male gonadal function and dysfunction (male hypogonadism)
DESCRIPTION
Male gonadal function and dysfunction (male hypogonadism). Emphasis where made on the causes, types of male hypogonadism, diagnosis and treatment methods.TRANSCRIPT
MALE GONADAL FUNCTIONS AND DYSFUNCTIONS
SAHEED OLUWASINA OSENI (DVM)
REPRODUCTIVE ENDOCRINOLOGY
(BSC 6936)
FLORIDA ATLANTIC UNIVERSITYDEPARTMENT OF BIOLOGICAL
SCIENCES
BY:
SAHEED OLUWASINA OSENI (DVM)
CLASS PRESENTATION
PRESENTATION OUTLINE
Quick Overview Male gonadal (Testicular) functions Male gonadal Dysfunction (Androgen
Deficiencies) Male Hypogonadism Secondary hypogonadism-Opiates , Kallman’s
syndrome and idiopathic hypogonadotropic hypogonadism
Primary hypogonadism-Klinefelter’s syndrome, Nooman’s syndrome and XX males
Questions and Answers References
Hypothalamic-Pituitary-Testicular Axis
1. Tubular compartment
Germ cells
Sertoli cell: also known as the nurse or mother cells or sustentacular cells support spermatogenesis. Their proliferation is triggered by testosterone and FSH secretion (has FSH-receptor on its membranes) and also Inhibited by inhibin.
Sperm cells
Two cellular compartments involved in spermatogenesis
2. Interstitial Compartment
Leydig cells:Produce testosterone (dihydrotestosterone, DHEA and androstenedione) by respond to luteinizing hormone (LH) with steroid production (primarily testosterone).
Functions of testosterone
Converted to DHT (more active)in tissues e.g. prostate gland.
Testosterone is also converted to oestradiol in adipose tissue by aromatase enzyme
Actions– Male sexual differentiation– Maintains male secondary sexual characteristics – Regulation of GnRH secretion– Spermatogenesis– Normal male sexual function and behaviour– Maintenance of bone mineral density
TESTOSTERONE TARGET ORGANS AND FUNCTION
DHT &Estradiol
***This will be a hard task for someone with hypogonadism due to fatigue and loss of strength***
I’VE GOT THE ‘T’ FOLKS
Androgen Deficiency Symptoms
Musculoskeletal – Decreased vigour and physical energy– Diminished muscle strength
Sexuality– Decreased interest in sex– Reduction in frequency of sexual activity– Poor erectile function/arousal– Loss of nocturnal erections– Reduced quality of orgasm– Reduced volume of ejaculate
Mood disorder and cognitive function– Irritability & lethargy– Decreased sense of well-being– Lack of motivation– Low mental energy– Difficulty with short-term memory– Depression– Low self-esteem– Insomnia– Nervousness
Androgen Deficiency Symptoms
Vasomotor and nervous– Hot flushes– Sweating
Androgen Deficiency Symptoms cont’d
– Diminished muscle mass
– Loss of body hair
– Abdominal obesity
– Gynecomastia
– Testes frequently normal, occasionally
small
Physical Signs
Androgen Deficiency Symptoms
History and Physical (Symptoms and Signs)
Exclude reversible illness, drugs,
nutritional deficiency
Do you suspect altered SHBG?
Low T
Morning Total T
Normal T, LH+FSH
Not HypogonadismFollow up
Normal T
Repeat TCheck LH+FSH
If altered SHBG,
Use free or bio- T
Semen analysis
if fertility issue
Keys: ‘T’ means Testosterone
How to investigate for Androgen Deficiencies
MALE HYPOGONADISM: Definition
A decrease in either of the two major functions of the testes: – sperm production – testosterone production
Types of Male Hypogonadism
Secondary hypogonadism
Primary hypogonadism
Confirmed low T (Total < 300 ng/dl)OR
Free or Bio T < normal (Free T <5 ng/dl)
Low TLow / normal LH+FSH
Prolactin, iron saltsOther pituitary hormones
Low THigh LH+FSH
KaryotypeKlinefelter SyndromeOther Testicular Insult
Secondary HypogonadismPrimary Hypogonadism
MRI in certain cases
How too know which type of hypogonadism you are dealing with
during tentative diagnosis
Secondary hypogonadism
Hypothalamic/pituitary cause (often presents as delayed puberty or infertility)
Genetic, structural or environmental causes
Possible aetiologies
Kallman’s syndrome
Failure of GnRH secretion and neuronal development Associated with anosmia (smelling disorder) and
hyposmia (75%) 1 in 10,000 Male : female ratio 4:1 Diagnosis
– Low/undetectable testosterone, LH and FSH– Other pituitary functions are normal– Normal hypothalamus/pituitary on MRI, but absence of
olfactory bulb Treatment
– Exogenous testosterone replacement– Gonadotrophins if fertility required
Idiopathic hypogonadotrophic
hypogonadism Acquired or genetic (rare cases of GnRH
receptor gene mutation) In acquired cases men may
– have gone through normal puberty– Present with low libido, erectile dysfunction
or infertility– Acquired cases may go into remission
after testosterone or gonadotropin therapy.
