Treatment Plan: Anhedonia + Total Loss of Libido + Loss of Penile Sensation

Step 1 - Establish the Underlying Cause (Before Any Treatment)

Step 2 - Baseline Investigations

• Serum testosterone (8-10 AM, on at least 2-3 occasions) - hypogonadism threshold: <8 nmol/L (231 ng/dL)
• Serum prolactin - elevated levels suggest prolactinoma or drug effect
• LH and FSH - to classify hypogonadism as primary (testicular) vs. secondary (hypothalamic-pituitary)
• HbA1c and fasting glucose - diabetic neuropathy can ablate penile sensation
• Lipid profile, renal and liver function
• Thyroid function (TSH)
• Complete drug history - including prior SSRI, antipsychotic, finasteride, or antiandrogen use
• Neurologic testing if sensory loss is prominent: biothesiometry (graded vibratory perception), somatosensory-evoked potentials
• Psychological screening: PHQ-9, IIEF (International Index of Erectile Function)

Step 3 - Treat the Underlying Cause

A. If MDD / Depression is Driving Anhedonia + Low Libido

• Anhedonia and libido loss are core features of depression; successful antidepressant treatment can restore both.
• Preferred agents (least sexual side effects):
  • Bupropion (norepinephrine-dopamine reuptake inhibitor) - active on dopaminergic reward pathways, improves anhedonia, low sexual dysfunction burden; can also be added to an existing SSRI as an "antidote"
  • Mirtazapine (5-HT2 antagonist + α2 antagonist) - relieves orgasmic dysfunction; less libido-impairing than SSRIs
  • Agomelatine (melatonin receptor agonist + 5-HT2C antagonist) - evidence shows rapid improvement of anhedonia in MDD; favorable sexual side effect profile
• Avoid or switch away from SSRIs, SNRIs, TCAs, MAOIs, and lithium when sexual dysfunction is the primary complaint - these have the highest rates of desire and arousal impairment.
• If already on an SSRI: consider switching to bupropion or mirtazapine, or add bupropion 100-150 mg/day as augmentation.

B. If Hypogonadism is Confirmed (Testosterone <8 nmol/L)

• Testosterone Replacement Therapy (TRT) is the first-line treatment.
  • Indications: documented hypogonadism + symptoms consistent with testosterone deficiency (low libido, anhedonia-like low energy/mood, erectile dysfunction)
  • Testosterone consistently improves libido, mood, and energy in hypogonadal men; effects on anhedonia are mediated through mood improvement.
  • Forms: transdermal gel (daily), intramuscular injection (testosterone enantate 250 mg every 2-4 weeks), long-acting IM (testosterone undecanoate 1000 mg every 10-14 weeks)
  • Monitor: haematocrit, PSA, lipids, bone mineral density, and cardiovascular risk at follow-up.
  • Note: TRT is not useful when testosterone levels are already normal - it does not improve ED in eugonadal men and should be avoided in that setting.
• A 2024 Cochrane Review (PMID 38224135) confirmed that testosterone replacement in men with hypogonadism and sexual dysfunction significantly improves libido and sexual satisfaction.

C. If Hyperprolactinemia is Present

• Identify and stop any offending drug (antipsychotics, especially FGAs/risperidone, metoclopramide, TCA)
• If a prolactinoma is identified: dopamine agonists (cabergoline or bromocriptine) are the treatment of choice - they normalize prolactin, restore testosterone, and directly improve libido.
• If the cause is antipsychotic use and switching is not feasible: aripiprazole 5-10 mg/day added to the existing antipsychotic can normalize prolactin levels and restore sexual function through its partial D2 agonism.

D. For Loss of Penile Sensation Specifically

• Strict glycemic control (HbA1c target <7%)
• Alpha-lipoic acid 600 mg/day (antioxidant, evidence for peripheral neuropathy)
• Pregabalin or gabapentin for neuropathic pain if present
• Referral to endocrinology/neurology

• Genital numbness (anesthesia genitalis) is a hallmark of PSSD
• No universally effective treatment exists; documented options with partial evidence:
  • Bupropion (dopaminergic augmentation)
  • Buspirone (5-HT1A partial agonist)
  • Cyproheptadine 4-16 mg/day (5-HT2 antagonist) - may transiently reverse SSRI effects but causes sedation
  • Trial of PDE-5 inhibitors for local vascular and neurogenic effects
• PSSD may persist indefinitely; the patient and physician must be counseled accordingly.

• Discontinuation of 5α-reductase inhibitors; recovery may be slow or incomplete.

• Biothesiometry and penile Doppler to localize the deficit
• Pelvic floor physiotherapy
• Vacuum erection device (VED) to maintain penile oxygenation and neural tissue health

E. Adjunctive / Symptomatic Treatment for Sexual Function

Step 4 - Psychosexual and Lifestyle Interventions

• Sex therapy / CBT: addressing performance anxiety, which develops as a secondary reaction to any organic cause of ED; referral to a mental health professional improves treatment adherence.
• Lifestyle modifications counseled by Harrison's: weight loss, aerobic exercise, alcohol cessation, smoking cessation - all independently improve erectile function and mood.
• Relationship counseling: involving the sexual partner improves outcomes in anhedonia- and libido-related dysfunction.
• Validated questionnaires (IIEF, SHIM) to measure treatment response at follow-up.

Summary Algorithm

Anhedonia + Loss of Libido + Loss of Penile Sensation
            |
   Check testosterone (AM) + prolactin + drug history
            |
  ┌─────────┴──────────────────────────┐
  |                                    |
Low testosterone              Normal testosterone
  |                                    |
 TRT                       Look for depression (PHQ-9)
  + if prolactin high:           or PSSD / drug cause
  dopamine agonist                     |
                         ┌─────────────┴────────────┐
                         |                           |
                   MDD present              PSSD / drug-induced
                         |                           |
               Bupropion/Agomelatine       Switch/stop drug
               (avoid SSRIs)              + Bupropion/Buspirone
                         |
              Add PDE-5i for erectile/sensory symptoms
              + psychosexual therapy
              + lifestyle modification

• Harrison's Principles of Internal Medicine 22nd ed. (2025), pp. 3200-3202
• Kaplan & Sadock's Comprehensive Textbook of Psychiatry - Sexual Dysfunction ch. 33.17c
• Maudsley Prescribing Guidelines in Psychiatry, 15th ed., Table 1.46
• Cochrane Review: Testosterone replacement in men with sexual dysfunction (PMID 38224135, 2024)
• Lancet Healthy Longevity: Symptomatic benefits of testosterone by patient subgroups (PMID 37804846, 2023)