Understanding Hormone Pellet Implants
Introduction
Data supports that hormone replacement therapy with pellet implants is the most effective and the most bio-identical method to deliver hormones in both men and women. Implants, placed under the skin, consistently release small, physiologic doses of hormones providing optimal therapy.
What are pellets?
Pellets are made up of hormones, most commonly either Estradiol or Testosterone. The hormones are pressed or fused into very small solid cylinders. These pellets are larger than a grain of rice and smaller than a ‘Tic Tac’. In the United States, the majority of pellets are made by compounding pharmacists and delivered in sterile glass vials. There is an FDA approved 75
mg testosterone pellet.
Why pellets?
Pellets deliver consistent, healthy levels of hormones for 3-4 months in women and 4-5 months in men. They avoid the fluctuations, or ups and downs, of hormone levels seen with every other method of delivery. Estrogen delivered by subcutaneous pellets, maintains the normal ratio of estradiol to estrone. This is important for optimal health and disease prevention. Pellets do not increase the risk of blood clots like conventional or synthetic hormone replacement therapy.
In studies, when compared to conventional hormone replacement therapy, pellets have been shown to be superior for relief of menopausal symptoms, maintenance of bone density, restoration of sleep patterns, and improvement in sex drive, libido, sexual response and performance.
Testosterone delivered by a pellet implant, has been used to treat migraine and menstrual headaches. It also helps with vaginal dryness, incontinence, urinary urgency and frequency. In both men and women, testosterone has been shown to increase energy, relieve depression, increase sense of well being, relieve anxiety and improve memory and concentration.
Testosterone, delivered by pellet implant, increases lean body mass (muscle strength, bone density) and decreases fat mass. Men and women need adequate levels of testosterone for optimal mental and physical health and for the prevention of chronic illnesses like Alzheimer’s and Parkinson’s disease, which are associated with low testosterone levels.
Even patients who have failed other types of hormone therapy have a very high success rate with pellets. There is no other ‘method of hormone delivery’ that is as convenient for the patient as the implants. Pellets have been used in both men and women since the late 1930’s. There is more data to support the use of pellets than any other method of delivery of hormones. In addition, there is significant data that supports the use of testosterone implants in both women and men.
How and where are pellets inserted?
The insertion of pellets is a simple, relatively painless procedure done under local anesthesia. The pellets are usually inserted in the lower abdominal wall or upper buttocks through a small incision, which is then closed with a skin tape (steri-strip). The experience of the health care professional matters a great deal, not only in placing the pellets, but also in determining the correct dosage of hormones to be used.
Are there any side effects or complications from the insertion of the pellets?
Complications from the insertion of pellets include; minor bleeding or bruising, discoloration of the skin, infection, and the possible extrusion of the pellet. Other than slight bruising, or discoloration of the skin, these complications are very rare. Testosterone may cause a slight increase in facial hair in some women. Testosterone stimulates the bone marrow and increases the production of red blood cells. A low testosterone level in older men is a cause of anemia. Testosterone, delivered by implants or other methods, can cause an elevation in the red blood cells. If the hemoglobin and hematocrit (blood count) get too high, a unit of blood may be donated.
After the insertion of the implants, vigorous physical activity is avoided for 48 hours in women and up to 5 to 7 days in men. Early physical activity is a cause of ‘extrusion’, which is a pellet working it’s way out. Antibiotics may be prescribed if a patient is diabetic or has had a joint replaced. However, this is a ‘clean procedure’ and antibiotics may not be needed.
Why haven’t I heard about pellets?
You may wonder why you haven’t heard of pellets. Pellets are not patented and have not been marketed in the United States. They are frequently used in Europe and Australia where pharmaceutical companies produce pellets. Most of the research on pellets is out of Europe and Australia. Pellets were frequently used in the United States from about 1940 through the late 70’s when oral patented estrogens were marketed to the public. In fact, some of the most exciting data on hormone implants in breast cancer patients is out of the United States. Do men need hormone therapy?
Testosterone levels begin to decline in men beginning in their early 30’s. Most men maintain adequate levels of testosterone into their mid 40’s to mid 50’s, some into their late 70’s to early 80’s. Men should be tested when they begin to show signs of testosterone deficiency. Even men in their 30’s can be testosterone deficient and show signs of bone loss, fatigue, depression, erectile dysfunction, difficulty sleeping and mental decline. Most men need to be tested around 50 years of age. It is never too late to benefit from hormone therapy.
What if my primary care physician or my gynecologist says that there is ‘no data’ to support the use of pellet implants?
He or she is wrong. There is a big difference between ‘no data’ and not having read the data. It is much easier for busy practitioners to dismiss the patient, than it is to question their beliefs and do the research. It’s about a patient making an informed choice. After pellets are inserted, patients may notice that they have more energy, sleep better and feel happier. Muscle mass and bone density will increase while fatty tissue decreases. Patients may notice increased strength, co-ordination and physical performance. They may see an improvement in skin tone and hair texture. Concentration and memory may improve as will overall physical and sexual health. There is data to support the ‘long term’ safety of hormones delivered by pellet implants.
Do pellets have the same danger of breast cancer as other forms of hormone replacement therapy?
Pellets do not carry with them the same risk of breast cancer as high doses of oral estrogens that do not maintain the correct estrogen ratio or hormone metabolites. Nor, do they increase the risk of breast cancer like the synthetic, chemical progestins used in the Women’s Health Initiative Trial. Data supports that balanced, bio-identical hormones are breast protective.
