Managing testosterone (and its deficiency)

 

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This came up when I searched for “low testosterone”…I don’t think that’s the issue here. 

Very few men are brave enough to ask me, a woman, about “man troubles,” but when they do, I want to give them good counsel.* So, this post is really more like “here’s what I read on the Internet, hopefully it’s a helpful summary”:

Testosterone deficiency. Andropause. Male menopause. Low T. These are the terms your patient may have read about, and they want to know if you think they have it, and furthermore, if you think they need testosterone replacement therapy.

Is testosterone deficiency a real thing?

Short answer: yes, but you have to be strict in how you diagnose it. This is bolded in Up To Date, and whenever something is bolded in Up To Date, it’s important. This Science-Based Medicine article makes a convincing argument that testosterone deficiency has been oversold by the pharmaceutical industry in order to peddle patches, injections, etc. for profit.

What is the range of normal for testosterone in males?

300-1000 ng/dL.

How is testosterone deficiency diagnosed? 

Testosterone deficiency cannot be diagnosed in a single visit. Let me repeat that: it will take at least 2-3 visits/lab draws to make a diagnosis. That’s because testosterone levels fluctuate, and that is a normal thing!

Diagnosis requires repeatedly low morning-level testosterone levels PLUS factors like low libido, loss of morning erections, gynecomastia, loss of body hair, loss of bone density, or small testes.

Vague symptoms, like fatigue, depression, anemia, and loss of muscle strength are NOT enough on their own and should receive a broader workup.

What about in older men? I heard it’s different. 

Kind of? There is no one clear answer. It seems reasonable to treat older men for truly low testosterone levels, like <200 ng/dL who are having symptoms. Data shows that it does improve mood, energy, and sexual function. But there are no big studies of long-term side effects, so if one day it’s found that testosterone secretly causes cancer or dementia, you’ll be glad you were conservative.

Who can NOT receive testosterone?

Patient with severe prostatic hypertrophy, PSA >4.0, history of prostate cancer, erythryocytosis, uncontrolled heart failure. Some people say sleep apnea–this is not totally clear, but may be more of a co-variate. Obesity can lower testosterone levels, and is also associated with sleep apnea.

Before starting anyone on testosterone, make sure to do a prostate exam and PSA level. If the PSA is markedly elevated, you might need to make sure he doesn’t have prostate cancer first…

What are the different kinds of testosterone replacement? 

  • Transdermal: most people consider this the easiest method of administration, but it can be more expensive
  • Injections: can be given every 1-3 weeks depending, but the farther apart the injections are the more labile someone’s symptoms might be
  • Pills are an option, but have been linked with higher rates of hepatic disease
  • Sublingual formulation
  • Nasal gel
  • Subcutaneous implantable pellets (seriously, when there is money to be made, the possibilities are infinite)

What are the side effects of testosterone replacement?

  • Acne: the patch in particular can cause a nasty localized rash, although I think this is more like a contact dermatitis
  • Headaches
  • Hepatitis
  • Polycythemia: rare, but shows up on board questions
  • Fluid retention
  • Hypercholesterolemia
  • Insulin resistance:
  • Infertility: this is not immediately apparent to people, and you should ask your patient if they are planning on conceiving prior to prescribing testosterone. Interestingly, testosterone has been explored as a contraceptive agent.

Labs should be monitored regularly: CBC, LFTs, lipid panel. Testosterone levels can be checked every few months for efficacy, too.

How is testosterone for transgender patients prescribed? Are there any caveats to be aware of? 

Technically, using testosterone for gender transition is off-label. Shameless social justice plug: some friends and I made a document about caring for vulnerable populations, including transgender patients, and you can find more information there.

Testosterone is prescribed in any of the forms described above at similar doses. Many providers will cite “other endocrine dysfunction” instead of “gender identity disorder” or “gender dysphoria” as this is less stigmatizing.

The patient expects to experience deepening of the voice, male pattern hair growth, clitoromegaly, and atrophic vaginitis, among other things. However, breast tissue atrophies less than most people expect. Typical side effects also apply.

* This information is relevant to adults, not to children or adolescents.

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What’s the difference between D2 and D3 for supplementation? And when should you supplement?

