Chapter 68: Androgens

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Imagine a medication so potent that, while simply tossing a worn t -shirt into a shared family laundry basket, could accidentally send a toddler into premature puberty.

Right, or a drug where just a lingering hug could drastically alter a partner's hormone levels.

Yeah, exactly.

Today we're taking a deep dive into a chemical messenger that doesn't just bind to the outside of human cells, but it actively breaks into the nucleus and just completely rewrites the body's internal playlist.

It really forces us to reevaluate how we think about medication boundaries.

With most drugs, we expect a localized effect, right?

Right.

But with the hormonal powerhouse we're dissecting today, those neat little boundaries simply do not exist.

It touches virtually every system you have.

Which brings us to you, the nursing student listening right now.

Welcome to the deep dive.

We know you are prepping for a major pharmacology exam, and our mission today is to help you master the topic of androgens.

And we are pulling this straight from Chapter 68 of Len's Pharmacology for Nursing Care, the 12th edition.

Yep.

We're going to walk through the chapter in the exact order it's written.

So we're starting with how the body makes androgens, how they work on a cellular level, their therapeutic uses, the major risks, and how to administer them safely.

We want to translate all that dense textbook pharmacology into plain, sticky concepts, so that making safe clinical medication decisions feels like, well, common sense.

Okay, so to understand how to administer these safely, we have to start at the source.

Where are these hormones coming from, and what is their baseline in the human body?

So the testes, the ovaries, and the adrenal cortex all produce androgens to some degree.

But testosterone is the undisputed prototype here.

It's the principal endogenous androgen.

Okay, let's look at the male physiology first.

The ladeg cells in the testes are the main factories here, right?

What kind of production volume are we talking about?

In XY cisgender males, those cells pump out roughly 2 .5 to 10 milligrams of testosterone every single day.

Okay, wow.

That's a lot.

It is.

But that's not a flat line over a lifespan.

Peak production hits around age 17, which makes sense when you think about the massive physiological shifts in puberty.

And then it stays fairly steady until about age 30 or 40, and then begins this slow, inevitable decline.

By the time someone is 80 years old, they're producing about half of what they did during their peak adolescence.

And just to contrast that, for XX cisgender females, the daily production is drastically lower, right?

It's about 300 micrograms a day,

which is, what, 10 to 40 times less than the amount produced in males, and that workload is split pretty evenly between the ovaries and the adrenal glands.

Right, the adrenal cortex specifically.

But here is what always trips me up with hormones.

If I'm producing testosterone right now, how does my body know when I have enough?

How does it know when to shut the factory down?

It relies on a negative feedback loop, and this is controlled by the anterior pituitary gland.

So the pituitary releases follicle stimulating hormone, or FSH,

and luteinizing hormone, LH.

Those two hormones travel down and tell the testes, hey, start making testosterone.

But here's the trick.

As plasma levels of testosterone rise in the blood, that high concentration actually signals back to the pituitary to suppress the release of FSH and LH.

Oh, I see.

So it's essentially like a home thermostat.

Yeah.

That's a good way to look at it.

When the temperature, or in this case, the circulating testosterone, gets high enough, the system tells the pituitary to just shut off the furnace, stop sending the signal.

Then when the hormone levels naturally drop, the furnace kicks back on.

That's a perfect analogy.

The body is constantly chasing that equilibrium.

But let's look at what happens when that testosterone is actually circulating.

How does it physically alter the body?

Most pharmacological drugs you study bind to receptors sitting on the outside of the cell membrane.

They basically ring the doorbell.

Testosterone is entirely different.

Its receptors are located deep inside the cell cytoplasm.

Meaning it just walks right through the front door without even knocking.

Exactly.

It slips right through the cell membrane because it's highly lipid soluble.

So it enters the cell, binds to its specific receptor, and then that new hormone receptor complex migrates all the way into the cell nucleus.

And once it's inside the nucleus, it acts directly on the DNA to promote the synthesis of specific messenger RNA molecules.

Those RNA molecules then serve as templates to create specific proteins.

It's like a VIP guest who completely ignores the bouncer at the club, walks straight into the DJ booth, the nucleus, and just decides to change the entire playlist.

The new proteins being created, those are the new songs playing throughout the body.

Yes, I love that.

And those new proteins are what manifest as the physiological changes we see.

Though there's one nature caveat the text emphasizes here.

