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Testosterone Replacement in Female Chronic Pain Patients

Since testosterone assists opioids in crossing the blood brain barrier and helps activate a number of central receptors and neurochemicals systems, it is a judicious, ethical, and clinically necessary practice to replace testosterone in female chronic opioid patients—subject to informed consent.
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Testosterone suppression is well known to occur in chronic pain patients who must regularly take opioids.1-2 Replacement of testosterone in male chronic pain patients is now commonplace. To date, however, testosterone replacement in female chronic pan patients is not routine and practitioners are just beginning to recognize the needs and merits of doing so.3-4

Reported here is the female testosterone replacement procedure used by the author. A patient education handout and an off-label consent form is included which practitioners may adopt if desired. Since there is no commercial FDA-approved testosterone product for females, physicians should systematically prescribe testosterone to female patients by diligently providing information about risk-benefit and carefully documenting a need for testosterone replacement.

Symptoms of Testosterone Deficiency

Pain patients who are being routinely followed may slowly but progressively develop testosterone deficient symptoms (see Table 1). While loss of libido is the best known of testosterone deficiency symptoms, there are many others.5 Testosterone has some critical biologic functions very relevant to pain treatment.6-8 Testosterone is a major anabolic compound both in females and males and, therefore, has a major healing and pain reduction function in long-term pain care.4 Testosterone levels are apparently necessary for proper transport of opioids across the blood brain barrier and for opioid receptor-site binding.6-8 Consequently, adequate levels of serum testosterone are necessary for maximal opioid effectiveness. Other central effects are more subjective, but testosterone deficiency is associated with depression, fatigue, apathy, and loss of motivation.

Patient Education

Females, as well as males, need to be educated about the need for adequate serum levels of testosterone. Table 2 presents an educational handout which can be given to all female pain patients. Since testosterone replacement in females is a new procedure and obviously controversial, it is deemed important that practitioners educate all parties on the benefits and necessity of testosterone replacement. Many parties are not even aware that females normally carry a serum concentration of testosterone that is about 15 to 25 % of that in the male. Furthermore, adequate serum testosterone levels in female pain patients is critical for maximal pain control.

Stepwise Guidelines for Replacement

If symptoms of testosterone deficiency are present in a female chronic pain patient, obtain a serum testosterone concentration. Laboratories now report normal ranges for serum testosterone in females as well as males. If the female patient demonstrates a low or borderline low level, I give a test dose of intramuscular testosterone ranging from 25 to 50 mg. This test dose is usually therapeutic within 24 hours, as female patients with testosterone deficiency rapidly experience a number of positive benefits as symptoms of testosterone deficiency are ameliorated.

Table 1. Some Symptoms of Testosterone Deficiency
  • Lack of energy
  • Loss of libido
  • Depression
  • Poor healing
  • Diminished opioid affects
  • Loss motivation
  • Apathy
Table 2. Sample Patient Education Handout
Testosterone Information For Female
Chronic Pain Patients
One of the major complications of intractable pain and opioid treatment is a decline in body testosterone levels.
The symptoms of low testosterone, in women and men, are as follows:
  1. Fatigue
  2. Depression
  3. Opioid medication less effective
  4. Decrease in libido
  5. Loss of motivation and interest in life
  6. Poor healing
If you are experiencing the above symptoms, you should have your testosterone blood level checked. This is done by a single blood test taken at anytime of day. The laboratory will determine if you are deficient.
If you are deficient in testosterone, you will be given a low, test dosage of testosterone to determine if your symptoms are caused by testosterone deficiency. If your symptoms improve, you will need a course of testosterone. The dosage you will receive is a fraction of the male testosterone dosage.
After you have taken testosterone for a few weeks, your blood level of testosterone will again be tested to determine if you need to continue it.
At this time, there is no known risk to taking a low dose of testosterone providing your body is deficient. Although, no risk is known to occur in female pain patients who take low dosages of testosterone, it is recommended that you do not take testosterone every day and periodically (e.g., every 3 months) stop taking it for a few days.

Once testosterone deficiency is documented, the patient is asked to sign an informed consent form for off-label use of testosterone (see Table 3). I use a testosterone gel (Testim® or Androgel®) at 1/3 to 1/2 the male dosage. Initially, the patient rubs on the gel every other day. This dose can be titrated upward over time. At the end of about 90 days, I repeat the serum testosterone test and require a one week break. If symptoms recur and the serum level is still low, I continue the testosterone.

The reduction and amelioration of testosterone deficiency symptoms is often remarkable. At this early phase of female testosterone treatment, I have not witnessed complications or long-term side-effects.

Laboratory Testing and Interpretation

All major clinical laboratories now test for total and free serum testosterone. They will report their normal values for sex and age which makes it easy to diagnose hypotestosteronemia.

At this time there is a raging debate among some endocrinologists and urologists as to the meaning of serum free and total testosterone and sex hormone binding globulin. The issue stems from the fact that most (over 80%) of serum testosterone, is bound to serum proteins including sex hormone binding globulin. Some experts believe that only about 1% of serum testosterone is “active,” due to the protein/globulin binding nature of testosterone. They even argue that the remaining protein-bound testosterone is irrelevant and apparently some sort of biologic waste product. At this time, it is recommended that pain practitioners let the testosterone debates rage on and simply use laboratory-reported serum levels of free or total testosterone in combination with clinical symptoms as the reason to initiate a low dose clinical trial.

Last updated on: May 9, 2014
First published on: November 1, 2009