Testosterone Replacement Therapy (TRT) and BPH

hypogonadism

failure of testes to produce physiological levels of testosterone due to disruption of HP-Testicular axis

primary hypogonadism

low testosterone (T)

elevated gonadotropin

secondary hypogonadism

low T, low-normal gonadotropin

mixed hypogonadism

low T

variable gonadotropin

Mixed hypogonadism is most commonly scene in ...

males > 40yrs

aka andropause or male menopause

requirements for hypogonadism diagnosis

two total testosterone levels drawn in morning

T levels < 300ng/dL

when is free testosterone measured instead of total testosterone

whne total T concentrations are near lower limit of normal range (200-400)

When is testosterone highest?

morning

Goals of TRT

improve/alleviate symptoms of hypogonadism, minimize ADEs of TRT

restore normal serum T levels

what is goal T level?

there is no specific goal, but typically aiming for >300ng/dL

what symptoms are hoped to be alleviated with TRT?

decreased libido

ED

testosterone products

oral

transdermal

buccal

nasal

IM, SQ

SQ implant

Testosterone products are schedule ____ controlled substances

schedule III

BBW of testosterone products

gels/topicals: risk of secondary exposure

undecanoate injection: POME reactions

oral/SQ undecanoate: increased BP

T products are contraindicated in ...

men w/ prostate cancer

pregnant/breastfeeding women

caution/warnings with T products

avoid T in men w/ recent MI or stroke (last 6mo)

avoid T products in men w/ severe lower UTIs

ADEs of T products

increased PSA

Polycythemia (increased HCT)

fluid retention (BP, worsening HF)

hyperlipidemia (↑TG, ↓HDL)

increased LFTs

low sperm

gynecomastia

this formulation of T has hepatotoxicity potential

oral formulations

labs to obtain before initiating TRT

hematocrit

PSA

timeframe of TRT monitoring

baseline --> 1-3mo --> 6-12mo

what is monitored at baseline before TRT?

T levels

CBC (incl. HCT)

PSA

liver function

lipids

BP

what is monitored at 1-3mo of TRT

T

CBC

PSA

symptoms of low T

ADEs

liver function

lipids

BP

monitoring at 6-12mo for TRT

same as 1-3mo

TRT should NOT be initiated IF:

prostate/breast cancer

PSA >4ng/dL (or >3 & high risk of prostate cancer)

severe LUTS

erythrocytosis (HCT >48%)

untreated severe OSA

uncontrolled HF

recent (<6mo) MI or stroke

hypercoagulable state (clots)

counseling for testosterone gel

apply to appropriate area based on product

cover application to avoid accidental exposures

avoid swimming, showering, etc. for 2hrs

counseling for testosterone patch

apply to clean, dry area on abdomen/back/upper arms/thigh EACH NIGHT

allow 7days before reapplying to same spot

avoid swimming, showering,etc for 3hrs

If patch falls off before noon ...

apply new patch

do not replace if it falls off after noon, wait until fresh patch that evening

TRT should be discontinued if:

PSA increase by >1.4ng/mL from baseline

PSA >4.0mg/mL

HCT >54%

can TRT be restarted once Hct returns to safe level (<48%)

yes

TRT products used for masculinizing therapy in transgender men

any T product may be used; all are used off label for this purpose

dosing for masculinizing therapy in transgender men

initial dosing as labeled for hypogonadism

BUT

higher doses may be needed to suppress female characteristics

for transgender men receiving TRT, what reference range is used for HCT?

male reference range

obstructive symptoms of BPH

prostatism or bladder outlet obstruction symptoms

urinary hesitancy

urinary straining

weak stream

constant feeling of bladder fullness

over distention of bladder

irritative symptoms of BPH

urinary frequency and urgency

nocturia

typically occur later in disease

treatment of obstructive BPH symptoms

alpha blockers

5AR

PDE5i

treatment of irritative BPH

anticholinergics

beta3 agonists

LUTS

lower urinary tract symptoms

both obstructive and irritative BPH symptoms are considered LUTS

diagnosis and classification of BPH

international prostate symptom score (IPSS)

mild BPH

IPSS 0-7

moderate BPH

IPSS 8-19

severe BPH

IPSS 20-35

Important information to obtain upon BPH diagnosis

current Rx/OTC meds

DRE (assesses prostate size)

voiding diary

urinalysis (rule out other conditions)

