Testosterone Deficiency, Replacement Therapy & Androgenic Alopecia Pharmacology

Testosterone deficiency: definition

Endocrine deficiency state in which men have a decreased level of testosterone

Hypogonadism symptoms

Depressed mood, low energy, decreased muscle strength and bulk, increased fat mass, impaired cognition, anemia, decreased bone density, fatigue, increased insulin resistance, decreased libido, ED

What does total testosterone measure?

Free testosterone plus bound testosterone

Two categories of testosterone deficiency

Primary: gonadal/testicular failure. Secondary: hypothalamic-pituitary failure.

Labs for testosterone deficiency

Total testosterone, free testosterone, steroid hormone-binding testosterone (SHBG), LH, FSH; plus CBC and fasting blood sugar

Why get a CBC and fasting glucose in testosterone deficiency?

Deficiency can cause anemia and increased insulin resistance

Low testosterone with HIGH LH and FSH suggests

Primary (testicular) failure

Low testosterone with LOW or NORMAL LH and FSH suggests

Hypothalamic-pituitary (secondary) problem; needs further investigation with MRI

How is testosterone deficiency treated?

Exogenous testosterone

Methyltestosterone brand, route, dose

Android; PO; 10-50 mg daily

Fluoxymesterone brand, route, dose

Halotestin; PO; 5-20 mg daily

Buccal testosterone brand and dose

Striant; 30 mg 2 times/day

Testosterone patch brand and dose

Androderm; 2.5-5 mg/24 hr daily, applied to nonscrotal skin

Testosterone cypionate brand, route, dose

Depo-Testosterone; IM; 50-400 mg every 2-4 weeks

Testosterone enanthate brand, route, dose

Delatestryl; IM; 50-400 mg every 2-4 weeks

Testosterone 1% gel brand and dose

AndroGel; 5 g daily, applied to nonscrotal skin

Testosterone pellets brand, route, dose

Testopel; SC; 150-450 mg every 3-6 months

Where are testosterone patches and gel applied?

Nonscrotal skin

Testosterone protein binding

About 98%, to sex hormone-binding globulin

Testosterone absorption by IM route

Complete

Testosterone metabolism and excretion

First-pass liver metabolism with active metabolites; 90% excreted in urine, the rest in feces

Exogenous testosterone clinical uses

Delayed male puberty, male hypogonadism, replacement for endogenous hormone deficiency, male osteoporosis

Testosterone CV adverse reactions

Edema, flushing, hypertension, MI, stroke (CVA), DVT/PE

Testosterone hematologic adverse reactions

Erythrocytosis, polycythemia, suppression of clotting factors, cholestatic hepatitis

Testosterone dermatologic adverse reactions

Acne, hirsutism, male pattern baldness

Testosterone GU adverse reactions

Priapism, testicular atrophy, oligozoospermia (low sperm count)

Testosterone endocrine adverse reactions

Breast soreness, gynecomastia

Testosterone neuro/psych adverse reactions

Aggressive behavior, amnesia, anxiety, depression, nervousness, sleeplessness

Testosterone drug interaction

Warfarin (oral anticoagulants): increased anticoagulant effect and bleeding risk

Testosterone contraindications

Hypersensitivity, male breast cancer, prostate cancer, pregnancy

Testosterone follow-up schedule (history and physical)

Every 3-4 months for the first year, then annually

What if there's no response to testosterone after 3-4 months?

Increase the dose, or discontinue if already at maximum dose

Labs to monitor on testosterone

Lipids, PSA, hematocrit

When to draw testosterone levels for IM injections

Just before the next IM dose (trough), until levels are stable

Monitoring for oral testosterone

Liver function tests every 3-6 months

Which cancers may testosterone stimulate?

Breast and prostate; patients must keep up cancer screening

Which patients need monitoring for erythropoiesis on testosterone?

