Got Low T?

We Got Answers
Angela Bobak, Alex Barbera, Kiana Murdock, Jess Neill, Reagan
Rush, Ryan Kirdahy, Zach Herman
Background, Interaction with Hormones
The Basics
Steroid hormone
Cholesterol derivative
4 member ring system http://opexfit.com/boost-testosterone-naturally/

Androgen
Patterns of testosterone release
Primary male sex hormone
Reproductive and nonreproductive organs

https://www.slideshare.net/arijabuhaniyeh/reproductive-system-48480354
Where Does Production Begin?
Gonadotropin Releasing Hormone (GnRH) is released from the Hypothalamus to

the anterior pituitary.

Binds to receptors in the pituitary gland that in turn release Luteinizing Hormone

(LH) and Follicle Stimulating Hormone (FSH).

Travels via the bloodstream to the testes

What is the role of Luteinizing Hormone?
Stimulates the production of testosterone in the testes
Binds to LH receptors that are located on Leydig Cells
Adjacent to seminiferous tubules
A series of reactions that take place within the Leydig Cells converts
pregnenolone to testosterone.
Testosterone is released into the bloodstream to interact with target tissues:
Liver
Muscles
Must be converted to Dihydrotestosterone (DHT) by 5-alpha-reducatse
Prostate and reproductive system
What is the Role of Follicle Stimulating Hormone?
Plays an important role in spermiogenesis

Initiates the production of Androgen Binding Protein by Sertoli Cells

Concentrates testosterone

FSH binds to nurse cells in the seminiferous tubules and aid with sperm

production and maturation

Inhibin: negative feedback in hypothalamic-pituitary-gonadal axis

Adrenal Glands and Testosterone
Production of dehydroepiandrosterone in the zona reticularis

DHEA

DHEA-S

Primary source of testosterone in women

Production in the ovaries is converted straight to estrogen

Suffer from virilization when testosterone is overproduced

Age Effect On Testosterone Level
 Age Effect On Testosterone Level
This chart breaks down the normal ranges of testosterone by age according to the
Mayo Clinic

Age: Testosterone Level(ng/dL):

0- 5 months 75-400
6 mos.-9years <7-20
10-11yrs. <7-130
12-13 yrs. <7-800
14 yrs. <7-1,200
15-16 yrs. 100-1,200
17-18 yrs. 300-1,200
19+ yrs. 240-950
Ave. Adult Male 270-1,070
30+ yrs -1% per year
Fetal Development
Fetal Development
Wolffian Ducts becomes:
Rete Testis
Efferent duct
Epididymis
Seminal vesicles
 The period during which the secondary sex characteristics
Puberty begin to develop and the capability of sexual reproduction is
attained.- biology.org
Puberty
Puberty
Characteristic changes during puberty:

Facial hair development

Increased muscular body frame
Deeper voice
Increased sexual interest
Increase facial masculinity
Increased sebaceous gland
production
Late Adulthood
Late Adulthood
Symptoms of androgen deficiency of the aging male:

Loss of libido
Erectile dysfunction
Depression
Decreased cognitive ability
Lethargy
Osteoporosis
Loss of muscle mass and strength
Late Adulthood
Reasons for Testosterone Decrease in Older Males :

Diminishment of testicular production of testosterone

Reduced hypothalamic secretion of gonadotropin-releasing
hormone resulting in minimized luteinizing hormone secretion
Poor nutrition
Illness
Medication
Inactivity
Excessive alcohol consumption
Natural aging process
 Kahoot
https://play.kahoot.it/#/k/4acb4e09-d735-4145-ac60-d44d82ec963b
Effect on Body Systems
Central Nervous System
-testosterone acts via androgen receptors in androgen-responsive tissues: brain,
prostate, testes, ovaries, and adrenal glands

-testosterone transported:

Sex hormone binding globulins: 60-70%

Loosely bound to albumins: 30-40%

Free-form: 0.5-2%

Cross the blood brain barrier and influence neuronal cells

Locations of Androgen Receptors in Male Rat Brain Tissue

http://cheap-auto-insurance-in-florida.com/dedicated-study-human-anatomy-brain/human-anatomy-brain-diagram-picture-of-brains-and-function-ventri
(Norris, David, & Carr, 2013) cles-septum-basal-ganglia-thalamus-fornix-amygdala-pituitary/
Neuroprotective and Neurotrophic Actions
Neuroprotection: an effect that may result in salvage, recovery, or regeneration of the
nervous system, its cells, structure, and function

-T protect spinal cord neurons against glutamate, cognitive diseases

-Downfalls: estrogen vs. testosterone/ methamphetamine-induced toxicity

Neurotrophic Actions: neuronal differentiation and increase in neurite outgrowth

-T linked to increase in neuron somal size, neuritic growth, plasticity, and

synaptogenesis in several populations of motor and autonomous neurons
Testosterones Role in Age-Related Diseases
Neurodegenerative diseases characterized progressive dysfunction and death of
neurons

