male sexual dysfunctions and treatments · •to present an overview of male sexual dysfunctions...
TRANSCRIPT
Male Sexual Dysfunctions and Treatments
Alexander W. Pastuszak, MD, PhDAssistant ProfessorDivision of Urology
Department of SurgeryUniversity of Utah School of Medicine
ISSM / SMSNA Sexual Health SymposiumNovember 24, 2019
Nairobi, Kenya
Disclosures
• Endo Pharmaceuticals – speaker, advisor, research / fellowship support
• Bayer AG – speaker
• Antares Pharmaceuticals – advisor
• Woven Health – founder and leadership position
Objectives• To present an overview of male sexual dysfunctions including
hypogonadism, erectile dysfunction, ejaculatory dysfunction, and Peyronie’s disease
• To discuss the role of testosterone in sexual function, and the diagnosis and management of hypogonadism (low testosterone)
• To examine ejaculatory dysfunction and its treatments
• To briefly discuss erectile dysfunction and (some) treatment
• To briefly present Peyronie’s disease
Hypogonadism
http://www.melbourneurology.net.au/patient-information/benign-prostate-enlargement-bph
Testosterone Has Critical Roles in Sexual Function
Testosterone’s Role in Sexual Function
• Testosterone is one of the main factors in male (and female) libido
• The chemical mechanism for normal erections is testosterone dependent• Men with low testosterone have a diminished response to
Viagra-like drugs
• Testosterone is likely important in regulating ejaculatory function
Definition of Clinical “Hypogonadism”
A disease complex of:
1. Low testosterone
(<300ng/dl)
2. Specific and non-
specific symptoms
Hypogonadal Symptoms
More Specific- Decreased libido
- Erectile dysfunction
- Delayed puberty
- Gynecomastia
- Breast tenderness
- Loss of axillary / pubic hair
- Small / shrinking testes
- Infertility
- Low bone mineral density
- Hot flushes / sweats
Less Specific- Low energy / motivation
- Decreased muscle strength
- Increased fat mass
- Depressed mood
- Poor concentration
- Poor memory
- Insomnia
- Decreased work
performance
J Clin Endocrinol Metab. 2010; 95:6.
Higher Centers
GnRHHypothalamus
Anterior
Pituitary
Sertoli Cells Leydig Cell
Germinal
Epithelium
FSH LH+ +
Inhibin
--
-
Male Hypothalamic-
Pituitary-Gonadal
Axis
Testosterone
Estrogen
Aromatase
Causes of Hypogonadism
Primary Hypogonadism- Testicular failure
- Cryptorchidism
- Bilateral torsion
- Orchitis
- Orchiectomy
- Klinefelter’s
- Chemotherapy
- Other toxins
Secondary Hypogonadism- Pituitary-hypothalamic injury
- Tumors
- Trauma
- Radiation
- Hemochromatosis
- Kallmann syndrome
- Inflammation
- Medications
- HIV/AIDS
- Obesity
Cause Unknown → Idiopathic Hypogonadism → 90% of cases
Incidence• 500,000 men diagnosed annually in the U.S.
Prevalence• Population-based studies (Europe and U.S.) → 2.1-12.8%
• Community-based studies (U.S.)→ 9.5-31.2%
• Few data beyond U.S. and Europe…
• Increases with age
• Varies with definition of hypogonadism
Journal of Hormones. 2014; http://dx.doi.org/10.1155/2014/190347.
N Engl J Med. 2004; 350:482.
Prevalence of Low Testosterone13.8 Million Men in the U.S.
Hypogonadism TreatmentTestosterone Therapy - Formulations• Transdermal gels / creams / patches
• Injections
• Subcutaneous pellets
• Intranasal gel
• Buccal
• (Orals)
Non-Testosterone Therapies• Human chorionic gonadotropin (HCG)
• Clomiphene citrate
• Anastrozole & other aromatase inhibitors
Benefits• Symptomatic Improvement
• Serum T levels
• Sexual function
• Bone / muscle mass
• Sleep
• Others
Risks• Erythrocytosis
• Infertility (when used alone)
• Testicular atrophy
• Local reactions
• Gynecomastia
• Cardiovascular risk(?)
Monitoring While on Therapy
Endocrine Society Recommendations• Initial evaluation 3-6 months after treatment initiation, then annually
• Baseline Hct, then at 3-6 months, then annually
• If elevated, stop T therapy until decreases or perform therapeutic
phlebotomy
• Repeat bone mineral density evaluation 1-2 years after therapy
initiation
• Men >40 years old with baseline PSA >0.6 ng/mL → DRE, PSA before
starting therapy, then at 3-6 months, then annually
J Clin Endocrinol Metab. 2010; 95: 2536.
Summary
• Hypogonadism affects many men
• Various definitions of hypogonadism exist, impacting diagnosis and treatment
• Treatment of hypogonadism primarily consists of testosterone therapy, though non-testosterone therapies are available
• Proper diagnosis and monitoring are essential during treatment
Ejaculatory Dysfunction
Ejaculation – The ProcessSeparate event from erection!
Thus, can occur in the ABSENCE of erection!