PSA blood test

bladder emptying/PVR urine study

reported symptoms

mild IPSS score (LUTS) calls for ...

watchful waiting

recommended drug for Moderate/severe LUTS with prostate <40g OR PSA ≤1.4

alpha1 blocker

alpha1 blockers used for BPH

Tamsulosin

silodosin

drug recommended for mod-severe LUTS w/ prostate >40g OR PSA >1.4

5alpha reductase inhibitor

+/- alpha1 blocker

5alpha reductase inhibitors used for BPH

finasteride

dutasteride

dutasteride + tamsulosin

first line for mod-severe BPH symptoms w/ ED

PDE5i

+/- alpha1 blocker and can add 5alpha reductase inhibitor

recommended therapy for BPH with predominantly irritative symptoms

beta3 agonists or anticholinergic should be added to alpha1 blocker +/- 5alpha reductase inhibitor

tamsulosin dose

0.4-0.8mg PO daily

silodosin dose

8 mg QD

ADEs of tamsulosin and silodosin

less hypotensive effects than non-selective alpha1 inhibitors (prazosin, etc)

ejaculatory disorders

safety monitoring for alpha1 blockers

ADEs (BP, HR, orthostasis)

ejaculatory dysfunction (selective agents)

floppy iris syndrome (cataract surg. pts.)

most useful monitoring when deciding to change alpha1 blocker dose

LUTS improvement

counseling with IR non-selective alpha blockers

-slow titration minimizes orthostatic hotn

-take at bedtime

-increase dose weekly depending on response (LUTS)

why are ER alpha blockers preferred over IR?

no titration necessary

less hotn

once daily dosing

efficacy/safety monitoring following any med change should be assessed when?

within 6-12 weeks

MOA of PDE5i for BPH

improve obstructive and irritative symptoms

preferred in pts with BPH and ED

PDE5i used for BPH

tadalafil

tadalafil dosing (+ renal considerations) for BPH

5mg PO once daily

2.5mg daily if CrCl 30-50 (do not use if <30)

ADEs of tadalafil

flushing

headache

myalgia

back pain

vision/hearing loss

function of 5alpha reductase

converts testosterone to DHT which triggers growth factors

5alpha reductase inhibitors are typically reserved for BPH patients with ....

enlarged prostates (>40g) +/- PSA >1.4ng/mL

finasteride dosing

5mg PO daily

dutasteride dosing

0.5mg PO daily

ADEs of 5alpha reductase inhibitors

ED

decreased libido

ejaculatory dysfunction

gynecomastia

5⍺Ri efficacy monitoring

PSA reduction

improved BPH/LUTS symptoms after 6-12mo

measure new PSA 6+ months after initiation

safety monitoring for 5⍺Ri

ADEs of medications

people who are pregnant or who wish to become pregnant should not TOUCH these drugs

how long is treatment with 5⍺Ri necessary?

6-12 months for efficacy to be seen

medication will reduce PSA values by ~50%

beta3 agonists

mirabegron

vibergon

mirabegron dosing

25-50mg po daily

max dose 25 for eGFR 15-29

ADEs of beta3 agonists

increased BP

tachycardia

GI effects

dizziness, headache

beta3 agonists monitoring

BP/HR

med ADEs

urinary symptom improvement

anticholinergic agents used to treat irritative symptoms of BPH

oxybutinin

tolterodine

trospium

darifenacin

oxybutinin dosing for BPH

5-10mg PO BID/TID

XL: 5-30mg PO daily

1 patch twice weekly

ADEs of anticholinergics

dry mouth

constipation

blurred vision

tachycardia

dizziness, drowsiness, confusion

acute urinary retention

MOA of anticholinergics for BPH

relax bladder detrussor muscle --> increasing bladder storage

muscarinic receptors found in the bladder

M2-M4

anticholinergics are not preferred in this patient population

elderly (CNS effects)

M3 selective inhibitor

darifenacin

might be more tolerable for elderly patients

avoid anticholinergics in patients with ...

high post-void residual volumes

anticholinergics are contraindicated in patients with ...

narrow angle glaucoma

decreased urinary/intestinal motility

anticholinergic therapy should be re-evaluated at ...

4-6 weeks of therapy

monitoring for anticholinergics in BPH pts

changes in mental status

med ADEs

urinary symptom improvement