Testosterone

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1. Blood flow interference. 2. Loss of elasticity. 3. Sensory afferent signals diminished. 4. Interpretation of signals less sexual. Testosterone may be playing a ... (frequency of REM sleep erections is tightly related to T deficiency) and is reversed with. TRT. • Visual erectile response more androgen independent systems but ...

Testosterone and Sexual Function Seacourses July 22 – August 3 2017

Stacy Elliott, MD Clinical Professor, Depts. Psychiatry and Urologic Sciences University of British Columbia, Vancouver BC Medical Director, BC Center for Sexual Medicine, UBC Sexual Medicine Consultant, MHI and PCSC, VGH PI, ICORD, Blusson Spinal Cord Building

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Objectives • Understand the role of testosterone in male sexual functioning • Appreciate the consequences of abnormally low testosterone on erection, ejaculation and orgasm • Describe the known role of testosterone in women • Discuss the differences in men and women’s replacement of testosterone

This talk based on current literature... • Canadian Guidelines ( Canadian Men’s Health Foundation) :CMAJ Dec 2015 • Consensus conference of International experts (King’s College London and International Society for the Study of the Aging Male) Fundamental Concepts: Mayo Clinic Proceedings: July 2016 • Expert Colloquium ( Sexual Medicine Society of North America) AOH: Mayo Clinical Proceedings: July 2016

Testosterone Biosynthesis

Male Reproductive

Hypothalamus

Hormonal Axis

GnRH Pituitary

(-)

(-) Estradiol

LH Leydig cells

FSH

Testicles

Sertoli Cells

Aromatase

Testosterone 5∞reductase

DHT

Spermatogenesis

Testosterone: Target Organs Post puberty: Homeostasis & Metabolic Agent

brain libido, mood, cognition

skin hair growth, balding, sebum production

muscle strength, volume, energy reduction in visceral fat

heart cardiovascular health

liver protein synthesis

kidney male sexual organs penile growth spermatogenesis, erection prostate growth and function

bone marrow stimulation of stem cells

stimulation of erythropoietin production

bone strength and density

Signs and Symptoms of TDS Order of Appearance

Mild

Severe

• • • • • • • • • • • • • • •

Decreased libido Decreased vitality Fatigue Mood changes Insomnia Anemia Delayed ejaculation Flushes Erectile dysfunction Decreased muscle mass Increased visceral body fat Testicular atrophy Weakness Osteopenia/osteoporosis Loss of facial, axillary and pubic hair

Signs and symptoms* associated with testosterone deficiency syndrome • Sexual: Decreased libido; erectile dysfunction; decreased frequency of morning erections; delayed ejaculation , reduced seminal volume, anorgasmia • Somatic: Increased visceral body fat/obesity; decreased lean muscle mass; decreased strength; fatigue/loss of energy; decreased physical activity/ vitality; low bone mineral density; anemia; flushes; loss of facial, axillary and pubic hair/slow beard growth; decline in general feeling of well-being • Psychological: Depression/depressed mood; mood changes; irritability; inability to concentrate; insomnia/sleep disorders * May be subtle

Diagnosis of Hypogonadism (HG) • Classical primary HG: testicular failure ( Low T, elevated LH,FSH : hypergonadotrophic HG) • Secondary HG: central (low T, low LH,FSH secondary to GNRH or LHRH failure : hypogonadotrophic HG) • Adult onset hypogonadism (AOH) is a subgroup of men with signs and symptoms of HG without an adequate pituitary response to low T levels (normal or low levels of LH FSH, i.e. functional hyposecretion at the level of both the pituitary and the testes)

What happens to sexual function when testosterone levels decline?* 1st : 2nd: 3rd: 4th:

sexual drive /libido changes ejaculatory changes loss of nocturnal erections loss of daytime/erotic erections

Depression will have low libido, generalized ED but not delayed ejaculation ( unless age related) * Younger verses older man

Aging and lowered T - Age is not a specific risk factor for HG - Age alone is associated with little decline in mean total T levels ( > 40 years) until 70s and 80s - SHBG does increase with age, so bioavailable T (BioT) falls faster than total T (TT) - The lowering of T is more correlated with comorbidites, (DM, hypertension, hyperlipidemia, asthma/COPD and/or kidney disease) regardless of age - ≥ BMI of 30 kg/m² tripled the risk of symptomatic HG (normal weight men 1:6, BMI > 35 kg/m² 2:3) - Low T likely a marker of poor health