In certain key tissues, specifically the prostate, the seminal vesicles, and hair follicles, the receptor doesn't actually interact with testosterone.

It interacts with dihydrotestosterone, or DHT, which is a metabolite that testosterone converts into.

Got it.

I feel like the DHT distinction is going to be incredibly important later when we start talking about prostate cancer and hair loss side effects.

Very important, yes.

But before we get to the adverse effects, let's talk about that new playlist.

First, what are the normal physiological effects of androgens?

In males, increased testosterone drives pubertal transformation.

The physical changes are sweeping.

The testes, penis, and scrotum enlarge.

Pubic, axillary, and body hair appears.

Right, the classic puberty signs.

Exactly.

And it stimulates massive bone and skeletal muscle growth.

It also accelerates epiphyseal closure, meaning it eventually tells the long bones to stop growing in length.

It deepens the voice, ramps up sebaceous gland activity, which triggers teenage acne, and is absolutely essential for spermatogenesis.

Okay, and in females?

In females, endogenous androgens promote clitoral growth and are necessary to maintain a normal libido.

So there is another effect listed in the chapter that just seems kind of out of place for a sex hormone.

The erythropoietic effect.

Yes.

The text says, testosterone acts on the bone marrow to synthesize erythropoietin, which increases red blood cell production.

Is that why men generally have a higher hematocrit level than women?

That is the exact direct mechanism.

Because men have naturally higher baseline levels of testosterone, their kidneys are stimulated to release more erythropoietin, which tells the bone marrow to pump out more red blood cells.

That's wild!

The text actually provides a striking metric for this.

If you give exogenous testosterone to a woman,

her hemoglobin levels will surge by an average of 4 .3 grams per deciliter.

Wait, wow.

Over 4 grams?

That's a huge jump.

It is a massive jump.

But if you give that same dose to a man, his hemoglobin only increases by about 1 gram per deciliter.

Because his system is already, like, maxed out.

Exactly.

Because his system is already near its maximum stimulation from his own endogenous testosterone, you just don't see as dramatic a spike.

...highlight when you are looking at lab values and risk factors, which, well, actually brings us to a major point of confusion.

Oh, the terminology thing.

Yeah.

When we talk about giving these drugs clinically or, you know, seeing them abused, people always divide them into two categories.

They say androgens are for sexual characteristics and anabolic steroids are for building muscle.

Which is probably the biggest myth we need to bust today.

The clinical pharmacology explicitly throws that distinction out the window.

There is no biological difference between an androgen and an anabolic steroid.

Wait,

really?

None.

But athletes take anabolic steroids specifically because they think it targets muscle growth without the other stuff.

They might think that, but the body doesn't work that way.

Both drug types bind to the exact same intracellular receptors.

You absolutely cannot separate the anabolic activity, you know, the muscle building, from the androgenic activity.

Yeah, wow.

They are part of the exact same physiological package.

Because of this, clinical practice has stopped using the two terms and simply classifies them all as androgens.

Okay, so if we aren't categorizing them by what they do, how are they classified?

By their chemical structure.

Group one consists of testosterone and testosterone esters.

Group two consists of the 17 alpha -alkylated compounds, and that second group is notorious for being incredibly toxic to the liver.

Stop right there, because 17 alpha -alkylated is a total mouthful.

What does that chemical tweak actually do to the drug to make the liver hate it so much?

It comes down to basic drug metabolism.

If you were to swallow, cure, and modify testosterone in a pill, it would be absorbed by your GI tract and travel straight to the liver via the portal vein.

Right, the first pass effect.

Exactly.

The liver would look at it and completely destroy it before it ever reached your systemic circulation.

So taking a regular oral testosterone pill is essentially useless.

Pretty much.

So pharmacologists got clever.

They added an alkyl chemical group to the 17 alpha -carbon of the testosterone molecule.

That tiny chemical armor protects the drug.

It survives the first pass through the liver and makes it into the bloodstream.

But I'm guessing that armor comes with a heavy cost.

A very heavy cost.

That specific chemical structure makes the drug incredibly difficult for the liver to process over time.

It creates a metabolic traffic jam, leading to severe hepatotoxicity.

Like how severe?

We're talking colostatic hepatitis, clinical jaundice, and even pedocellular carcinoma, which is liver cancer.

That is why 17 alpha -alkylated compounds should never be used long term.

That makes total sense now.

If the liver is so vulnerable, who else is at high risk?