Miscellaneous causes of secondary hypogonadism
Stress Systemic illness Structural
– Any pituitary tumour esp. prolactinomas– Associated with other hormonal deficiencies
Drugs– Anabolic steroids– Cocaine and opiates– Any drugs causing hyperprolactinaemia
Hemochromatosis Endocrine – Cushing's, prolactinoma Prader-Willi syndrome – 15q mutation – obesity and
mental retardation Laurence-Monn-Biedl syndrome – obesity and mental
retardation.
Primary hypogonadism
Genetic– Klinefelter’s syndrome– XX males– Noonan’s syndrome (46XY)
Acquired– Trauma– Orchitis– Cryptorchism– Post chemotherapy/radiotherapy– Chronic illness– Drugs- opiates, alcohol, sulfasalazine, colchicine
Opiates and hypogonadism
Long-acting opioid analgesics suppress the hypothalamic-pituitary gonadal axis in men and produce symptomatic androgen deficiency (up to 74%).
Opiates of all kinds cause reduced release of GnRH, LH, testosterone (free testosterone).
This usual follows a dose dependent exposure and
correlates to reduction in libido and subjective erectile dysfunction.
Also leads to osteoporosis
NB: **I did not find any literature on special treatment or testosterone replacement in this group. (though I suspect using a opioid antagonist or stopping use of opiates might work)
Hypogonadism in men consuming sustained-action oral opioids. Daniell HW. J Pain. 2002 Oct;3(5):377-84.
Klinefelter’s syndrome
First described by Harry Klinefelter 1942 1:500 men affected Extra X chromosome causes primary hypogonadism
with testosterone deficiency Clinically
– Reduced testicular volume– Tall eunachoid stature– Reduced body hair– Gynaecomastia– Intellectual dysfunction in 40%
20 time increased risk of carcinoma of breast
Klinefelter’s Syndrome
Most common endocrine cause of Primary hypogonadism
FSH always T variably affected (T or normal) Fertility rare (in mosaics only) Treatment: T only if needed
– Will not reverse infertility
Signs: Eunuchoidal body
habitus Variable
androgenization Long extremities
(LS>US) Karyotype: XXY
Klinefelter’s Syndrome
NB: So the klinefactor is having 47 chromosomes instead of 46
Trisomy
Diagnosis
Low testosterone Elevated LH/FSH Azospermia Definitive diagnosis is
based on karyotyping– 47XXY or 46XY/47XXY
(mosaic)
Management
Counselling– Klinefelter’s Syndrome
Association UK[http://www.ksa-
uk.co.uk]
Androgen replacement therapy
Noonan Syndrome
Autosomal dominant disorder (variable penetrance) Normal karyotype Phenotype is like that of Turners syndrome
– Low set ears– Right sided congenital heart defects (left-sided in
Turners)– Epicanthic folds– Short stature– Webbed neck– Cryptorchism (50% of males)– Primary hypogonadism
Can affect either sex
XX males
1 in 10,000 births These patients have a translocation of
part of the Y chromosome with the X chromosome
Phenotype is similar to Klinefelter's May also have short stature and
hypospadias
QUESTIONS &
ANSWERS
CASE STUDY TO DISCUSS IN CLASS
A 35 year old man presents with infertility & azoospermia. He was at puberty at the age of 15, has normal libido and shaves every other day.
He is 72” tall, 180#, with gynecomastia and small testes Has normal thyroid & phallus The Testosterone level is low, LH high, FSH high
QUESTION??? Can you guys give me your tentative diagnosis with
reasons and also the best diagnostic test to establish your definitive diagnosis?
o
Friends its time for us
to think as a clinician and endocrinolog
istk
oCase 1
CASE STUDY TO DISCUSS IN CLASS
A 19 year old boy presents with inability to smell his girl friends perfume & azoospermia
He is 175cm tall, 53kg weight, with his arm slightly than his height at 177.5cm. He had a normal voice and his pubic hair were adult like in texture and type.
On endoscopy his olfactory fissures were patent and MRI images shows that the olfactory bulb is absent.
The Testosterone level is low and other pituitary functions were found to be normal with MRI.
QUESTION??? Can you guys give me your tentative diagnosis with
reasons and what type of hypogonadism is this disease?
o
Friends its time for us
to think as a clinician and endocrinolog
istk
oCase 2
CASE STUDY TO DISCUSS IN CLASS
A 54 year old man was asked by his wife of 35years old to go visit a physician concerning his inability to perform well in bed (low libido and erectile dysfunction). The man in addition complaint to the clinician about a long time worsening fatigue.
On physical examination, he is found to be obese with BMI=31. There is no evidence of gynecomastia The testicles and prostate are normal Lab evaluation reveals serum testosterone level of 180ng/dl (ref. range: 249-836)
QUESTION??? What is your tentative diagnosis and why?
o
Friends its time for us to
think as a clinician and endocrinologi
stk
oCase 3
THANKS FOR LISTENING
Total vs. Free vs. BioavailableTestosterone (male)
60%
38%
2%
Affinity for SHBGis at least 4X higher vs. albumin
Greenspan’s Basic &Clinical Endocrinology, 8th edition
REFERENCES
Greenspan’s Basic &Clinical Endocrinology, 8th edition
Per Williams Textbook of Endocrinology 11th edition
[http://www.ksa-uk.co.uk] Wikipedia [www.wikipedia.org]: kallman’s,
klinefecter’s, Nooman’s syndrome, XX males, etc....