Sensory input - glans (S2-4)
(Dorsal Nerve)
Emission
Sympathetic input (T12-L1)
Periurethral muscle contraction
Vas deferens contraction
SV, prostate contraction
Bladder neck contraction
Bulbocavernosus / spongiosus
contraction
Projectile ejaculation
Expulsion
Somatic input (S1-3)
Transl Androl Urol. 2018; 7: 686.
Neurochemistry of Sexual Function
Effects of Sex Steroids in the Brain
Normal Hormonal FunctionTestosterone• AR ubiquitous → including pelvic floor
• High T = PE; Low T = DE in some men
• T levels vary in men with DE
Thyroid Hormone• Similar to T levels in effect → high thyroid = PE; low thyroid = DE
Prolactin
• May be surrogate of serotonergic activity• Suppressed during orgasm → spikes after (refractory period?)
• High Prl → low T and PE
Oxytocin
• Surges during ejaculation, orgasm, and detumescence
• Stimulates ejaculation, paternal nurturing, sexual desire, and long-term
romantic bonds
Other Determinants of Ejaculatory FunctionIELT Determinants: • Genetics
• Neurophysiology
• Behaviors
• Psychosocial variables
• Cultural influences
Somatic Considerations• Aging – decreased orgasm intensity
• Neurologic disorders (i.e. MS, DM)
• Endocrine disorders (i.e. T, Prl, thyroid)
• Medications
Premature Ejaculation (PE)Prevalence→ 3-75% due to DIFFERENCES IN DEFINITIONS
DSM-5 Definition• “The persistent or recurrent pattern of ejaculation occurring during
partnered sexual activity within about one minute following vaginal penetration and before the individual wishes it”
• Present in 75-100% of sexual encounters, causes distress, lasts at least 6 months, and can’t be explained by another disorder
Intravaginal Ejaculatory Latency Time (IELT)1,2
• Defined by 2 multinational population-based studies• Average → 5.7 minutes• Lifelong PE → mean IELT - 2 SD = ~1 minute• Acquired PE – ISSM Expert Consensus → IELT <3 minutes = PE
1. JAMA. 1999; 281: 537.
2. J Am Geriatr Soc. 2001; 49: 436.
Premature Ejaculation TreatmentFirst-Line Therapies• Daily SSRIs• On demand clomipramine, dapoxetine• Tramadol• Topical penile anesthetics
Other Therapies• Behavioral therapies
Alternative Therapies (Insufficient Evidence for Efficacy)• Testosterone therapy• Intracavernosal injection (ICI)• Oxytocin antagonists• Herbal medicines
Dapoxetine is the only
approved treatment for PE
Delayed Ejaculation (DE) / AnorgasmiaPrevalence → 1-4%3 – ALSO depends on DEFINITION USED
DSM-5 Definition
• The persistent or recurrent delay, difficulty, or absence of orgasm after sufficient sexual stimulation that causes personal distress
Intravaginal Ejaculatory Latency Time (IELT)1,2
• Normal (median) → 5.4 minutes (0.55-44.1 minutes)• DE → mean IELT + 2 SD = 22-25 minutes
1. J Sex Med. 2010; 7: 2947.
2. World J Urol. 2005; 23: 76
3. Transl Androl Urol. 2016; 5: 549.
Delayed Ejaculation Treatment
Therapies• Behavioral therapy
• Pharmacotherapies → very limited evidence • Testosterone – maybe???• Others…
Overall, few therapies with any evidence of efficacy for the treatment of delayed ejaculation!!
There are no approved therapies
for treatment of DE
Treatment of SSRI-Induced DE• Use when SSRI is likely cause of DE
• Can also switch to different SSRI in same class
• DE treatment with meds up to 70% effective (based on small studies)
Drug PRN Dosage Daily Dosage
Cyproheptadine 4-12 mg (3-4h prior to sex) --
Bethanechol 20 mg (1-2 hours prior to sex) --
Amantadine100-400 mg (for 2 days prior
to sex)75-100 mg BID / TID
Bupropion -- 75 mg BID / TID
Buspirone -- 5-15 mg BID
Loratadine -- 10 mg Daily
Sex Med Rev. 2016; 4: 167.
Andrology. 2015; 3: 626.
Treatment of DE – No SSRIDrug PRN Dosage Daily Dosage
Oxytocin 24 IU intranasal / SL during sex --
Pseudoephedrine 60-120 mg (120-150 min prior to sex) --
Ephedrine 15-60mg (1 hour prior to sex) --
Midodrine 5-40mg Daily (30-120 min prior to sex) --
Apomorphine0.5-1.5mg intranasal (20 min prior to
sex)--
Yohimbine -- 5.4 mg TID
Cabergoline -- 0.25-2 mg BIW
Reboxetine -- 4-8 mg
Imipramine -- 25-75 mg Daily
Sex Med Rev. 2016; 4: 167.