Lowered T induce atrophy and impair compensatory responses in insulted tissue:

aging brain susceptible to degeneration

Glial fibrillary acidic protein (GFAP) marker of astrocyte degeneration and

neurodegeneration

Higher GFAP levels in aging than young rats

T therapy reversed this trend

Preventative role in Mild Cognitive Impairment
MCI: cognitive decline associated with negligible functional loss

Significant neuronal loss in hippocampus and lowered blood flow in subiculum

T therapy in aging mice decreased age-related impairment of learning and

memory

T administration to healthy men 60-75 years of age for 3 months

T levels increased to level in young men = enhanced spatial cognition

Preventative Role in Alzheimers Disease
AD: deposition of senile plaques in affected brain: senile plaque formed amyloid-B
peptide (derived metabolism amyloid precursor protein)

Prevention of heat-shock Tau protein hyperphosphorylation

Normal Tau proteins stabilize cytoskeleton

Tau protein neurological hallmark of AD

Changes in APP metabolism

High doses of T increase levels of precursor APP with decreased metabolites of

amyloid-B peptides
Nerve Regeneration with Facial Nerve: Hamster
Testosterone
Administration

Tibialis Sciatic Nerve: Rabbit Hypoglossal Nerve: Rat

Testosterones Role in Motor Neurons

Motor neuron diseases characterized by progressive

weakness affecting skeletal muscle groups

Androgens alter morphology, survival, and

axonal regeneration
https://www.ausmed.com/articles/nursing-care-of-patients-with-motor-neuron-disease/

Motor neuron hybrid cells in presence of androgens develop larger cell bodies and
broader neuritic processes

Direct neurotropic effect of androgens on lower motor neurons, mediated through AR

 Testosterones Role in
Muscle Development
Both T and DHT bind and activate AR to regulate gene
expression

AR gene expressed widely in myoblasts, myofibers, and

satellite cells of males and females

Androgens may modulate circulating levels of IGF-1: potent anabolic agent in muscle

Serum levels of IGF-1 WT and ARKO males did not differ

Likely that anabolic actions of androgens in skeletal muscle not mediated via
IGF-1 production or action
Study conducted on male AR knockout (ARKO) mice
In males, androgens act through the AR to regulate multiple gene pathways that
control muscle mass, strength, and fatigue resistance

ARKO Mice Physiology What Results Imply About T

Function
Decreased muscle mass Achieve peak muscle mass

Decreased Fast Twitch Muscle Increases Force Production/Strength

Increased Slow-Twitch Muscle Decreased Fatigue Resistance

Same Value of Serum IGF-1 Levels Anabolic Actions Skeletal Muscles Not
Mediated IGF-1
Testosterones Role in Bone Development
Most cases of osteoporosis (men) are due to low testosterone

Is increased bone density due to increased testosterone or due to conversion of

testosterone to estrogen?

Supplement with testosterone instead of estrogen due to feminine effects of

estrogen

Some supplemented testosterone is converted to estrogen: building bone mass

Double-masked study: men over the age of 65 whose bioavailable T levels were below
normal range, administered 5mg/d for 1 year

Placebo: Femoral neck BMD decreased by 1.6% despite supplementation from Ca

and vitamin D

No significant changes other markers of bone turnover

Increased risk osteoporosis and fracture

T Supplementation: decreased body fat,

increased lean mass, and increased
muscle strength

http://emedicine.medscape.com/article/86659-overview
Testosterones Role in Cardiovascular/Circulatory Systems

Androgens have been reported to have myelostimulating effects

Inducing the production of haematopoietic growth factors in bone marrow

stromal cells

Better iron mobility and bioavailability (T)

Suppresses master iron regulatory protein, hepcidin: biomarker of iron status

Study examined the relationship between endogenous testosterone and
erythropoietic-stimulating agents in men with chronic kidney disease

CKD Patients with T deficiency had 5.3 times greater chance of having anemia
than those with normal T levels

Demonstrated in other patients groups (type 2 diabetes)

Reduced iron availability plays role in decreased erythropoiesis

T levels negatively correlated with haemoglobin

and percentage of hypochromic RBCs

http://www.medical-labs.net/microcytic-red-blood-cell-613/
Role of Testosterone on Infertility
 Basic Causes of:
Varicocele
Infection
Ejaculation Issues
Antibodies that Attack Sperm
Tumors
Testicular Failure
Defects of Tubules that Transport Sperm
Chromosome Defects and Genetic Conditions
Problems with Sexual Intercourse
Certain Medications
Prior surgeries
Environmental and Lifestyle Influences
Obesity
Does Low Testosterone Automatically Mean Infertility?
NO!!