When we look across a patient's lifespan,

there are some glaring red flags for androgen therapy.

Let's start with pediatrics.

For children, the major risk is virilization and premature epiphyseal closure.

If you give a child androgens, it will fuse the growth plates in their bones prematurely.

So they might shoot up at first, but… Right, they might experience an initial growth spurt, but their final adult height will be permanently stunted.

Wow.

And for pregnant patients?

It is an absolute non -negotiable contraindication.

Taking androgens, especially during the first trimester, causes severe masculinization of an XX fetus.

This manifests as vaginal malformation, clitoral enlargement, and other devastating developmental shifts.

Then we have older adults, and this ties perfectly back to what we discussed earlier about red blood cells, right?

Yes, exactly.

The FDA issued a major safety alert regarding this.

Because testosterone stimulates erythropoietin, it increases red blood cell mass.

In older adults, creating more red blood cells thickens the blood, significantly increasing the risk of thrombosis.

Which means blood clots.

Right.

That thick, sluggish blood leads to strokes, myocardial infarctions, and death.

Because older adults already have a higher baseline risk for cardiovascular events,

testosterone is listed on the BEERS criteria as potentially inappropriate for patients 65 and older.

So hearing all of this, the liver toxicity, the stunted growth, the strokes, what is the actual on -label reason a doctor would prescribe this?

The FDA seems incredibly strict here.

They are very strict.

In 2018, the FDA actually mandated a label change to clarify this.

The only formally approved indication for testosterone is a treatment of confirmed testosterone deficiency due to hypogonadism.

Meaning, the body physically cannot produce it due to a medical failure.

Correct.

It could be primary dysfunction of the testes or secondary failure of the pituitary or hypothalamus.

The FDA was very clear here.

Lower testosterone simply due to normal aging does not count as hypogonadism.

You cannot prescribe it just because a six -year -old man feels a bit sluggish.

So the therapeutic goal in true hypogonadism is replacement.

Restoring libido, supporting secondary sex characteristics, increasing ejaculate volume.

But there is a massive patient education point here for nurses.

Replacement therapy will restore sex drive, but the text specifically notes it will not restore fertility.

No, it won't.

And that is a hard conversation you have to be prepared to navigate with your patient.

Now, even though hypogonadism is the only FDA -approved use, we do see androgens used off -label in several scenarios.

Right.

Sometimes a limited course is used for delayed puberty in boys, usually just to relieve psychological distress if the delay runs in the family.

We also see it used in menopause to relieve fatigue and low libido.

Though the dose there is tiny, around 300 micrograms a day, just mimicking what a pre -menopausal body would naturally make.

Exactly.

Another significant off -label use is gender -affirming therapy for transgender men.

And then there is cachexia, which is the severe muscle wasting we sometimes see with AIDS or massive physical trauma.

Right.

For this, providers sometimes use an androgen called oxandralone.

But the text gives a massive warning about oxandralone.

It can cause something called Pelliosis hepatitis.

Yes, which essentially means the formation of blood -filled cysts inside the liver.

Blood -filled cysts in the liver.

That sounds like a ticking time bomb.

It is incredibly dangerous.

Those cysts can rupture, leading to liver failure or fatal intra -abdominal hemorrhage.

Plus, it causes severe shifts in cholesterol levels.

Let's actually dig into those adverse effects, because they really are just an extension of the physiological mechanisms we covered.

Viralization is the most common complication.

If a cisgender female patient is taking high doses, they might experience acne, facial hair growth, and menstrual irregularities.

But the really scary part is that the voice deepening, clitoral enlargement, and hair loss can be completely irreversible.

Exactly.

As a nurse, you have to teach the patient to stop the drug the absolute second those signs appear.

You also have to monitor their lipid profile.

Androgens are notorious for lowering HDL, the good cholesterol, and elevating LDL, the bad cholesterol.

Why does a sex hormone mess with your cholesterol, though?

Because androgens alter the way the liver synthesizes lipoproteins.

This shift massively accelerates atherosclerosis, which is another reason cardiovascular risk is so high.

Okay, and what about the fluid retention?

I read that androgens can cause serious edema.

Why does testosterone make you retain water?

Think about the molecular structure.

Androgens are steroid hormones.

Their chemical structure is remarkably similar to aldosterone, which is the hormone your body uses to tell the kidneys to hold onto sodium and water.

Oh, I see.

