provides additional, and much needed, safety data pertaining to postmenopausal testosterone use. It is important to note that the implantation of E2 pellets is not recommended at present as estrogen requires careful titration in because of the narrow optimal benefit/adverse reaction margins in some women. Pellets do not allow for this in a timely manner. Therefore transdermal or transvaginal estrogen is preferred instead of E2 pellets. In addition, testosterone is the major substrate for E2. Aromatase, at the cellular level, provides adequate amounts of E2 to the estrogen receptor. Serum levels of E2 do not accurately reflect end organ function.
Hormone Implants and Breast Cancer
What about testosterone implants and breast cancer? First and foremost it is important to stress that bioidentical testosterone delivered by pellets does not increase the risk of breast cancer, and that treatment with testosterone and E2 implants does not increase the risk of breast cancer. In fact, studies investigating testosterone implants suggest less stimulation of breast tissue and a reduced risk of breast cancer.7-9
Pellet Dosing Options
Men
The dosage range is 800-1800 mg. My average starting dose in men between 175-200 lbs is 1400-1500 mg. For men <175 lbs the average starting dose is 1200 mg. For the lightweight elderly man (<150 lbs) the starting dose should be 1000-1100 mg or less and titrated upwards. Consider a starting dose of 1500-1700 mg for men 200 lbs or heavier.
We find that men are much more conscious of achieving substantial benefits than women are, so in my practice it is common to given generous doses to men and then titrate back down if needed, for example if metabolite levels (E2 and DHT) become elevated, or if the patient start to experience aggressiveness, severe acne, or prostate symptoms. However, this is very uncommon.
Women
My average starting dose is women is 100 mg regardless of weight and titrate upwards based on response and follow-up labs. Note: Some elderly women actually need a higher dose. Dosage range is 70-150 mg. Women are much more emotionally and physically sensitive to too high testosterone levels (if facial hair growth and acne is excessive) thus it is far better to start low and work up. It is important to inform female patients that you are starting on a low dose as they will feel more comfortable.
New Options for Testosterone Implantation
Testosterone therapy has documented benefits in both men and women’s health. However, increased or aberrant aromatase expression (age, obesity, medications, diet, breast cancer, prostate cancer, etc.) and subsequent elevated estradiol can interfere with testosterone’s effectiveness. In addition, there is increasing evidence of the adverse affects of elevated estradiol on prostate, breast, uterus, obesity, metabolic syndrome, and mood.
To prevent these side effects, compounding pharmacists have combined testosterone with anastrozole, an aromatase inhibitor. In an email with Dr. Rebecca Glaser (September 7th, 2011), she wrote: “The biggest difference in my practice now versus when I trained you (2008) is that I am using an aromatase inhibitor much more frequently. We combine testosterone with anastrozole in a pellet implant. It works great. Men increase aromatase activity as they age. Interestingly, 70% of men on pellets do better with the combination. If a male patient isn't doing well on pellets it is almost always estrogen related (aromatization to E2).”
Combining testosterone with anastrozole is:
•Best for men with high-normal or high E2 prior to treatment (usually obese);
•Best for women with active breast cancer;
•Optional for women for whom any estradiol elevation would be undesirable (already elevated levels prior to treatment with HRT, strong FH of breast cancer, obesity with high normal E2 levels prior to treatment.
At the 9th European Congress on Menopause and Andropause (EMAS 2012) in Athens Glaser and Dimitrakakis10 presented a poster of their 2 year record of testosterone/anastrozole (T/A) implantations. They reported that:
•Female indications for using aromatase inhibitor therapy included: a history of breast cancer or increased risk for breast cancer, breast pain, fibrocystic breast conditions, endometriosis, uterine fibroids, dysfunctional uterine bleeding, weight gain, increased abdominal obesity, insulin resistance with elevated estradiol, menstrual or migraine headaches, PMS, anxiety, irritability, aggression, fluid retention, and bloating;
•Male indications included: history of prostate cancer or benign prostatic hyperplasia (BPH) (8%), elevated E2 prior to or on testosterone therapy (86%), and symptoms alone (6%) which include: lack of effect from therapy, fluid retention, bloating, anxiety, irritability, excess aggression, abdominal obesity, weight gain, gynecomastia, and breast pain or enlargement
A chart review of 1,408 T/A pellet insertions performed between July 2009 and July 2011 was also presented (Fig. 1). Insertions were performed on men and women either with testosterone-only or T/A combination pellets.as a sustained-release pellet implant. Results showed that T/A pellets provided therapeutic levels of testosterone without elevating E2 in both men and women, and that E2 levels in the those treated with T/A pellets were significantly lower (P<0.0001) than in those treated with testosterone-only.
Figure 1. Dr. Rebecca Glaser’s 2-year record of testosterone-anastrozole implantations.
According to Yogesh Bhakta PharmD (personal communication) he believed that the ideal combination of testosterone and anastrozole would be 60 mg testosterone and 4 mg anastrozole 4mg pellets. Thus a man needing 1200 mg of T/A pellets would use: 4 x 60 mg/4 mg T/A pellets and 960 mg of testosterone-only pellets. A woman might use 2 of these pellets (120/8). Both T/A and testosterone-only pellets are available from multiple pharmacies.
Retesting Testosterone Levels
Testosterone levels should ideally be retested 1-2 months (peak levels) post implantation. Trough levels should also be determined at 4-months for men and 3-months for women. Patients using cream should be tested 24-hours after application, and those receiving injections should be tested 3-4 days post injection (or 2-days for peak and 6-days for trough).
Of course there are several methods for determining testosterone levels – saliva, blood spot, or bioavailable levels in venous blood. Dr. Pam Smith (Director of Fellowship Training, American Board of Anti-Aging and Regenerative Medicine) advises saliva or blood spot testing (instead of venous blood) as these methods measure tissue/cellular levels of testosterone. If you choose to use venous blood it is important to order testing for bioavailable testosterone (free plus weakly bound). Many physicians find that with male patients they seem to find a better correlation between clinical response and serum bioavailable testosterone levels than with blood spot or saliva, however if you are using saliva or blood spot and find good clinical correlation between the results and the patients clinical status there is no reason to use venous blood.
As well as retesting testosterone it is also important to monitor PSA, ultrasensitive E2, and DHT (in venous blood). It is also prudent to order a complete blood count (CBC). Testing should be repeated after each implantation for the first year and until stable, and then annually or more often depending upon individual circumstances.