Who needs it ? Watch for symptoms in high risk groups • • • • • • • • • • •

Metabolic syndrome and diabetes Obesity Untreated sleep apnea Head trauma or radiation Chronic neurological diseases ( SCI, MS,etc) Other chronic disease processes ( CRF, COPD) Refractory depression Anemia and sarcopenia of undetermined origin HIV and weight loss Glucocorticoid or opioid therapy ED with failed trial of PDE5i

May be elevated

Orgasmic threshold

Ejaculation Orgasm

May be altered ↓Semen volume

lIncreased duration plateau phase

Arousal (Erection)

Refractory period Increased duration

Sexual Function Changes with Age spontaneous & a.m. erections  rigidity of erection: faster detumescence  pre-ejaculatory sensation  force/volume of ejaculation  need to ejaculate Less orgasmically driven: more intimacy driven

Sexual Manifestations of TD Different phases of sexual response are affected differently Looking at - Sexual desire ( libido) - Genital arousal ( erection) : REM, self, partner - Subjective arousal ( brain – likley estrogen) - Ejaculation fluid volume - Orgasmic threshold - Orgasmic quality and penile and erogenous zone sensitivity - Psychologically :men with SD and lower T show + correlation with depressive and anxiety symptoms (higher T showed better sex functioning, penile blood flow, better relationships but more histrionic traits)* Bandini et al 2009

Three main sexual symptoms correlated with low T • Decreased nocturnal erections • Decreased frequency of sexual thoughts • Erectile dysfunction • These were at TT < 11 nmol/L and free T levels < 220 ( Wu et al 2010)

Sexual Interest/Libido Complex interaction of biological urge ( driven by testosterone, mood and chemical brain factors) and motivational factors ( what the sexual payoff is perceived to be)

What can lower drive as one ages? Poorer health Depression Lowered testosterone Other endocrine abnormalities Poor sexual payoff:pain, lack of sensation, etc Disinterested or loss of partner Sex doesn’t have the same priority

Prevalence of decreased libido with age • Men aged more than 50 years report a threefold increase of the prevalence of decreased libido • Predictors are health and lifestyle factors - alcohol use - poor health - stress - previous adverse sexual experiences Laummann JAMA 1999;281:537-544

Testosterone and Libido • A decrease of libido (sexual desire) has been reported with aging in men1,2 • Adequate plasma testosterone levels are required (but not sufficient) for maintenance of normal libido3 • Testosterone deficiency dose-dependently decreases libido. However, the threshold level of testosterone under which libido problems occur is relatively low3

• Reduced libido in aging men is associated with deficiency of bioavailable testosterone2,4, but not of total testosterone4 1Laumann

et al. JAMA 1999; 281(6):537-43. et al. J Clin Endocrinol Metab 1983;57(1):71-7. 3Buena et al. Fertil Steril 1993; 59(5):1118-23. 4Schiavi et al. Psychosom Med 1991;53(4):363-74.

2Davidson

Is there at minimum level for T and libido? • There appears to be a minimum level of testosterone therapy necessary for adequate sexual functioning, above and beyond which additional levels have no effects • This may vary per individual, and per age ( (i.e castrate levels of T in potent young castratas vs Prostate Ca older patients ) and with other strong biopsychosocial factors • In LOH patients , it has been demonstrated that when T levels fall 12 nmol/L) • All T levels normalized within 6 – 8 weeks • 12/22 has significant improvement in sexual desire domain (4.5 to 8.4) and erectile function ( 12 to 25), most taking 12 – 24 weeks to see max effect • Remaining 10/22 had improved sexual desire but not erection function Yassin and Saad J Sexual Med 2007;4:497-501

Summary: T and Libido • Hallmark symptom of hypogonadism • Libido multifactorial (but T = organic ) • Poor correlation of what level correlates with poor libido ( individualized) • However, many levels of evidence lower T affects libido and frequency of sexual thoughts • Wu et al 2010 : threshold TT
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