CME INDIA Presentation by Dr. Brij Mohan, MD, FICP, FIACM, Fellow Diabetes India, Consultant physician, Kanpur, India.

Based on a presentation at ICDM conference, Vadodara 2023.

Sexual health inquiry is very important aspect of Comprehensive Diabetes Care

• Diabetes is associated very strongly with sexual problems in Both men & women.
• Diabetes has numerous end organ effects and exerts psychological toll & these two may predispose diabetics to sexual problems.
• Sexual problems fall into 4 Domains: Problems Related to Sexual Desire, Arousal, Orgasm and Pain associated with sexual activity.
• Causes of sexual dysfunction may be complex due to Psychological, Biomedical Socio-cultural and Interpersonal factors.
• Erectile Dysfunction (ED) is common in men with Diabetes; other than ED, Ejaculatory Dysfunction and Sexual Desire issues may also occur.

How common is the problem?

Risk factors are many

Different Types of Sexual Dysfunctions in Men and Women

Sexual dysfunction only in Men:

• Erectile Dysfunction
• Delayed Ejaculation
• Premature Ejaculation

Sexual dysfunction only in Women:

• Lubrication problems
• Dyspareunia
• Recurrent Perineal Infections

Sexual dysfunction common in Men and Women Both:

• Sexual Aversion
• Decreased sexual desire
• Decreased emotional arousal
• Orgasmic Dysfunction
• Pain during contact

Erectile Dysfunction [ED] in Diabetes

• Erectile dysfunction (ED) is defined as inability to achieve or maintain an erection to complete sexual intercourse or another chosen sexual activity sufficiently.
• The pathophysiology of ED in DM is multifactorial
• It can be Psychological or Organic.
• Organic ED can be due to following reasons:
  • Vascular – Impaired relaxation of cavernosal smooth muscle due to endothelial derived nitric oxide due to glycosylation products
  • Neurological – Neuropathy – Involves Autononomic & Somatic nerves essential to erections
  • Hormonal – Low testosterone levels – Hypogonadism in diabetic men may be secondary to decline in of pituitary hormones responsible for stimulating testicular production of testosterone.

• Low levels of testosterone may lead to a decline in sexual desire.

Hypogonadism in DM

• Diabetic men may be checked for Serum Total Testosterone; Sex Hormone Binding Globulin & Albumin to see free & bioavailable testosterone
• Many labs offer a “Testosterone Panel” that includes all relevant factors.

• Testing should be done between 8 AM and 11 AM when Testosterone is highest.
• Cut-off values for “LOW” testosterone are controversial.
• Symptoms of hypogonadism are more common in men with total testosterone levels < 320 ng/dL and free testosterone levels < 64 pg/mL.
• When assessing a single report of low testosterone, providers should consider confirmatory testing to include repeat testosterone as well as pituitary hormones (FSH, LH and Prolactin) to rule out central causes of hypogonadism.
• Patients with Low Testosterone + Symptoms (Decreased Libido, ED, Fatigue, Decreased Bone Mineral Density, Depressed Mood etc) in which no other causes are apparent, should be considered for Testosterone Replacement.

How it happens?

Interesting data on board

Diagnostic Test for ED

1. Nocturnal Penile Tumescence and Rigidity Testing;
2. Intracavernosal injection (ICI);
3. Penile duplex ultrasound;
4. Cavernosometry;
5. Selective internal pudendal angiography

• Clinicians should counsel men with ED who have comorbidities that lifestyle modifications, [changes in diet and increased physical activity] improve overall health and may improve erectile function. (Moderate Recommendation; Evidence Level: Grade C)

Erectile Dysfunction: Treatment approach

Non-pharmacological approach

• Lifestyle changes
• Behavioral therapies
• Supportive therapies
• Self-help techniques
• Extensive retraining program
• Mechanical Aids

Pharmacological approach

• Oral therapies
• Injectables
• Devises
• Surgery

Pharmacological Approach for Erectile Dysfunction

Courtesy: https://uroweb.org/guidelines/sexual-and-reproductive-health/chapter/management-of-erectile-dysfunction

PDE5Is are the first-line treatment for erectile dysfunction

• As in 2023, four PDE5I drugs have been approved by the FDA, namely sildenafil, tadalafil, vardenafil, and avanafil.
• These PDE5Is have different pharmacokinetic properties but have similar efficacy, safety, and tolerability.
• During treatment, adverse reactions such as headache, blush, dyspepsia, and visual disturbance can occur

Appropriate Use of PDE5 Inhibitors

Penile Attack is not a Myth

Mindfulness is Must

Which OHA to Use?

