Can Fluoxetine or Spironolactone Cause Low Libido?
Yes, both fluoxetine and spironolactone reliably cause decreased libido, with spironolactone causing this side effect in more than 10% of patients through its anti-androgenic properties, and fluoxetine causing sexual dysfunction including decreased libido in 34-58% of patients through serotonergic mechanisms. 1, 2, 3
Spironolactone and Low Libido
Spironolactone consistently causes decreased libido as one of its most common side effects, occurring in more than 10% of treated patients. 4, 1, 2 This is a direct consequence of its anti-androgenic mechanism of action rather than an idiosyncratic reaction.
Mechanism and Clinical Impact in Both Sexes
In men, spironolactone decreases testosterone production and competitively inhibits testosterone and dihydrotestosterone binding to androgen receptors, resulting in decreased libido, gynecomastia, impotence, and decreased sexual function. 1, 2
In women, spironolactone causes menstrual irregularities, decreased arousal, and sexual dysfunction including decreased libido. 1, 2, 5
The sexual side effects can significantly impair quality of life and may not reverse immediately upon discontinuation of the medication. 1
Clinical Considerations for Spironolactone
The European Society of Cardiology recommends considering alternative treatments in patients with pre-existing sexual dysfunction, as spironolactone caused gynecomastia in 10% of men in the RALES trial. 2
Alternative diuretics such as hydrochlorothiazide or chlorthalidone lack anti-androgenic effects and should be considered when sexual function is a concern. 2
Fluoxetine and Low Libido
Fluoxetine causes sexual dysfunction including decreased libido in a substantial proportion of patients, with rates varying from 34% to 58% depending on whether patients are directly questioned versus spontaneously reporting symptoms. 4, 6, 3
Incidence and Spectrum of Sexual Dysfunction
When physicians directly ask about sexual side effects, 58% of patients report sexual dysfunction with SSRIs, compared to only 14% when spontaneously reported. 7
In a prospective study of 160 fluoxetine-treated patients, 34% reported new-onset sexual dysfunction: 10% reported decreased libido alone, 13% reported decreased sexual response alone, and 11% reported declines in both areas. 3
The FDA label for fluoxetine acknowledges sexual dysfunction as a treatment-emergent adverse event, though specific rates for decreased libido are grouped with other sexual side effects. 6
Mechanism and Clinical Characteristics
SSRIs cause sexual dysfunction through multiple mechanisms including effects on serotonin and dopamine reuptake, induction of prolactin release, anticholinergic effects, and inhibition of nitric oxide synthetase. 8
Sexual side effects are strongly dose-related, with higher doses associated with increased frequency of erectile dysfunction and decreased libido. 4, 8, 7
Men show higher incidence of sexual dysfunction than women, but women's sexual dysfunction tends to be more intense. 7
Critical Pitfall: Persistence After Discontinuation
A critical and often overlooked issue is that SSRI-induced sexual dysfunction, including decreased libido, can persist long-term after discontinuation in some patients. 9 Case reports document permanent erectile dysfunction, loss of libido, and genital anesthesia persisting months to years after stopping fluoxetine and other SSRIs, with no psychological causes or common medical causes identified. 9
Comparative Considerations
Among SSRIs, paroxetine shows the highest rates of sexual dysfunction, causing more delay of orgasm/ejaculation and impotence than fluoxetine, sertraline, or fluvoxamine. 4, 1, 7
Only 5.8% of patients with SSRI-induced sexual dysfunction experience complete resolution within 6 months of continued treatment, while 81.4% show no improvement at all. 7
In contrast to the negative effects, the American Urological Association notes that SSRIs including fluoxetine at doses of 5-60 mg daily are effective for treating premature ejaculation, with some patients preferring to maintain the delayed ejaculation effect. 4, 7
Management Approach
For spironolactone: Consider alternative diuretics (hydrochlorothiazide, chlorthalidone) or aldosterone antagonists without anti-androgenic effects (eplerenone) when sexual function is a priority. 2
For fluoxetine: Dose reduction may help as effects are dose-related, though 81.4% of patients show no improvement in sexual function even after 6 months. 8, 7
Switching from SSRIs to medications with different mechanisms (moclobemide, amineptine, or bupropion) resulted in improvement in sexual function in small studies. 8, 7