Testosterone is required for sperm production, but

is not the main contributor
FSH and LH
Sertoli cells in the testes support sperm
development
Acted upon by both testosterone and FSH
Leydig cells produce testosterone
Acted upon by LH
The amount of testosterone in the testes is higher
than free blood testosterone
How to Know if Low T is the Cause of the Infertility:
Patient is showing symptoms of low testosterone
An endocrine evaluation is usually suggested when:
Sperm concentration and volume is low
Erectile dysfunction
Hypospermia
Hypogonadism
Evaluation shows assessments of serum FSH and
Testosterone levels
High FSH levels and normal or low testosterone levels imply testicular
failure
Low serum FSH levels and low serum testosterone levels suggest
hypogonadism
When serum testosterone levels are low, the volume of seminal fluid is
usually low
Infertility and Testosterone Supplementation
Testosterone supplements cause
infertility
Negative feedback system
Reversible with time
Exogenous testosterone acts on
both the hypothalamus and
pituitary
Additional Treatments to Allow for Fertility
Intramuscular human chorionic gonadotropin therapy

Selective estrogen receptor modulators

Lets Talk About ERECTILE DYSFUNCTION!!
Erections are androgen dependent
Normal testosterone levels are not necessary for
normal erections
Hypogonadism is the primary cause of endocrine
related ED, but endocrinopathy is the rarest of all
causes
Often due to atherosclerosis
ED and hypogonadism are common in the aging
male, but may not be directly related
Viagra/Testosterone Supplementation for ED
Testosterone therapy was widely used to treat ED until 1998
Some men didn't even have low testosterone
In 1998, Viagra appeared
Current ED medications enhance blood flow to the spongy
tissue
Work more reliably than testosterone and with a quicker
response
Treatment Options
Who Needs Testosterone Replacement Therapy?
Male hypogonadism- testicles are not producing enough testosterone

Primary: the problem originates in the testicles

Secondary: problem with hypothalamus or pituitary gland
Inherited or acquired

Athletes looking to gain a competitive edge

Transdermal Patch
Androderm, Testoderm
2mg or 4mg per day
Application sites: back, stomach, thighs, upper arms
Hormone is released into the bloodstream at controlled rate
Side effect: minor skin irritations (30% of men)
Transdermal Gel
Androgel, Testim
1% or 1.62% concentrations
Individual packets, multi-dose pump, individual tubes
Application sites: shoulder, upper arm, stomach
Testim 1% has greater bioavailability than Androgel 1%
Side effects: minor skin irritations
Risk of transferring between individuals
Oral Undecanoate
Andriol, Androxon
Taken 3 times a day after a meal
Side effects: Gastrointestinal intolerance, suboptimal testosterone levels
Not usually first choice for patients
Enanthate Injections
Most common preparation of testosterone
Aveed, Delatestryl
200-250 mg intramuscularly every 18-28 days
Very safe in terms of undesired side effects
Causes wide swings in testosterone levels
 Other Treatment Options
Testosterone buccal- tablet shaped patch applied to upper gum

Testosterone pellets- implanted under skin

Lifestyle:

Weight loss
Reduce Stress
Eat healthy
Limit or eliminate sugar from diet
Work out
Adverse Effects of Testosterone Replacement
Risk of Cardiovascular morbidity and mortality
Risk of prostate cancer
Lower urinary tract symptoms
Obstructive sleep apnea
Erythrocytosis
Case studies
 Study 1

Patient is a 42 year old male recovering from cancer in both testicles. Both
testicles have been surgically removed. Patient is suffering from increased
physical fatigue, heightened cholesterol, lowered bone density discovered
after recent ankle fracture, experiencing anxiety, and reports feeling down.
Should testosterone supplementation be implemented?
 Study 2
36 year old male visits doctor asking for testosterone supplement. He is
morbidly obese (BMI > 40). He complains of being tired all the time
with lack of libido. He reports a not so healthy diet including fried
chicken, mashed potato and maybe some greens. He reports sleeping
6-7 hours a night, but restlessly. His wife reports that patients snoring is
so loud that he sounds like a motocross bike when he sleeps. Pt history:
patients father and grandfather suffered from prostate cancer. Given all
reported factors, is the patient a candidate for testosterone
supplementation? Why or why not?
 Study 3
A 60 year old male presents signs of hypogonadism and has above normal blood
pressure levels. He is overweight with a BMI of about 30. He has never had heart
problems that he is aware of. He has been trying to lose weight by a diet consisting
primarily of eggs and fish. His main complaint is that he is no longer able to have a sex
life. Is he a candidate for testosterone treatment? Why or why not
 Case Study 4
A 30 year old male is having new medical difficulties. He lives a healthy lifestyle and
had no previous medical conditions. He was recently involved in a motorcycle accident
and received major trauma to his head. Now he lacks energy, has a lowered libido, and
is starting to gain weight at an alarming rate. What happened? How should this be
treated?
Summary/What do we think?

https://www.youtube.com/watch?v=MvtK17hlnfY
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