Smokers, men with vascular disease, men with a history of polycythemia

What to do if hematocrit rises significantly on testosterone

Discontinue the medication

DEA schedule of testosterone

Schedule III (all forms)

Testosterone patient education: expectations

Many deficiency symptoms don't respond to treatment; age and physical condition may limit results

Testosterone gel or patch: risk to others

Pregnant women and women of childbearing age should avoid contact because of possible fetal effects

Conditions testosterone can worsen (need close monitoring)

BPH and abnormal lipid profiles

Vignette: hematocrit rose from 46% to 56% on testosterone cypionate

Discontinue testosterone

Vignette: low testosterone with low LH and FSH

Secondary hypogonadism; order a pituitary MRI

Vignette: patient on warfarin is starting testosterone

Interaction: increased anticoagulant effect, so monitor for bleeding

Male pattern baldness is also called

Androgenic alopecia

Which hormone is linked to male pattern baldness?

Dihydrotestosterone (DHT)

Two medications for male pattern baldness

Finasteride (Propecia) and minoxidil (Rogaine)

Minoxidil original use

Peripheral vasodilator for hypertension (oral form is a third-line antihypertensive)

Minoxidil mechanism for hair growth

Stimulates resting hair follicles into active growth, believed to be from its arteriolar dilating effect

Minoxidil (topical) pharmacokinetics

Not systemically absorbed, so distribution, metabolism, and excretion aren't an issue

Minoxidil drug interactions

None (applied as topical foam)

Minoxidil adverse reactions

Almost none other than local skin effects

Why does Propecia have fewer adverse reactions than Proscar?

Propecia (for baldness) is a much lower dose of finasteride than Proscar (for BPH)

Finasteride for hair loss: effect on PSA

PSA can still be falsely lowered even at low doses; double the PSA

Hair loss meds work best on which area?

Vertex (crown) hair loss; much less effective for frontal and temporal loss

How long until hair loss treatment shows results?

2-3 months for significant improvement; 3-6 months for maximum effect

What happens if hair loss treatment is stopped?

New hair is lost within 4-6 months

Finasteride (Propecia) blood donation rule

Avoid donating blood for at least 6 months after stopping (teratogen risk to a pregnant recipient)

Contraindications for finasteride/dutasteride in hair loss

Hypersensitivity, serious skin reactions to other 5-ARIs, pediatric patients, women who are pregnant or of childbearing potential

Vignette: patient asks if hair loss drugs will help his receding temples

Much less effective for frontal and temporal loss than for vertex loss

Usual cause of epididymitis and orchitis

Bacterial

Epididymitis: likely cause in younger vs older men

Younger: usually an STD. Older: usually E. coli.

What test should be obtained in all cases of epididymitis/orchitis?

Urine culture and sensitivity

Epididymitis/orchitis immediate treatment (per slides)

Ceftriaxone (Rocephin) 250 mg IM single dose + doxycycline 100 mg PO BID for 10 days

Epididymitis treatment if enteric (coliform) organisms suspected

Ofloxacin 300 mg PO BID for 10 days, or levofloxacin 500 mg PO daily for 10 days

Causes of prostatitis

Usually bacterial; viral, fungal, and irritative agents can also cause inflammation

Why is prostatitis treated empirically before culture results?

In older men it can progress to sepsis

Acute prostatitis organism (per slides)

Gram-positive cocci (note: current guidelines say gram-negatives like E. coli are most common)

Acute prostatitis treatment and duration

TMP-SMX twice daily or ciprofloxacin 500 mg twice daily for 4-6 weeks

Which two drug classes in this lecture cause gynecomastia?

5-alpha reductase inhibitors and testosterone

Proscar vs Propecia

Same drug (finasteride). Proscar = 5 mg for BPH; Propecia = lower dose for hair loss.

Drugs in this lecture that can cause priapism

Alprostadil (more common), PDE5 inhibitors (rare), testosterone

Drugs in this lecture that require no blood donation for 6 months

5-alpha reductase inhibitors (finasteride, dutasteride)

Drugs in this lecture that pregnant women should not handle

Finasteride (and avoid contact with testosterone gel or patches)

Lecture objective 6: why do men delay care for these conditions?

Male self-image and stigma make men hesitant to seek care for sexual, urinary, hormonal, and hair-loss problems