Summary• Orgasmic function is dependent on interplay of numerous
neurohormonal and physical factors
• Norepinephrine, serotonin, dopamine, and prolactin are the primary neurohormones involved
• The causes of PE and DE are not well established
• DE/anorgasmia can be caused by many meds, in particular SSRIs
• Treatment should include psychosexual and medical therapy
• Medical therapies are poorly studied and not FDA approved
Erectile Dysfunction
Erectile Dysfunction (ED)
• Definition: “. . .the consistent or recurrent inability of a man to attain and/or maintain a penile erection sufficient for sexual activity”
Prevalence of ED:Massachusetts Male Aging Study
Feldman HA, et al. J Urol. 1994;151:54-61.
Feldman HA, et al. J Urol. 1994;151:54-61.
Men aged 40 to 70 years (N = 1290)
Shared Risk Factors:ED and Cardiovascular Disease (CVD)
• Hypertension
•Diabetes
•Dyslipidemia
•Depression
• Smoking
• Obesity
• Sedentary Lifestyle
Int J Clin Pract. 1999;53:445-451
Am J Cardiol. 2000;86:1210-1213
Prev Med. 2000;30:328-338.
ED may be the first sign of
underlying CVD!
Erectile
Dysfunction
- Vascular
- Arterial Insufficiency
- Venous Leak
- Endocrine
- Neurologic
- Trauma
Organic
Psychogenic
Iatrogenic
- Prior surgery
-Prostate
-Retroperitoneal
- Medications
Anatomic
-Peyronie’s Disease
-Phimosis
-Marital conflicts
-Guilt
-Performance anxiety
Diagnosis• Laboratory testing
• Testosterone / Free Testosterone
• Hb A1c
• Cholesterol
• Ultrasound (Penile duplex)• PSV < 30 ml/sec (arterial insufficiency)
• EDV > 5 ml/sec (venous leak)
• Physical examination• Penile plaques
• Testicular atrophy
Treatment Options
• Medical (hormonal): Androgens / Testosterone
• Oral therapy: PDE Inhibitors
• ICI therapy: Caverject, Trimix
• Intraurethral Rx: MUSE
• Vacuum Constriction Device
• Penile Prosthesis
5*
Medical Therapy of ED
Sildenafil (Viagra): April 1998
Vardenafil (Levitra): August 2003
Tadalafil (Cialis): November 2003
Udenafil (Zydena): 2005…
Avanafil (Stendra): April 2012
First-Line Treatment for ED:How PDE5 Inhibitors Work
Nitric
OxideGuanylate
Cyclase
PDE5
GMP
GTPcGMP
Smooth Muscle
Relaxation
Erection
*Nonadrenergic, noncholinergic nerve.Boolell. Br J Urol. 1996;78:257-261; Burnett. J Urol. 1997;157:320-324; Heaton. Neurosci Biobehav Rev. 2000;24:561-569.
NANC* Neurons
Endothelial Cells
Summary
• Erectile dysfunction is a common problem
• There is a strong relationship between CVD and ED
• Nearly every man can be successfully treated for ED using a number of therapies: • PDE5 inhibitors / hormone therapy
• Intracavernosal injections
• VED
• Penile prosthesis
Peyronie’sDisease
https://www.aaurology.com/for-patients/our-blog/
Peyronie’s Disease (PD) - Definition
An acquired penile abnormality characterized by fibrosis of the tunica albuginea, which may be accompanied by:
• Pain
• Deformity
• Erectile Dysfunction (ED)
• Penile shortening
• Psychological distress
https://www.auanet.org/education/guidelines/peyronies-disease.cfm
Prevalence of PD
• Prevalence rates have been underestimated
• Overall, 0.5-20.3% of men have PD (≈9%)
https://www.auanet.org/education/guidelines/peyronies-disease.cfm
Dibenedetti DB, et al. Adv Urol.; 2011: 282503.
• Trauma/micro-trauma
• Abnormal wound healing: • Collagen deposition
• Fibrosis
• Calcification
• Peyronie’s (penile) plaque
Photo courtesy of Dr. Hatzichristodolou
HOW DOES PD HAPPEN?
Psychological Impact of PDOften overlooked or underestimated…
• 77% → negative psychological effect
• 48% → clinically significant depression
• 26% → severe depression
• 81% → emotional problems associated with loss of penile length and the ability to have intercourse
• 54% → relationship problems
Nelson CJ, et al. J Sex Med. 2008;5:1985–1990.
Smith JF, et al. J Sex Med. 2008, 5(9): 2179-84.
Nelson C.J, Mulhall JP. J Sex Med 2013, 10(3): 653-60.
Treatment Options for PD
•Oral medications
• Intralesional injection therapy
• Surgery
• Penile traction therapy
• (Shockwave therapy)
Summary• Peyronie’s disease is an abnormal penile curvature / deformity
resulting from fibrous plaque formation in the tunica albuginea
• Peyronie’s disease is more prevalent than previously thought
• PD is highly treatable through a number of options, including injections, traction therapy, and surgery
• There are a number of male sexual dysfunctions
• Male sexual dysfunctions are interrelated and men often present with multiple (i.e. low libido and ED, etc.)
• Male sexual dysfunctions are overall highly treatable
THANK YOU!
@utahurology @apastuszwww.utahmenshealth.com