AETIOLOGICAL CONSIDERATIONS IN SEXUAL DYSFUNCTIONS AND SEXUAL PAIN DISORDERS

1. Definition and nosology

Other sexual dysfunctions (ICD-11: HA40) — sexual dysfunctions (may involve desire, arousal, orgasm, pain areas) arising in the context of another physical illness, medication, substance, or mental disorder. Cases that do not fit specific HA01–HA20 categories or are comorbid.

Subtypes (ICD-11): a medical condition, injury, or the effects of surgery or radiation treatment (HA40.0); psychological or behavioural factors, including mental disorders (HA40.1); use of a psychoactive substance or medication (HA40.2); lack of knowledge or experience (HA40.3); relationship factors (HA40.4); cultural factors (HA40.5); other specified (HA40.Y).

2. History

• DSM-5 (2013) — formalization of “Substance/Medication-Induced Sexual Dysfunction”.
• 2000s — SSRIs-induced sexual dysfunction was widely described (Montejo A.L. studies).
• PSSD (Post-SSRI Sexual Dysfunction) — Bahrick A. (2008), EMA 2019 confirmation.

3. Epidemiology

• Sexual dysfunction with SSRI use 30–70%.
• ED in diabetic men 35–75%.
• High prevalence in cardiovascular diseases.
• Antipsychotic (especially risperidone, paliperidone) — due to hyperprolactinemia.

4. Aetiology and pathogenesis

• Medications: SSRI, SNRI, antipsychotics (D2 blockade, hyperprolactinemia), antihypertensive (beta-blocker, thiazide), opioids, 5-alpha reductase inhibitors (finasteride — suspected Post-Finasteride Syndrome), anticonvulsants.
• Substances: alcohol, opioids, chronic cannabis use, stimulants.
• Medical diseases: diabetes, cardiovascular, neurological (MS, Parkinson's disease, spinal trauma), endocrine (hypogonadism, hyperprolactinemia, thyroid), pelvic surgery and radiotherapy, chronic renal failure.
• Mental disorders: depression, anxiety, PTSD, schizophrenia.

5. Clinical features

• Decreased desire, excitement/erection dysfunction, anorgasmia, pain — etiology-dependent.
• Temporal relationship — onset with medication/substance.
• PSSD - persistent sexual dysfunction after SSRI discontinuation, genital numbness.

6. Diagnosis

6.1 Unified diagnostic criteria (DSM-5-TR)

A. Clinically significant sexual dysfunction symptomatology.

B. Evidence from history, physical examination, or laboratory results: symptoms are a direct consequence of medication, substance, or medical illness.

C. Distress.

6.2 Source-specific clarifications

• Montejo A.L. et al. — SSRI-induced dysfunction.
• EMA (2019) — included PSSD in SSRI label.

6.3 Diagnostic algorithm

1. Full medication and substance history.
2. Medical and endocrine assessment (testosterone, prolactin, glucose, HbA1c, lipids, thyroid).
3. Sexual function scales (FSFI, IIEF, ASEX).
4. Mental comorbidity screening.
5. Pelvic examination (in women).

6.4 Differential diagnosis

7. Examination and assessment

• Hormonal panel, glucose, lipids.
• FSFI, IIEF, ASEX (Arizona Sexual Experience Scale).
• Pelvic or urological examination when indicated.

8. Treatment

1. Etiological approach — first-line:
   • Medication-related — dose reduction, medication switch (bupropion, mirtazapine, vortioxetine, aripiprazole — in antidepressant or antipsychotic strategies);
   • Medical condition management (diabetes, hypertension, hypogonadism).
2. Adjunct pharmacotherapy — sildenafil (PDE5) in ED and SSRI-induced female dysfunction (Nurnberg JAMA 2008); bupropion adjunct.
3. In hyperprolactinemia — antipsychotic switch (aripiprazole, quetiapine) or dose modification; dopamine agonist only with endocrine assistance.
4. Psychotherapy and couple therapy — in psychogenic component.
5. Patient education and informed consent — prior to initiating antidepressants and antipsychotics, it is important to provide information about sexual side effects.
6. PSSD — no specific validated treatment exists; clinical support and monitoring; research ongoing.

Source-specific specifications

• Montejo A.L. et al. — antidepressant sexual side effect algorithms.
• EMA 2019 — PSSD risk information.
• NICE and APA guidelines — management of antidepressant sexual side effects.

Treatment methods

1. Medication Switch — SSRI → bupropion/mirtazapine/vortioxetine; risperidone → aripiprazole.
2. Sildenafil Adjunct — SSRI-induced dysfunction (male and female); Nurnberg JAMA RCT.
3. Bupropion Adjunct — In desire and orgasm disorders.
4. Antipsychotic Switch (aripiprazole) — In case of hyperprolactinemia.
5. Patient Education — Informed consent; discussing long-term risk.

9. Prognosis

Most cases improve with etiological management and medication switch; PSSD may rarely persist.

10. Myths and misconceptions

Myth 1: “Antidepressant sexual side effects are ‘temporary’ and require no intervention”

Evidence: Montejo studies — side effects are persistent (30–70%); require active management.

Myth 2: “PSSD is not a clinical entity”

Evidence: EMA 2019 — PSSD risk included in SSRI label; clinically recognized entity.

Myth 3: “Antipsychotic sexual dysfunction is the same for everyone”

Evidence: risperidone and paliperidone high hyperprolactinemia risk; aripiprazole and quetiapine less; switching is effective.

Myth 4: “Sexual dysfunction due to a medical illness is only a consequence of the illness, no intervention exists”

Evidence: In diabetic ED, PDE5 inhibitors are effective; sexual function improves with cardiovascular rehabilitation; active intervention is important.

Myth 5: “It is not necessary to discuss sexual side effects before starting an antidepressant”

Evidence: informed consent is ethical and clinical requirement; later emerging side effects lead to patient distrust and reduced treatment adherence.

11. Sources

1. WHO. ICD-11. HA40 Aetiological considerations in sexual dysfunctions and sexual pain disorders. 2024.
2. APA. DSM-5-TR. 2022.
3. Montejo A.L., Llorca G., Izquierdo J.A., Rico-Villademoros F. Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients. J Clin Psychiatry 2001;62(Suppl 3):10–21.
4. EMA. PRAC recommends new product information warnings on sexual dysfunction after SSRI/SNRI treatment. 2019.
5. Nurnberg H.G. et al. Sildenafil treatment of women with antidepressant-associated sexual dysfunction. JAMA 2008;300(4):395–404.
6. Bahrick A.S. Persistence of sexual dysfunction side effects after discontinuation of antidepressant medications. Open Psychol J 2008;1:42–50.