pressure, 3 (13.6%) experienced impotence, and another 13 (59.1%) experienced decreased libido. Its mechanism of action likely reflects the drug's inhibitory effect on sexual response, or perhaps psychological factors are simply influencing ejaculatory dysfunction. Pretchard et al. (1986) reported that guanethidine caused erectile dysfunction in 40%–67% of cases and ejaculatory dysfunction in 40%–70%.

Among antisympathetic drugs, guanethidine is more likely to cause impotence than clonidine, which may be related to the fact that guanethidine cannot enter the central nervous system and mainly exerts its effects peripherally.

2. Hydralazine
Hydralazine directly dilates small arteries, reducing peripheral vascular resistance and lowering blood pressure, with a greater reduction in diastolic pressure than systolic pressure. This antihypertensive effect is a result of the drug directly relaxing the smooth muscle of small arteries, and generally does not cause sexual dysfunction except at very high doses. However, when the daily dose exceeds 200 mg, approximately 5%–10% of male patients experience decreased libido, sometimes accompanied by impotence. This disturbance of libido and sexual function is now considered to be caused by an effect similar to systemic lupus erythematosus (SLE). This syndrome is only likely to occur at daily doses exceeding 400 mg of hydralazine. The impact of SLE on sexual function varies from person to person. Like patients with other chronic diseases with many symptoms, libido may be significantly reduced, and vaginal lubrication may be weakened. Some believe this may also be related to vitamin B₆ deficiency caused by the drug.

3. Thiazides (Thiazides)
Thiazides are medium-potency oral diuretics widely used clinically. The first synthesized dichlorothiazide had strong diuretic and natriuretic effects. Many new derivatives have been synthesized since then, including commonly used ones such as hydrochlorothiazide, trichlorothiazide, cyclopentylchlorothiazide, benzylfluorothiazide, and methaqualizide. Thiazides have a direct effect on the kidneys, acting on the cortical portion of the thick ascending limb of the loop of Henle, inhibiting the active reabsorption of chloride ions and the passive reabsorption of sodium ions in this region, thus promoting urination. Long-term use can lead to hypokalemia and a slight increase in HCO3- excretion. Due to sodium excretion and diuresis, a moderate negative sodium and water balance is created, reducing extracellular fluid and intravascular blood volume, thereby lowering blood pressure.

Because thiazide diuretics are often used as a basic antihypertensive drug in combination with other antihypertensive drugs, observing and analyzing the effects of these drugs on sexual function becomes quite complex. However, clinical observation data shows that approximately 5% of male patients taking thiazide diuretics long-term may experience drug-induced sexual dysfunction. Thiazide diuretics can worsen the severity of sexual dysfunction in diabetic patients, and special attention should be paid to their clinical application.

4. Furosemide
Furosemide (furosemine, diuretic sulfonamide, furosemide) is a highly potent diuretic. It has high diuretic efficacy and rapid action, promoting the release of renin, leading to extracellular hypochloremia and metabolic alkalosis. Long-term use has been observed in 5% of male patients with erectile dysfunction. Some believe that the sexual dysfunction is caused by hyperglycemia and hypokalemia resulting from the use of these highly potent diuretics. Clinically, it has also been observed that sexual dysfunction caused by diuretic-induced hypokalemia can be rapidly improved by potassium supplementation (potassium chloride).

5. Spironolactone (Aldactone) is a synthetic aldosterone antagonist. Its chemical structure is similar to aldosterone (both have a steroid nucleus as their basic structure). Spironolactone is a weak diuretic (low-potency diuretic), also known as a potassium-sparing diuretic due to its potassium-retention and sodium-excretion effects. This drug can cause decreased libido, impotence, and gynecomastia in men. In women, it can cause menstrual irregularities and breast tenderness. These effects are dose-dependent; for example, patients rarely experience these sexual problems at daily doses of 100 mg or less. However, at doses exceeding 100 mg, these symptoms are more likely to occur. Studies have shown that after healthy young men received 400mg of spironolactone daily, approximately 67% developed gynecomastia (male pattern gynecomastia) within 24 weeks; 22% experienced decreased libido; and semen characteristics also changed. These sexual dysfunction symptoms resolved rapidly upon discontinuation of the medication.

Spiconolactone exhibits significant progesterone activity, which may be one reason why it causes decreased libido, as progesterone is generally considered a sex depressant.

For all antihypertensive drugs, the most frequently reported reaction is impotence, followed by decreased libido. Guanethidine is an exception; compared to other drugs, it significantly causes more ejaculatory dysfunction. Guanethidine is the drug most commonly associated with sexual reactions, with over 10% of users discontinuing the medication due to potential sexual reactions. Discontinuation due to sexual reactions is also common with chlorthalidone, methyldopa, and reserpine, but this type of reaction is less common with spironolactone. Only six female patients discontinued medication due to sexual dysfunction.

Most antihypertensive drugs affect sexual function to varying degrees, and are now considered, along with antipsychotics, to be among the most likely to cause sexual dysfunction. The distress experienced by hypertensive patients due to drug side effects (especially related to sexual function) sometimes seems to outweigh the hypertension itself.