Download LeRoy A. Jones, MD President Society Urologic Prosthetic Surgeons

Survey
yes no Was this document useful for you?
   Thank you for your participation!

* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project

Document related concepts

Epidemiology of metabolic syndrome wikipedia , lookup

Hyperandrogenism wikipedia , lookup

Transcript
Hormone replacement
therapy in Men
LeRoy A. Jones, M.D.
President Society Urologic
Prosthetic Surgeons
Urology San Antonio
Clinical, Associate
Professor Urology
University of Texas HSC
San Antonio
San Antonio, Texas
2
Testosterone Replacement
Progressive decline in serum testosterone with
aging
Pharmaceutical industry involvement
Multibillion dollar industry!
3+ million men on US on T replacement!
Fountain of Youth?
Testosterone Regulation:
Hypothalamic-Pituitary-Gonadal (HPG) Axis
Hypothalamus
Pituitary
gland
1. Gonadotropin-releasing hormone (GnRH)
secreted from the hypothalamus stimulates
anterior pituitary
2. Anterior pituitary releases follicle
stimulating hormone (FSH) and
Hypothalamus
luteinizing hormone (LH)
FSH
Anterior
pituitary
Testes
LH
Posterior
pituitary
Spermatozoa
(-)
Testosterone
(-)
FT-01423/June 2011
Dandona4P, Rosenberg MT. Int J Clin Pract. 2010;64(6):682-696.
3. LH stimulates
Leydig cells
in the testes
to produce
testosterone
4. FSH stimulates
Sertoli cells in
the testes to
produce
spermatozoa
The Distinction Between Bioavailable
and
Total Testosterone: Why It Matters
Bioavailable testosterone
SHBG-bound
Albumin-bound
Free
60%
38%
2%
Total testosterone
5
SHBG, sex hormone–binding globulin.
Braunstein GD. In: Basic & Clinical Endocrinology. 5th ed. Stamford, CT: Appleton & Lange; 1997:422-452.
Testosterone Deficiency
Testosterone deficiency (TD) is a clinical
and biochemical syndrome characterized by
a deficiency of testosterone, or testosterone
action, and relevant symptoms and signs.
ISSM 2014
Symptomatic Hypogonadism
T< 15nmol/L
loss libido/ energy
T< 12nmol/L (346ng/dL)
obesity
T< 10nmol/L
depression, sleep disturbance, poor
concentration
In the Hypogonadism in Males (HIM) Study,
the Prevalence of Hypogonadism Was
Estimated to Be Nearly 40%
• The HIM study estimated the prevalence of hypogonadism (< 300 ng/dL) in 2165 men
over 45 presenting to 95 primary care practices in the United States
Prevalence of Hypogonadism, %
60.0
50%
50.0
40.0
46%
39%
40%
40%
55–64
65–74
34%
30.0
20.0
10.0
0.0
Total
45–54
(45+)
8
Mulligan T et al. Int J Clin Pract. 2006;60(7):762-769.
75–84
85+
Age Range, years
FT-01423/June 2011
Reprinted from Int J Clin Pract, 60, Mulligan T, Prevalence of hypogonadism in males aged at
least 45 years: the HIM study, 762-769, 2006, with permission of John Wiley & Sons, Inc.
Common Comorbidities Among
Hypogonadal Men in the HIM study
•
A history of hypertension, hyperlipidemia, diabetes, and obesity were each
reported significantly more often by hypogonadal men compared with eugonadal
men in the HIM study
p<0.001
Patients, %
p<0.001
9
Mulligan T et al. Int J Clin Pract. 2006;60(7):762-769.
p<0.001
FT-01423/June 2011
p<0.001
Endocrine Society Guidelines for
Screening for Low T
Screening for low T is not recommended in all patients
Recommended Patients to Screen
NOT Recommended to Screen
• Type 2 diabetes mellitus
• General population
• Treatment with medications, including
opioids and glucocorticoids
• HIV-associated weight loss
• End-stage renal disease and
maintenance hemodialysis
• Moderate to severe chronic obstructive
lung disease
• Infertility
• Osteoporosis or low trauma fracture
• Sellar mass
10
Bhasin S et al. J Clin Endocrinol Metab. 2010;95:2536-2559.
FT-01423/June 2011
Low T Screening Tools
While the general population should not be screened, the
following tools can aid in diagnosis for patients where screening is
recommended
Endocrine Society guidelines recommend testing total
testosterone by2
 Morning blood draw
