Testosterone Hormone Therapy with Pellet Implants for Women

Revision of adapted article by Rebecca Glaser MD




Hormone replacement therapy by pellet implantation has been used with great success in the United States, Europe and Australia since 1938 (Greenblatt 49, Mishnell 41, Cantrill 84, Stanczyk 88). Hormonal pellet implants deliver consistent and reproducible effects in relieving symptoms, minimize the fluctuations of hormone levels, and eliminate end organ side effects seen with other methods of delivery (Greenblatt 49, Thom 81, Cantrill 84 Stanczyk 88).  Testosterone implants have additional protective benefits for bone and breast among hormone replacement users.  


Indications for use.


Symptoms of testosterone deficiency/hormone imbalance are often seen prior to menopause. Testosterone pellet therapy alone  is effective for the relief of both physical and psychological symptoms in pre-menopausal and post-menopausal patients. Subcutaneous testosterone therapy is safe and extremely effective for both pre- and post-menopausal patients in relieving “menopausal symptoms” and appears to reduce the risk of breast cancer.

Combination estrogen and testosterone pellets offer excellent relief of menopausal symptoms (Staland 78, Cardoza 84). Testosterone implants have consistently been shown to improve insomnia, sex drive, libido, hot flashes, palpitations, headaches, irritability, depression, aches, pains, and vaginal dryness (Staland 78, Thom 81, Brincat 84, Davis 95, 00, Cravioto 01, Farish 84, Fletcher 86, Sands 97, Seed 00).Women are referred for testosterone supplementation for the following indications:  complaints of emotional lability; fatigue and loss of stamina; impaired concentration and memory; breast tenderness; loss of libido; sleep disturbance; muscle weakness.

Near complete improvement of all menopausal symptoms: hot lushes, heart palpitations, headaches, irritability, lack of concentration, insomnia, depression, dyspareunia, decreased libido, urethral syndrome and lethargy (Brincat, 1984) is achieved with estrogen and testosterone pellet implantation.  Prior the Women’s Health Initiative (WHI)*, women were more likely continue hormone replacement for more than 20 years when combined with testosterone pellets compared to other methods of administration, such as pills, patches and creams (Gambrel 06), despite a moderate incidence of well-tolerated of side effects: breast discomfort 17-18%; increased facial hair 19-22%; acne 2-5%; abnormal bleeding 16% (Cardoza 84). *

Testosterone implant use are found to be more effective than estrogen relief of somatic and psychological symptoms associated with surgical menopause (Sherwin 85). Uninterrupted sufficiency of circulating testosterone supports the production of estradiol by aromatase in estrogen dependent tissues (brain, bone, cardiac, vascular tissue, fat and breast tissue) and affords protection against estrogen deficiency. Also, low circulating levels of estrogen have no bearing on estrogen produced locally. This may explain why continuous delivery of testosterone by pellet implant is so effective in post-menopausal patients, and estrogen only supplementation is inadequate therapy.


Additional benefits of implantable hormone therapy.


Hormones delivered by the subcutaneous implants bypass the liver, do not affect clotting factors and do not increase the risk of thrombosis (Notelovitz 87, Seed 00). Estrogen pellets maintain the normal ratio of estradiol to estrone (Thom 81, Stanczyk 88, Owen 92, Cravioto 01).  Testosterone delivered subcutaneously by pellet implant is cardiac protective, unlike oral, synthetic methyl-testosterone (Sands 97, Worboys 00).


Hormone replacement therapy with testosterone implants has been shown to protect bone alone or in conjunction hormone replacement therapy (Savvas 88, 92, Davis 95, Anderson 97). Consistent and adequate levels of testosterone delivered by pellet implant are essential in maintaining bone mineral density (Aminoroaya 05) The pellets not only prevent bone loss but also actually increase bone density (Savvas 88, Studd 90, Garnett 91, Savvas 92, Naessen 93, Holland 94, Studd 94, Davis 95, Anderson 97, Seed 00, Panay 00).

Testosterone, delivered by pellet implant does not affect the menstrual cycle (Dewis 86) and has been used to treat endometriosis and uterine fibroids (Greenblatt 49). Testosterone pellet implants have also been used to successfully treat severe pre-menstrual syndrome unresponsive to other forms of therapy, without adverse effects (Dewis84).  Additionally pellet therapy has been shown to be effective in the treatment of migraine headaches (Magos 83).

Testosterone delivered by pellet implantation, does not adversely affect blood pressure, lipid levels, glucose or liver functions (Burger 84, Farish 84, Fletcher 86, Barlow 86, Notelovitz 84, Stanczyk 88, Davis 95, 00, Sands 97, Seed 00, Cravioto 01). Estrogen pellets (50 mg) with or without testosterone implants 50 mg) do not cause weight gain, although higher  fat-free mass at 2 years was noted in the testosterone group (Davis 00).

Reduced side effect profile of implantable hormone therapy.

Testosterone acts as a substrate for the production of estradiol (Simpson 02, 03), but delivered by subcutaneous implants does not appear increase the risk of breast cancer (Dimitrakakis 04, Natrajan 02) as does oral, synthetic methyl-testosterone (Tamimi 06).  A reduced risk of breast cancer with estrogen pellet therapy compared to those not receiving treatment (Davelaar, 1991), and the addition of testosterone pellet therapy was shown to reduce the incidence of breast cancer in women treated with conventional hormone therapy.

In breast cancer survivors (n=815), estrogen replacement therapy with pellets did not increase the risk of cancer recurrence or death (Natrajan 02). Unacceptable increased in new breast cancer prematurely ended the 2004 Habits Trial, as study of breast cancer risk with conventional hormone replacement therapy.



Individual treatment doses and treatment ranges are based on  well-established use. Testosterone doses studied in women are as low as 50 mg and up to 225 mg. The most common dose is 100 mg.  In the United States, 75, 100, 110, 125 and 150 mg doses are available. There are generally no signs of androgen excess at these treatment levels, but undesirable side effects may be reduced by lowering the dose.  

Peak serum testosterone levels with the implants are usually seen at one month (Burger 84, Dewis 84, Gambrel 06, Thom 81, Glaser 09) are expected to be between 250 and 375 ng/dl in women. Testosterone implants last between 2.5 and 3.5 months in female patients. Symptoms return when testosterone levels return to pre-treatment ranges (Burger 84, Glaser unpublished).  

Patients commonly receive testosterone implants every 3-5 months alone or in addition to conventional estrogen or estrogen/progestin therapy. The target endpoint is the relief of symptoms in response to testosterone (i.e., relief of depression, increase in bone density, relief from insomnia, lessened anxiety, improved memory and concentration, increased energy, etc.). The testosterone dose is titrated to alleviate symptoms (listed above), improve bone mineral density, and minimize undesirable side effects (facial hair and acne).


Applications for men.

Testosterone replacement therapy in men with subcutaneous implants (pellets) has been shown to be effective, convenient and safe (Handelsman 90, 92, 97, Kelleher 01, 04, Conway 88, Jockenhoval 96, Zacharin 03, Schubert 03, Dunning 04). The routine doses of testosterone delivered by pellet in men is , 1600 and 2000 mg. Therapeutic serum level at one month is 1000-1400 ng/dL in males.  At approximately 4 months, testosterone levels drop at which time symptoms return and the pellets are reinserted.

* After WHI, there was a sharp decrease in hormone use among all HRT, but a larger percentage of women using testosterone pellet with HRT stayed with treatment compared to those not using testosterone (Gambrel 06).