TD in Men (Male Hypogonadism) an update by Dr Shahjada Selim

1. TESTOSTERONE DEFICIENCY IN MEN
AN UPDATE
Dr Shahjada Selim
Assistant Professor
Department of Endocrinology
Bangabandhu Sheikh Mujib Medical University
Email: selimshahjada@gmail.com
info@shahjadaselim.com

2. Testosterone: Secretion and
Metabolism
• Testosterone is the principal androgen
secreted by the mature testis (interstitial cells
of Leydig)
• Normal young men produce about 7 mg each
day, of which less than 5% is derived from
adrenal secretions

3. Testosterone: Secretion and
Metabolism
• Testosterone in blood is largely bound to
plasma protein, with only about 2 to 3%
present as free hormone
–About half is bound to albumin,
–and slightly less to sex hormone-binding
globulin (SHBG), which is also called
testosterone-estradiol-binding globulin
(TeBG)

4. TESTOSTERONE IN BLOOD
CONCENTRATION

5. Condition associated with alterations
in SHBG concentration

6. With normal testosterone levels
• Muscle growth
• Increased strength
• Bone density
maintenance
• Height stimulation
• Sexual desire
• Energy levels
• Mood
• Nervous system

7. Testosterone Deficiency (TD) in Men
[Male Hypogonadism]

8. CHANGE OF NOMENCLATURE
 Over time name of the condition changes -
Testosterone Deficiency (TD)
 In March 2014, the ISSM Testosterone
Guideline Committee in New York opined a
new generally accepted definition -
Testosterone Deficiency (TD) to replace the
other inconsistent definition like-
― Hypogonadism, (primary, secondary, mixed)
― LOH, androgen deficiency, andropause etc

9.  TD affects 2-6% of adult men, and may
affect the function of multiple organ
systems.
 TD may result in significant detriment in the
quality of life due to alterations in sexual
function, cardiovascular risk, glycemic control,
bone health, and many other aspects of men’s
health.
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10. Factors associated with an
increased prevalence of TD
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11. Causes of TD
 Reduced testicular synthesis of testosterone
due to impaired Leydig cell function (primary
TD)
 Reduced testicular synthesis of testosterone
due to inadequate gonadotropic stimulation
of Leydig cells (secondary TD)
ISSM Quick Reference Guide on Testosterone Deficiency for men4-May-18 TD in Men: Dr Selim 12

12. Klinefelter’s syndrome
Noonan syndrome
Testicular infarction
Hemochromatosis
Some drugs and surgeries
Previous cryptorchidism, mumps orchitis,
testicular trauma, torsion or irradiation.
Medical conditions that may cause
Primary TD include
Cont..
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13. Figure 1
PRIMARY HYPOGONADISM
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14. Medical conditions that
may cause Secondary TD
Cont..
 Isolated hypogonadotropic hypogonadism
 Kallmann’s syndrome
 Prader-Willi syndrome
 Pasqualini’s syndrome
 Primary and secondary CNS tumours
 Diabetes Mellitus
 Obesity
 Hyperprolactinemia
 Sme drugs
 Hypothalamic-pituitary irradiation or surgery.
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15. Figure 2
SECONDARY HYPOGONADISM
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16. Cont..
TD always has a cause; this
should be identified and
documented, and reversible
causes should be effectively
treated.
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17.  Reduced muscle
strength
 Physical frailty
 Impaired concentration
 Impaired verbal memory
 Fatigue
 Tendency to fall asleep
during the day
 Insomnia
 Reduced sense of general well-
being;
 Reduced energy and motivation
 Anxiety
 Depression
 Irritability
 Reduced sexual desire
 Infrequent or absent nocturnal
erections Impaired erectile
 Ejaculatory and orgasmic
function
Common symptoms include:
CLINICAL HISTORY
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18. Clinical sign and symptoms
suggestive of TD
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19. STEP 1:
Total testosterone (TT) assay on serum
from a venous blood sample drawn
between 08:00AM and 12.00PM.
 If TT ≥12nmol/L (346ng/dL); TD is
unlikely
 If TT is <12nmol/L (346ng/dL), proceed
to step 2
LABORATORY DIAGNOSIS
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20. STEP 2:
TT assay on serum from a second venous blood
sample drawn between 08:00AM and 12.00PM
after an interval of at least one week, together
with:
 Serum LH (to distinguish primary and
secondary TD) and prolactin
 In case of obese and older men, sex-
hormone binding globulin (SHBG)
LABORATORY DIAGNOSIS
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21. CALCULATION OF FREE
TESTOSTERONE (WWW.ISSAM.CH)

22. To make a diagnosis of TD, affected
men must have a serum total
testosterone that is consistently <8
nmol/l (231 ng/dl).
And
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23.  Men with a serum total testosterone that is
consistently >8 nmol/l (231 ng/dl) but ≤ 12nmol/L
(346 ng/dL) may have TD and may be offered a
trial of testosterone replacement therapy (TRT);
 a sustained improvement in symptoms over a
period of six months in response to TRT would
confirm the diagnosis.
But
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24.  Treatment of sleep apnea, weight
reduction, and discontinuation of opioid
medication may result in increased testosterone
synthesis.
 Before offering drug treatment, the physician
must identify men who wish to maintain their
fertility and testicular volume, as prescription of
testosterone is highly likely to suppress
spermatogenesis and fertility, and reduce
testicular volume.
Treatment of TD
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25. Treat of TD without Testosterone
 The ISSM Committee recommends that men
who wish to maintain spermatogenesis,
fertility , and the testosterone volume be
referred for specialist management
(e.g.,Endocrinologist, Fertility specialist) until
an approved non testosterone is available.