I have to look this up myself every time:
D2=ergocalciferol
D3=cholecalciferol

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precisionnutrition.com

One study, albeit small, looked at the effects of vitamin D3 versus D2 supplementation and found that D2 potency is less than 30% of that of D3 and that it has a markedly shorter duration of action. Because the 1,25 form is metabolized in the kidney, D2 is not recommended for patients with CKD or ESRD (D3 should be used). One paper even argues that vitamin D2 should not be sold as a supplement anymore.

Random fact: vitamin D supplementation is a USPSTF grade B recommendation for elderly adults for fall prevention.

Prescribing vitamin D for vitamin D-deficient patients is surprisingly controversial. There are gray areas like what truly counts as “low vitamin D,” racial differences in vitamin D levels (most discussions of vitamin D supplementation are based on evidence in Caucasians), and who should be screened in the first place.

However, here are the quick and dirty guidelines from UpToDate:

Generally, vitamin D deficiency is a serum 25 (OH)D level <20 ng/ml. A couple of specialty societies suggest that a level <30 ng/ml is cause for supplementation in pts >age 65. However people are usually not at risk for osteomalacia unless <10 ng/ml.

Normal adults do NOT need to be screened, but the elderly, those with poor sunlight exposure and malabsorptive disease, should be.

D3 (cholecalciferol) is thought to be more efficacious than D2 (ergocalciferol). Although you will often see someone prescribed 50,000 U weekly followed by 600-800 U daily, there is no evidence behind the 50,000–so you might as well just start them on 600-800 U daily. Vitamin D levels should be monitored every 3-4 months until the target level is met. If someone has malabsorptive disease or isn’t responding to initial treatment, they may require increase of their dose.

What’s the best test to diagnose chlamydia?

Highlights from MMWR:

  • NAAT testing is the gold standard. Who even gets cultures anymore? And serologies are useless.
  • Vaginal swabs are preferred for women; cervical swabs have equal sensitivity. Urine tests may be up to 10% less sensitive but are also specific.
  • For heterosexual men, there are no specific recommendations, but you might as well get it as part of STI screening. First-catch urine samples are superior to clean-catch.
  • For certain populations, such as those who have anal intercourse, a rectal swab is appropriate. An oropharyngeal swab may be appropriate, too, especially in prepubescent girls or children who have been sexually assaulted; also in those with suspected treatment-resistant gonorrhea because of the rates of co-infection.

What regimen can I give a patient going through opiate withdrawal? 

This is the typical cocktail our psychiatry consultants recommend:

  • Robaxin 500-700 mg q6h prn muscle cramps
  • Bentyl 50 mg prn abdominal pain
  • Clonidine 0.1 mg prn anxiety, hold for systolic blood pressure <90
  • Hydroxyzine 50 mg q6h prn anxiety or insomnia
  • Kaopectate prn diarrhea

Always make sure to check a tox screen to make sure they’re not going through concurrent alcohol or benzo withdrawal!

What does a urine tox screen test for? (And how do you interpret the results?)

The urine tox screen is one of the most superficially helpful tests we have. At first glance it seems like a simple “yes/no” answer. I mean, either someone did or didn’t take heroin…or did they? It turns out there is a lot more gray in interpreting the results of a urine tox screen, and it’s important to take your time thinking about the results lest you condemn someone unfairly–or let them get away with abuse.

When should someone be screened? 

It’s possible to stratify patients into high-risk and low-risk abusers but you really should screen everyone who is on a potential drug of abuse. Definitely at the first appointment, and then 2-3 times/year has been shown to be effective. If you are changing a patient’s dose substantially, or if they have more complaints about decline in function, that may be a good time as well.

Which is better, the urine or serum tox screen?

Actually, it’s urine. According to Path Group:

Drugs of abuse can be detected in urine for days to weeks after exposure, in contrast to blood detection which is generally in hours. For example, heroin has a half-life of 6 to 15 minutes in blood, but opiate metabolites may be detected in urine for 2 to 3 days.

Is it possible to get false positives on a urine tox screen?