Alternative Medicine for ED

• Panax Ginseng
• Pygnogenol
• Prelox (Combination of Pygnogenol®, L-arginine, L-citrulline and roburins)
• Tribulus Terrestris
• Lepidium Meyenii
• L-arginine

L – Arginine in ED

• Daily use of L-arginine 5 g with tadalafil 10 mg significantly increased the International Index of Erectile Function scores and total testosterone levels as compared to each drug alone in diabetic patients with erectile dysfunction.(Ref-5)

Natural Polyphenols in ED

• Administration of Pycnogenol leads in improvement of erectile function in patients with ED and diabetes (DM group) by 45 %, in NDM group by 22 %, in lowering of total-, LDL-cholesterol by 20 % and 21 % and glycaemia by 22 % in DM.(Ref-6)

Wisdom Pearls

• Screen all adults with diabetes with “sexual history.”
• Message is CLEAR: Sexual HEALING IN “DIABETES clinics.”

CME INDIA Tail-Piece:

Courtesy: Wang CM, Wu BR, Xiang P, Xiao J, Hu XC. Management of male erectile dysfunction: From the past to the future. Front Endocrinol (Lausanne). 2023

Which PDE5 inhibitors?

Various PDE5 inhibitors, such as sildenafil, tadalafil, udenafil and vardenafil, have shown efficacy rates as high as 80% in ED patients, associated with comorbidities.

Avanafil is superior to sildenafil?

• It has been found that Avanafil is superior in improving the International Index of Erectile Function – Erectile Function domain score at the end of 12 weeks of treatment with the added advantage of faster onset of action. (7)
• It is a second-generation selective PDE5 inhibitor, has a rapid onset of action (as early as 15 min), a Tmax of 30–45 min and a terminal half-life of 3–5 h. The recommended starting dose of avanafil is 100 mg taken as early as approximately 15 min before sexual activity, on an as needed basis, and based on efficacy and/or tolerability, the dose can be increased to 200 mg taken as early as approximately 15 min before sexual activity, or decreased to 50 mg taken approximately 30 min before sexual activity.
• Avanafil is also advantageous in terms of side-effects due to its high selectivity for PDE5.
• Avanafil has relatively little cross-reactivity with other PDE isoenzymes, especially PDE1, PDE6 and PDE11, which are causes of various side-effects (PDE1 isozyme affects vascular smooth muscle contraction and its inhibition leads to vasodilation and symptomatic hypotension, headache and flushing.)
• It has been found that avanafil 200 mg has the lowest rate of common adverse events in terms of headache (9.3% vs sildenafil 100 mg 12.8% vs tadalafil 20 mg 14.5% and vs vardenafil 20 mg 16%), flushing (3.7% vs sildenafil 100 mg 10.4% vs tadalafil 20 mg 4.1% and vardenafil 20 mg 12%), abnormal vision (none vs sildenafil 100 mg 1.9% and vardenafil 20 mg <2%) and back pain/myalgia (<2% vs tadalafil 6.5%/5.7%) (Ref-7)

References:

1. Burnett AL, Nehra A, Breau RH, Culkin DJ, Faraday MM, et al. Erectile Dysfunction. American Urological Association. Available at https://www.auanet.org/guidelines/male-sexual-dysfunction-erectile-dysfunction-(2018). 2018;
2. https://uroweb.org/guidelines/sexual-and-reproductive-health/chapter/management-of-erectile-dysfunction
3. Kim S, Cho MC, Cho SY, Chung H, Rajasekaran MR. Novel Emerging Therapies for Erectile Dysfunction. World J Mens Health. 2021 Jan;39(1):48-64. doi: 10.5534/wjmh.200007. Epub 2020 Mar 16. PMID: 32202086; PMCID: PMC7752520.
4. Wang CM, Wu BR, Xiang P, Xiao J, Hu XC. Management of male erectile dysfunction: From the past to the future. Front Endocrinol (Lausanne). 2023 Feb 27;14:1148834. doi: 10.3389/fendo.2023.1148834. PMID: 36923224; PMCID: PMC10008940.
5. El Taieb M, Hegazy E, Ibrahim A. Daily Oral l-Arginine Plus Tadalafil in Diabetic Patients with Erectile Dysfunction: A Double-Blinded, Randomized, Controlled Clinical Trial. J Sex Med. 2019 Sep;16(9):1390-1397. doi: 10.1016/j.jsxm.2019.06.009. Epub 2019 Jul 17. PMID: 31326304.
6. Trebaticky B, Muchova J, Ziaran S, Bujdak P, Breza J, Durackova Z. Natural polyphenols improve erectile function and lipid profile in patients suffering from erectile dysfunction. Bratisl Lek Listy. 2019;120(12):941-944. doi: 10.4149/BLL_2019_158. PMID: 31855055.
7. Boeri L, Capogrosso P, Ventimiglia E et al. Avanafil – a further step to tailoring patient needs and expectations. Expert Rev. Clin. Pharmacol. 2016; 9: 1171–81.

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