26.  Clomiphene Citrate blocks estrogen receptors in the
hypothalamus and pituitary and increase GnRH,
LH, FSH release. But no consistent effect on
seminal parameters or pregnancy rates.
 Aromatase Inhibitor (AI) is used for 2ndary
hypogonadism as alternative approach to TRT.
Treat of TD without Testosterone

27.  At the time of publication, preparations of testosterone are the
only pharmacological treatments approved for the indication
of TD, regardless of its cause.
 There are differences between testosterone preparations in
route of delivery, ease of use, pharmacokinetics and cost.
 Choice of treatment should be agreed on with patients
to respect their preferences and promote long-term
compliance.
Treatment of TD
Cont…
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28. Man with TD
Signs and/or symptoms AND repeatedly low TT
Assess possible contraindications or cautions related to TRT Hematocrit,
prostate, others (incl. breast Ca, severe sleep apnoea, severe cardiac failure)
If obese, lifestyle modification and weight loss
exercise, low calorie diet ±medical/surgical intervention
Desire to maintain fertility No desire to maintain fertility
Stimulation of endogenous
T secretion (if LH not elevated) specialist
referral for treatment with ?SERMs ?HCG
± FSH
TRT
Follow-up at 3 and 6 months
Signs and symptoms, weight, TT, Hct, PSA
Not improved after 6 months
Consider discontinuation
Search for other causes/treatments
Improved
Continue 6 month follow up including
annual DRE after age 40 years
Flow chart for the process of care for the assessment and
management of testosterone deficiency in adult men
wishing to maintain fertility
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29. Testosterone Replacement Therapy (TRT)
 Oral testosterone : ISSM TD guideline
committee doesn’t recommend Oral testosterone
preparation with 17 alpha methyl testosterone
preparation.
 Buccal Testosterone: Buccal adhesive tablets
are applied to the gum above the incisor teeth.
Released testosterone over 12 hour period.

30.  Transdermal Testosterone (Skin patches,
gels, axillary spray): 5-10mg Testosterone per
day. Gel preperations are available 1%
sachets.
 Varies within an individual due to change of
skin blood flow.
Testosterone Replacement Therapy
(TRT)

31. Testosterone Long Acting injections:
― Nebido, Bayer, Germany : L/A Testosterone
Undecanoate 1000 in 4mL. After initial injection a further
injection is given after 6 weeks and repeat every 10-12
weeks.
― Aveed, Endo Pharma, Ireland: 750 mg in 3mL. After
the initial injection the 4 weeks later the next injection
and then repeat every 10 weeks. Fewer injection per
year
Contd…Testosterone Replacement Therapy (TRT)

32. Some recommended regimens for
testosterone replacement therapy
BSM 2017

33. Available Products
JAMA April 12, 2016 Vol. 315, Number 14

34. Different Modes Of T Substitution
and Related T-concentration

35. Relative contra-indications of TRT
 ntreated severe sleep apnea,
 a hematocrit >50%,
 severe lower urinary tract symptoms with an
International Prostate Symptom Score above 19,
 uncontrolled or poorly controlled heart failure,
 a MI or cerebrovascular accident within the past
6 months,
 a personal or family history of a procoagulant
state, or a personal history of thromboembolism
Testosterone and Cardiovascular Risk, Endocr Prac. 2015;21(No. 9)

37.  The effect of Testosterone Replacement Therapy
(TRT) on symptoms reduction are assesssed and
enquiry about side effects be made 3, 6 and 12
months after initiating TRT and annually there after.
 Testes to be covered
―TT (target range is mid point of the reference
range for a young adult)
―Lipid profile
―Hematocrit
―PSA (men above 40 years)
Testosterone Replacement Therapy
(TRT) Follow-up

38. TRT follow-up
 Patient should be monitored every 3-6
months during first year and at least
annually thereafter.
 Each visit careful clinical & andrological
evaluation

39. TRT follow-up
 Digital Rectal Examination is mandatory (as per
the ESSM guideline)
 PSA, hematocrit mandatory
 Consider prostate biopsy if PSA is more than
4ng/ml, or PSA concentration>1.4ng/ml within
any 12 mo period of TRT

40. TRT outcomes
 Compared to placebo TRT significantly
improved all aspects of sexual function in the
studies of middle ages and elderly men with
low T (T concentration <12nmol/l, 346ng/dl
 No EFFECTS observed on TRT if the
baseline Testosteron levels higher than 12
nmol/l

41. TRT outcomes
 More severe hypogonadism more significant or
impressive are the result of improvement.
 TD is the main cause of ED in younger men while
it is one of the multifactorial ED in older ones (like
DM, dyslipidaemia, metabolic syndrome, Sp Cord
Injury etc)

42. TRT outcomes
 Combination of TRT and PDE5I (sildenafil,
tadalafil ) can be used to improve the outcomes
of PDE5I in hypogonadism.
 TRT is associated with reduction in bone
resorption and increase lumber bone mineral
density.

43. Conclusion: managing TD
 Sexual function such as libido, erection and
ejaculation are clearly testosterone dependent
with different T-cut off values regarding onset of
clinical symptoms
 To get maximum effect of TD patients both TRT
and PDE5I (sildenafil, tadalafil) should be given to
get the maximum PDE5I response.

44. TAKE HOME MESSAGE
 No EFFECTS observed on TRT if the baseline
Testosterone levels higher than 12 nmol/l
 Testosterone Deficiency (TD) causes ED and low
libido and after testosterone replacement therapy
both function improves.
 Maximum effect reached after 2-3 months of
treatment with TRT.
 Oral testosterone (17 alpha methyl testosterone is
not recommended by ISSM committee on TD due to
hepatotoxic side effects and hepatoma.

45. www.shahjadaselim.com
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