Yes. One factor is individual pharmacokinetics. There are genetic differences in CYP450 enzyme activity, and if patients are on other CYP450-metabolized medications, they could have different levels of processing medications like opiates. Other factors include whether the patient is obese, what dose they are taking and how frequently, and more.

If you are concerned that there may be a false positive, order confirmatory testing with GC/MS (gas chromatography/mass spectrometry). This is highly specific and reliable.

Opioid Risk has a great summary of what could cause different “false positive” or “false negative” scenarios. (Go to “Interpreting Test Results” on page 5)

Here is a list of some caveats from HealthPartners:

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If a substance is detected, can you tell how long ago it was taken? (Reference)

Substances are detectable for a certain range of time, and the specific times may depend on your institution’s lab.

  • Alcohol 7-12 h
  • Amphetamine 48 h
  • Methamphetamine 48 h
  • Barbiturate Short-acting (eg, pentobarbital) 24 h
  • Long-acting (eg, phenobarbitol) 3 wk
  • Benzodiazepine Short-acting (eg, lorazepam) 3 d
  • Long-acting (eg, diazepam) 30 d
  • Cocaine metabolites 2-4 d
  • Marijuana Single use 3 d, Moderate use (4 times/wk) 5-7 d, Daily use 10-15 d, Long-term heavy smoker 30 d
  • Codeine 48 h
  • Heroin (detected as morphine) 48 h
  • Hydromorphone 2-4 d
  • Methadone 3 d
  • Morphine 48-72 h
  • Oxycodone 2-4 d
  • Propoxyphene 6-48 h
  • Phencyclidine 8 d

What substances will NOT be detected by urine or serum tox screening? [I’ll try to update this as I get more info] 

  • fentanyl

What are some ways that people try to thwart tox screening? 

The length of time a drug can be detected in the urine varies due to several factors, including hydration, dosing, metabolism, body mass, urine pH, duration of use, and a drug’s particular pharmacokinetics.

  • Someone may try to make a drug level “undetectable” by drinking tons of water to dilute their urine. Conversely, someone may try to make it seem like they do have an appropriate level of a prescription drug by dehydrating themselves to concentrate the urine.
  • This has actually happened: someone buys “clean” urine off the street and passes it off as their own during drug testing. This is why some institutions require supervised urination. There are ways to check for this, like temperature-sensitive cups, measuring the specific gravity of the sample, or creatinine concentration (these will all be different in stagnant urine that has not recently exited the body).
  • This is not “thwarting” per se, but if a patient is on a low dose or has long intervals between doses, they may have a false negative because the concentration of drug is below the cutoff on the assay.

 

True or false: “I had the BCG vaccination so I need to get a chest x-ray instead of the PPD”

False! Employee health workers may say that people who have gotten the BCG vaccination–usually from Asia, Africa, or the Caribbean–do not have reliable PPD readings and therefore need chest x-rays. One magazine article reports: “Current Occupational Safety and Health Administration (OSHA) regulations do not require periodic chest x-rays for a health-care worker who is PPD-positive unless symptoms develop.”

Furthermore, according to Ethnomed:

“Prior vaccination with BCG is not a contraindication to TB skin testing, and the CDC guidelines recommend ignoring BCG status when interpreting skin test results and selecting candidates for latent TB treatment. Although BCG vaccination can turn a skin test positive, reactivity due to BCG vaccination wanes over time. If it has been more than 5 years since vaccination, a positive skin test is more likely due to TB infection than vaccination. Furthermore, the larger the size of the PPD reaction, the less likely it is due to BCG. A recent meta-analysis found that reactive skin tests more than 15 years since vaccination or with more than 15 mm of induration were unlikely to be due to prior BCG vaccination.

Interferon-based blood tests such as the QuantiFERON® -TB Gold avoid the possibility of false-positives occurring from BCG vaccination, since cross-reactivity does not occur.”

Be warned that the Quant Gold may come back as “indeterminate” or “borderline” and then you may be in a bit of a pickle and have to get a chest x-ray anyway.

Questions you should make sure to ask someone who has had a past positive PPD:
1. How long ago was it?
2. Have you ever received the BCG vaccine?
3. Did you ever receive treatment for latent TB? (isoniazid)
4. Have you ever had a chest x-ray previously?