Because of that structural similarity,

androgens cross -activate those pathways, causing the kidneys to retain salt and water.

This is why giving an androgen to a patient with heart failure can be an absolute nightmare.

That makes so much more sense when you trace it back to the mechanism.

Now what about prostate cancer?

Does taking testosterone cause prostate cancer?

No, androgens do not spontaneously mutate cells to cause prostate cancer.

Yes.

However, if a patient already has prostate cancer, even a microscopic undiagnosed covert case,

the androgens will act as high -octane fuel to promote the tumor's growth.

Got it.

So it's an absolute contraindipation.

Okay, I have a practical nursing question.

We talked earlier about kids and premature epithelial closure.

If I have a pediatric patient on androgens for complete hypogonadism, how do I actually know if the drug is fusing their bones before it's too late?

Do I just measure their height and wait to see if they stop growing?

If you wait until they stop growing, the damage is already permanent.

The standard protocol requires radiographic examinations.

You have to take x -rays of the child's hand and wrist every six months.

Every six months.

You are actively looking at the growth plates to monitor bone maturation against their chronological X -rays every six months.

That really underlines how aggressively these medications need to be managed, which leads us to a massive nursing responsibility, how we actually administer the drug.

Right.

Looking at table 68 .2.

Yeah.

If the oral 17 -alpha -alkylated compounds are so toxic to the liver, how do we safely get this hormone into the bloodstream?

That forces us to rely heavily on alternative routes.

Intramuscular injections like testosterone, cypinate, or enanthate are very common.

They avoid the liver's first pass effect entirely.

But the IM injections come with a completely different problem.

They are given deep into the muscle every two to four weeks.

I picture it like a severe roller coaster.

You get the shot, and your blood levels spike way higher than physiological normal.

Right.

Then, over the next few weeks, the levels steadily drop, eventually dipping below normal right before your next scheduled dose.

The roller coaster effect is very real, and the patient feels every dip.

They experience wild, uncomfortable swings in their libido, their energy levels, and their mood.

So, to flatten out that roller coaster, pharmacology gave us transdermal gels.

Brands like AndraGel, Testim, or Fortesta.

The patient applies them daily, and they provide a nice, steady, consistent blood level.

It seems like the perfect solution, right?

For the patient's blood levels, yes.

But it creates a profound hazard for everyone else in their life.

This is the source of the unintended drug transfer safety alert.

This is the laundry basket thing from the intro.

Exactly.

When a patient applies a testosterone gel to their shoulders or upper arms, only about 10 % of that medication is actually absorbed into their skin.

Meaning 90 % of the active hormone is just sitting there on the surface of their skin even after the gel dries.

Yes.

And that residue can easily rub off on anyone they touch.

Skin -to -skin contact, or even touching an unwashed t -shirt, can transfer a massive dose of testosterone.

Wow.

The clinical studies on this are alarming.

In one case, a female partner's blood levels of testosterone doubled after just 15 minutes of intimate contact.

And if it transfers to a child.

Accidental transfer to children causes premature development of pubic hair, genital enlargement, advanced bone aging, and severe aggressive behavior.

This is where nursing education is just critical.

You cannot just hand a patient a tube of gel and send them home.

You have to walk them through the daily routine.

Thoroughly.

Wash your hands with soap and warm water immediately after applying.

Cover the application site with a t -shirt once the gel dries.

If you anticipate skin -to -skin contact with anyone, you must wash the site with soap and water first.

And you have to wait 5 -6 hours before showering or swimming so the initial 10 % actually absorbs.

Also, you need to warn them about Fortesta specifically.

It is an alcohol -based gel,

meaning it is highly flammable until it completely dries.

So no smoking, no open flames.

Okay, well if the gels are too risky for a household with kids, what are the other options?

There is a nasal gel called Natesto.

The patient primes the pump, wipes the gel onto the lateral wall of each nostril, and then they have to refrain from blowing their nose or sniffing aggressively for an hour.

I can't imagine trying not to sniff for an hour with gel in my nose.

What else?

There are also implantable pellets called Testopel.

A provider implants them subcutaneously in the hip or abdomen and they slowly release testosterone for 3 -6 months.

And then there are buccal tablets called Stryon.

Oh, the buccal tablets.

The text had a lot of rules for those.

The buccal tablets are interesting.

The patient pushes the curved side of the tablet against their upper gum right above the incisor and holds it for 30 seconds until it adheres.

