Is 2mg estradiol (estrogen) sublingual twice daily, 100mg spironolactone (aldosterone antagonist) daily, and 0.5mg dutasteride (5-alpha-reductase inhibitor) daily an appropriate dosing regimen for lowering libido and inducing sexual dysfunction?

This Regimen Is Not Appropriate for Your Stated Goal

The medication combination you describe—2mg estradiol sublingual twice daily, 100mg spironolactone daily, and 0.5mg dutasteride daily—is not designed or FDA-approved for intentionally lowering libido or causing sexual dysfunction, and using these medications for this purpose represents off-label use with significant safety concerns.

Critical Safety and Appropriateness Issues

Lack of Evidence-Based Support

• None of the medications in your regimen are approved or recommended in medical guidelines for the specific goal of reducing libido or inducing sexual dysfunction 1.
• The available evidence addresses these medications in entirely different clinical contexts: estradiol for hormone replacement in women with premature ovarian insufficiency 1, dutasteride for benign prostatic hyperplasia 1, 2, and spironolactone as an antiandrogen adjunct 3.

Concerning Adverse Effect Profile

Dutasteride carries significant warnings about persistent sexual dysfunction:

• The FDA label explicitly states that sexual adverse reactions (impotence, decreased libido, ejaculation disorders) "may persist after treatment discontinuation" and "the role of dutasteride in this persistence is unknown" 2.
• In clinical trials, dutasteride monotherapy at 0.5mg daily caused decreased libido in 3.1% during the first year, with impotence occurring in 4% of subjects 2.
• Your dose of 0.5mg daily matches the standard BPH treatment dose, but using it to intentionally cause dysfunction raises serious ethical and medical concerns 1, 2.

Estradiol at supraphysiologic doses poses cardiovascular and thrombotic risks:

• The 4mg daily total dose (2mg twice daily) you describe exceeds standard hormone replacement dosing of 1-2mg daily for women with premature ovarian insufficiency 1.
• High-dose estrogen therapy increases risks of venous thromboembolism and cardiovascular events, particularly without appropriate medical monitoring 1.

Spironolactone has limited efficacy for your stated goal:

• Research shows spironolactone at 100mg daily does not enhance testosterone suppression when combined with estradiol and may actually impair achievement of target estradiol levels 4.
• In the context you describe, spironolactone's antiandrogen effects are modest and do not reliably produce the sexual dysfunction you're seeking 3, 4.

Postmarketing Safety Concerns

• Dutasteride has postmarketing reports of depressed mood, testicular pain, and testicular swelling—adverse effects beyond the sexual dysfunction profile 2.
• The long-term safety of this medication combination for your stated purpose has never been studied 2.

Medical and Ethical Considerations

This medication regimen appears to be transgender hormone therapy being misused:

• The combination of estradiol, spironolactone, and a 5-alpha-reductase inhibitor is consistent with feminizing hormone therapy protocols 4.
• However, using these medications with the explicit goal of causing sexual dysfunction rather than gender affirmation represents a fundamental misapplication 4.

Alternative approaches exist for managing unwanted sexual urges:

• Selective serotonin reuptake inhibitors (SSRIs) such as paroxetine 20mg daily, sertraline 50-200mg daily, or fluoxetine 20-60mg daily have established efficacy for reducing libido as a known side effect 1.
• These medications are better studied for this application and have more predictable effects on sexual function 1.

Recommendation

You should not use this medication regimen for the purpose of lowering libido or causing sexual dysfunction. The combination lacks evidence-based support for this indication, carries significant risks including potentially irreversible sexual dysfunction, and may represent inappropriate use of medications designed for other purposes 2. If you are experiencing distressing sexual urges or compulsive sexual behavior, consultation with a psychiatrist or sexual medicine specialist would be appropriate to discuss evidence-based treatment options such as SSRIs, which have established safety profiles for this application 1.