 No role for free testosterone (assay variability)
 LH, PRL with repeat Testosterone
 SHBG in obese and elderly
2. Bhasin S et al. J Clin Endocrinol Metab. 2010;95:2536-2559.
11
9. Gavrilova N, Lindau ST. J Gerontol B Psychol Sci Soc Sci. 2009;64 (suppl 1):i94-i105.
FT-01423/June 2011
The Endocrine Society Clinical Practice
Guideline (2010) for Evaluation of Adult Men
With Suspected Hypogonadism
History and physical (signs and symptoms)
Morning total T
Normal T
Low T value
Exclude reversible illness, drugs, nutritional deficiency
Repeat T [use FT or BT if suspect altered SHBG]
LH + FSH
SFA [if fertility issue]
Follow-up
Confirmed low T (eg, total T 280–300 ng/dL)
or FT or BT < normal (eg, FT 5–9 ng/dL)
Low T, low or normal LH + FSH
(Secondary)
Low T, high LH + FSH
(Primary)
Normal T, LH + FSH
BT, bioavailable testosterone; FSH, follicle-stimulating hormone; FT, free testosterone; LH, luteinizing hormone;
SFA, seminal fluid analysis; SHBG, sex hormone-binding globulin; T, testosterone.
12al. J Clin Endocrinol Metab. 2010;95:2536-2559. FT-01423/June 2011
Bhasin S et
Bhasin S, Journal of Clinical Endocrinology & Metabolism, Testosterone therapy in men with androgen deficiency
syndromes: an Endocrine Society clinical practice guideline, 95, 6, 2010, 2536-2559. Copyright 2010, The Endocrine Society.
Testosterone Deficiency Treatment
TRT Modality
Topicals
• Gel
• Patch
• Solution
Injection
Buccal system
Subcutaneous pellets
Current TRT modalities
Application site and dose are not interchangeable across products
FT-01423/June 2011
1. Dandona P et al. Int J Clin Pract. 2010;64(6):682-696. 3. FORTESTA™13
Gel [Prescribing Information]. Chadds Ford, PA: Endo
Pharmaceuticals Inc; 2011. 14. Axiron® [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2011.
Testoterone preparations
Nieschleg E. Best Pract and Research Clinical Endo/Meta 29 (2015) 77-90
Testopel
Testosterone Therapy Delivery
Systems: Adverse Effects
Oral tablets
Effects on liver and cholesterol (methyltestosterone)
Pellet implants
Require surgical procedure
Infection, expulsion of pellet
Intramuscular injections
Fluctuation in mood or libido
Polycythemia (especially in older patients)
Transdermal patches
Skin reactions at application site
Transdermal gel
Potential risk for testosterone transference to partner
Tenover JL. Endocrinol Metab Clin North Am. 1998;27:969-987.
Arver S, et al. J Urol. 1996;155:1604-1608.
Parker S, et al. Clin Endocrinol (Oxf). 1999;50:57-62.
Follow-up
3-6 months for the first 1-2 years, yearly
thereafter
Laboratory evaluation: PSA, lipids,
Hematocrit, testosterone
Testosterone Replacement
Positive effects:
Obesity
Metabolic Syndrome
Diabetes
Osteoporosis
Hypogonadism and Infertility
Exogenous testosterone will suppress
spermatogenesis
AUA survey- 25% of urologist will treat
infertile man with testosterone!
Recovery of spermatogenesis 5-9 months
Hypogonadism and Infertility
HCG combination therapy for recovery of
spermatogensis due to T use
49 men azoospermia/ severe oligospermia
Combination HCG (3000 units SQ qod)
supplement with clomophene citrate,
anastrozole or recombinant FSH
47 (95.9%) recovered by 4.6 months, density
22.6 million/mL
J Sex Med 2015 Jun;12(6) 1334-7
Hypogonadism and Infertility
Selective Estrogen Receptor Modulators:
Clomiphene citrate- off label use
2 dia-stereoisomers: zuclomiphene and
enclomiphene (half-life)
Enclomiphene Citratecorrection of serum testosterone
promote spermatogenesis
Prostate Cancer
Prostate cancer stimulated by testosterone
based on one patient (Huggins/Hodges
1941)!
No evidence the T replacement causes
prostate cancer
Saturation Model (120ng/dl)
Pts with Pca being treated
Conclusion
Testosterone replacement therapy is safe
Evidence based guidelines for follow up is
important
Determine reproductive status of the patient
Treatment in the Pca pt should be by specialist
in this area
Need large randomized controlled trials
Obrigado
supsweb.org