Male sexual function, from arousal to ejaculation, involves a complex interplay of psychogenic, neurogenic, vascular, and endocrine factors. Disruptions in any of these processes can lead to male sexual dysfunction.

 

Ejaculation vs orgasm

 

Despite happening simultaneously, male ejaculation and orgasm are two completely separate phenomena.

Revenig L, Leung A, Hsiao W. Ejaculatory physiology and pathophysiology: assessment and treatment in male infertility. Transl Androl Urol. 2014;3(1):41–49.

Ejaculation is a purely physical—controlled by the autonomic nervous system—involving the emission and expulsion of seminal fluid. On the other hand, an orgasm is governed by the central nervous system and involves a mentally and emotionally intense state experienced at the climax of sexual arousal.

 

PET studies show brain activity during orgasm in the deep mesodiencephalic transition zones and cerebellum, with reduced activity in the medial temporal lobe and amygdala.

Belladelli F, Pozzi E, Fallara G, et al. Orgasm and ejaculation disorders. In: Bettocchi C, Busetto GM, Carrieri G, et al. (eds). Practical Clinical Andrology. Springer, Cham; 2023;75–87.

Furthermore, dopamine and norepinephrine excite the prefrontal cortex, enhancing orgasms, while serotonin inhibits it, reducing orgasm intensity. Drugs affecting these neurotransmitters can influence orgasm.

Saffati G, Naeem T, Kaaki B, et al. First-time orgasm in a young man with lifelong anorgasmia after flibanserin use: a case report. Sex Med. 2024;11(6):qfad066.

 

 

 

Delayed orgasm and anorgasmia

 

A 2024 review from Nature Portfolio states, “Though it is acknowledged that ejaculation and orgasm are separate entities, the term DE is often used to refer to both difficulties with ejaculation and orgasm.”

Nguyen V, Dolendo I, Uloko M, et al. Male delayed orgasm and anorgasmia: a practical guide for sexual medicine providers. Int J Impot Res. 2024;36(3):186–193.

 

The central nervous system's involvement makes DO and AO multifactorial. The ICD-11 states that anorgasmia is “the absence or marked infrequency of the orgasm experience or markedly diminished intensity of orgasmic sensations. The pattern of absence, delay, or diminished frequency or intensity of orgasm occurs despite adequate sexual stimulation, including the desire for sexual activity and orgasm, has occurred episodically or persistently over at least several months, and is associated with clinically significant distress.”

Shindel AW, Althof SE, Carrier S, et al. Disorders of Ejaculation: An AUA/SMSNA Guideline (2020). J Urol. 2022;207(3):504–512.

 

The American Urology Association (AUA) condensed the definition of anorgasmia as “the condition in which sexual climax cannot be reached via any means of stimulation.”

Shindel AW, Althof SE, Carrier S, et al. Disorders of Ejaculation: An AUA/SMSNA Guideline (2020). J Urol. 2022;207(3):504–512.

 

 

 

Pathophysiology

 

Endocrine and metabolic dysfunction

Testosterone affects desire, erection, and ejaculation through brain receptors and penile pathways.

Bianchi N, Prontera O, Dicuio M, et al. Male sex hormones in andrology today. In: Bettocchi C, Busetto GM, Carrieri G, et al. (eds). Practical Clinical Andrology. Springer, Cham; 2023;251–261.

Thyroid hormones regulate ejaculation, prolactin influences sexual desire via serotonin and dopamine, and estrogens affect desire.

 

• The review from the International Journal of Impotence Research found lower testosterone levels (p < 0.05) in patients with DO and premature ejaculation (PE), with testosterone deficiency more common in DO.

  Nguyen V, Dolendo I, Uloko M, et al. Male delayed orgasm and anorgasmia: a practical guide for sexual medicine providers. Int J Impot Res. 2024;36(3):186–193.

   

• The International Journal of Andrology reports a progressive rise in prolactin and thyroid-stimulating hormone (TSH) levels in men with PE and DO and a progressive fall in total testosterone.

  Corona G, Jannini EA, Lotti F, et al. Premature and delayed ejaculation: two ends of a single continuum influenced by hormonal milieu. Int J Androl. 2011;34(1):41–48.

   

• In a 2023 retrospective case-control study of 11,602 men with DE, a majority of cases were associated with metabolic syndrome.