But the timing rules are strict.

It's meant to stay there for 12 hours.

If it falls out before 8 hours have passed, you replace it with a new one to finish the 12 -hour cycle.

But if it falls out after the 8 -hour mark… You still put a new one in, but that new tablet counts as your next dose.

You skip the originally scheduled next dose so you don't overload the system.

Stabilizing those blood levels without putting the family at risk is a massive balancing act.

But this discussion of massive doses brings us to the darkest corner of this topic, anabolic steroid use disorder.

Right.

Nearly all androgens are classified as Schedule III controlled substances because the abuse potential is astronomical.

And it spans from junior high locker rooms all the way to professional sports.

Athletes take massive illegal doses to enhance their performance.

And when you look at the raw data, you kind of understand why the temptation is there.

The study cited in the text is wild.

They tracked subjects over a 10 -week period.

The subjects who didn't even exercise but took testosterone gained 7 pounds of muscle.

Just from the drug.

Right.

The subjects who exercised and took testosterone gained 13 pounds of muscle.

And the control group?

The ones who exercised rigorously but didn't take testosterone?

They only gained 4 pounds.

13 pounds versus 4 pounds?

That is an undeniable athletic advantage.

But the biological irony of what happens to these male athletes to get that muscle is brutal.

It really is.

By injecting massive amounts of exogenous testosterone, they trigger that negative feedback lip we talked about earlier.

The pituitary senses all this testosterone and completely shuts off FSH and LH.

The thermostat turns completely off.

And without FSH and LH, the endogenous system goes completely dormant.

The testes shrink.

They stop producing sperm, leading to absolute sterility.

And then there's the gynecomastia, the breast enlargement in men.

Why does that happen?

Because the body tries to manage the massive excess of testosterone by converting some of it into estrogen through an enzyme called aromatase.

Plus, because abusers frequently take the oral 17 -alpha -alkylated compounds, their livers are under constant assault.

The psychological toll is just as heavy, too.

We're talking manic episodes, extreme aggression, and a severe withdrawal syndrome when they try to quit.

Why does an athlete stopping steroids feel like someone coming off opioids?

Because massive steroid abuse alters the brain's dopamine pathways and reward centers.

When they abruptly stop, the brain is deprived of that stimulation, and their natural HBA access is still completely shut down.

They crash into deep depression, fatigue, and intense cravings, which is the hallmark of a true use disorder.

We have covered a massive amount of pharmacology, but let's put this into a real -world nursing scenario using the clinical judgment model.

You are a nurse on a med -served floor.

A 68 -year -old male patient comes in, and his chart shows he is being evaluated for starting transdermal testosterone replacement therapy for diagnosed hypogonadism.

What is going through your mind as you assess him?

First, I am screening his history for absolute contraindications.

Does he have a history of prostate or breast cancer?

I'm looking at his baseline labs, specifically his liver function tests, his lipid panel, and his serum calcium.

Because you know the drug will likely shift his cholesterol and could stress his liver, even though the transdermal route avoids the first -pass effect.

And because he is 68, you are immediately flagging him as high -risk for cardiovascular events.

Exactly.

I am heavily scrutinizing his baseline hemoglobin and hematocrit.

If it's already high, adding testosterone is going to thicken his blood further, risking a thrombotic event.

I also need to ask about his living situation.

Ah, right.

Does he have young grandchildren who hug him frequently?

Does he share a laundry basket with them?

That informs my patient teaching.

And down the road, when he comes back for evaluation at the 3, 6, and 12 -month marks, you are rechecking those lipids, liver enzymes, and hematocrit and ensuring he is getting an annual prostate screening.

It requires meticulous, proactive nursing oversight to keep the patient and everyone around them safe.

Let's step back for a final thought.

We spent a lot of time talking about the unintended drug transfer alert.

Just think about the sheer, quiet power of that mechanism if a lingering hug from someone wearing a medicinal gel can literally trigger premature puberty in a child.

It's terrifying.

Right.

What does that tell us about the skin's massive, often underestimated capacity as an active, highly vulnerable delivery system for the countless other environmental chemicals we touch every single day?

It's a sobering reminder that the skin is not an impermeable wall.

It is a highly active, porous gateway into our bloodstream.

A gateway we need to guard a lot more closely.

Thank you for joining the Deep Dive.

Thank you from the Last Minute Lecture Team, and good luck on your exams.