  Mulloy E, Zhang A, Balladelli F, et al. Diagnoses and medications associated with delayed ejaculation. Sex Med. 2023;11(4):qfad040.

   

Medications

SSRIs, antipsychotics, and opioids are common causes of drug-induced DO. Escitalopram causes DO in 30% of users after 8 weeks; with bupropion, the rate is 15%.

Nguyen V, Dolendo I, Uloko M, et al. Male delayed orgasm and anorgasmia: a practical guide for sexual medicine providers. Int J Impot Res. 2024;36(3):186–193.

 

Psychological distress

Psychogenic DO stems from stress, anxiety, hostility, and relationship issues. A 2023 survey of 351 men with DO found anxiety and stress as primary causes in 41%.

Rowland DL, Padilla S, Kӧvi Z, et al. Self-reported reasons for having difficulty reaching orgasm in men with diverse etiologies. Sex Med. 2023;11(3):qfad030.

 

Other noteworthy causes include penile hyperstimulation and post-pelvic surgery nerve damage.

Nguyen V, Dolendo I, Uloko M, et al. Male delayed orgasm and anorgasmia: a practical guide for sexual medicine providers. Int J Impot Res. 2024;36(3):186–193.

 

 

Treatment strategies

 

There is no FDA-approved treatment for anorgasmia, but secondary anorgasmia often improves once the underlying cause is addressed. There are various options for management.

Sex therapy

Sex therapy is recommended for all patients with DO or AO, including couples therapy, cognitive-behavioral therapy, and mindfulness techniques.

Management of underlying cause

Short-acting intranasal testosterone, administered 60 minutes before sexual activity, can help treat anorgasmia but is only indicated for men with clinically diagnosed testosterone deficiency. Endocrine referral is necessary for other hormonal disorders like thyroid issues and hyperprolactinemia.

Nguyen V, Dolendo I, Uloko M, et al. Male delayed orgasm and anorgasmia: a practical guide for sexual medicine providers. Int J Impot Res. 2024;36(3):186–193.

 

Medication adjustments

Adjusting SSRI or other medication regimens may alleviate DO symptoms.

Shindel AW, Althof SE, Carrier S, et al. Disorders of Ejaculation: An AUA/SMSNA Guideline (2020). J Urol. 2022;207(3):504–512.

The AUA recommends adjunctive therapies like bethanecol and cyproheptadine or substituting SSRIs/TCAs with alternatives like bupropion or buspirone.

 

Pharmacotherapy

No FDA-approved drugs for DO exist, but options include bupropion, cabergoline, bethanecol, and oxytocin.

Shindel AW, Althof SE, Carrier S, et al. Disorders of Ejaculation: An AUA/SMSNA Guideline (2020). J Urol. 2022;207(3):504–512.

 

• Bupropion, an atypical antidepressant, has lower sexual side effects and may improve satisfaction, as shown in a randomized trial of 10 men with DO.

  Shindel AW, Althof SE, Carrier S, et al. Disorders of Ejaculation: An AUA/SMSNA Guideline (2020). J Urol. 2022;207(3):504–512.

   

• Cabergoline, a dopamine agonist, can reduce prolactin levels and was found to enhance sexual function in 66% of patients with DO in a case series of 131 men.

  Shindel AW, Althof SE, Carrier S, et al. Disorders of Ejaculation: An AUA/SMSNA Guideline (2020). J Urol. 2022;207(3):504–512.

   

• Recently, a 2023 case report highlighted the success of flibanserin—an FDA-approved therapy for hypoactive sexual desire in premenopausal women—in treating a 28-year-old male with treatment-resistant primary anorgasmia.

  Saffati G, Naeem T, Kaaki B, et al. First-time orgasm in a young man with lifelong anorgasmia after flibanserin use: a case report. Sex Med. 2024;11(6):qfad066.

  Flibanserin increases dopamine and norepinephrine, and it reduces serotonin in the prefrontal cortex, improving orgasms.

   

• Authors publishing in Practical Clinical Andrology state that penile vibratory stimulation (PVS) can stimulate the dorsal penile nerve and improve orgasms in 32%–96% of the patients.

  Belladelli F, Pozzi E, Fallara G, et al. Orgasm and ejaculation disorders. In: Bettocchi C, Busetto GM, Carrieri G, et al. (eds). Practical Clinical Andrology. Springer, Cham; 2023;75–87.