Testosterone, delivered by pellet implantation, has been shown to decrease breast proliferation and lower the risk of breast cancer, even in patients on conventional hormone replacement therapy. Clinical studies show that bio-identical testosterone balances estrogen and is breast protective. This is not true of oral, synthetic methyl- testosterone found in Estratestâ, which gets converted to a potent synthetic estrogen, which can stimulate breast tissue. In the past, testosterone implants have been used to treat patients with advanced breast cancer. In 1940, it was theorized that treating patients with testosterone implants earlier, at the time of diagnosis, would have an even greater benefit, preventing recurrence. Androgens have also been shown to enhance the effect of Tamoxifen® therapy in breast cancer patients. References supporting these statements can be found in the data section of www.hormonebalance.org in the ‘Breast Cancer Folder’.
How long until a patient feels better after pellets are inserted?
Some patients begin to ‘feel better’ within 24-48 hours while others may take a week or two to notice a difference. Diet and lifestyle, along with hormone balance are critical for optimal health. Stress is a major contributor to hormone imbalance and illness. Side effects and adverse drug events from prescription medications can interfere with the beneficial effects of testosterone implants.
How long do pellets last?
The pellets usually last between 3 and 4 months in women and 4-5 months in men. The pellets do not need to be removed. They completely dissolve on their own.
Do patients need progesterone when they use the pellets?
Women who are treated with testosterone implants alone (no estrogen therapy) do not require progestin therapy. However, if estradiol, or other estrogen therapy is prescribed, progesterone is also needed. The main indication for the use of progesterone, is to prevent the proliferation (stimulation) of the uterine lining caused by estrogen. There are progesterone (not progestin) receptors in the bone, brain, heart, bladder, breast and uterus where progesterone has been shown to have beneficial effects. Most of the time, when estradiol is prescribed, progesterone is also prescribed even if the patient has had a hysterectomy.
Progesterone can be used as a topical cream, a vaginal cream, an oral capsule (Prometrium®), or sublingual drops. Only oral progesterone (100-200 mg) and vaginal progesterone (45-90 mg) have been studied and shown to protect the uterine lining from estrogen stimulation.
If a patient is pre-menopausal, she uses the progesterone the last two weeks of the menstrual cycle (day 1, the first day of bleeding). Hormone therapy with pellets is not just used for menopause. Women at any age may experience hormone imbalance. Levels decline or fluctuate contributing to debilitating symptoms. Pellets are useful in severe PMS, post partum depression, menstrual or migraine headaches, and sleeping disorders. Pellets may also be used to treat hormone deficiencies (testosterone) caused by the birth control pill.
Is there a role for testosterone implants (pellets) in a pre-menopausal female?
Testosterone pellets may be used in pre-menopausal females (women who have not stopped menstruating). Testosterone has been shown to relieve migraine or menstrual headaches, help with symptoms of PMS (pre menstrual syndrome), relieve anxiety and depression, increase energy, help with sleep and improve sex drive and libido. If a pre-menopausal female has a testosterone pellet inserted, she must use birth control. There is a theoretical risk of ‘masculinizing’ a female fetus (giving male traits to a female fetus).
Can a patient be allergic to the implants?
Very rarely, a patient will develop local zone of redness (3-8 cm) and itching at the site of the testosterone implant. There is minimal or no tenderness and no other sign of infection. Pellets are made of up testosterone, stearic acid and PVP (povidone). Patients may react to the PVP. Implants can be compounded or made without PVP. Many patients who develop a local reaction to the implant have low cortisol levels and upon further questioning, have symptoms of adrenal insufficiency. Cortisol testing may be recommended. If needed, 25-50 mg of benedryl works well for the itching.
How are hormones monitored during therapy?
Levels will be reevaluated during hormone therapy, usually prior to insertion of the next set of pellets, 4-5 months. After the first year of therapy, hormones levels may be followed less frequently. Men must notify their primary care physician and obtain a digital rectal exam each year. Women are advised to continue their monthly self-breast exam and obtain a mammogram and/or pap smear as advised by their gynecologist or primary care physician.
How much does this cost?
The cost for the insertion of pellets will vary depending on the dose of the hormone and the number of pellets needed. Men need a much larger dose of testosterone than women and the cost is higher. Pellets need to be inserted 2 to 4 times a year depending on how rapidly a patient metabolizes hormones. When compared to the cost of drugs to treat the individual symptoms of hormone decline, pellets are very cost effective. Prevention is much more cost effective than disease. Long, continuous administration of hormones by pellets is convenient and economical for the patient. Pellet implantation has consistently proven more effective than oral, intramuscular, and topical hormone therapy with regard to bone density, sexual function, mood and cognitive function, urinary and vaginal complaints, breast health, lipid profiles, hormone ratios and metabolites.
Research:
Hormone replacement therapy by pellet implantation has been used with great success in the United States, Europe and Australia since 1938 and found to be superior to other methods of hormone delivery (Greenblatt 49, Mishnell 41, Cantrill 84, Stanczyk 88). It is not experimental. Pellets deliver consistent, physiologic levels of hormones and avoid the fluctuations of hormone levels seen with other methods of delivery (Greenblatt 49, Thom 81, Cantrill 84 Stanczyk 88).
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). Bioidentical testosterone delivered subcutaneously by pellet implant is cardiac protective, unlike oral, synthetic testosterone (Sands 97, Worboys 00).
Testosterone and estradiol 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, Handelsman 96, Sands 97, Seed 00, Cravioto 01).
Pellets are superior to oral and topical hormone therapy with respect to relief of menopausal symptoms (Staland 78, Cardoza 84). Estradiol and 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).
Hormone replacement therapy with estradiol and testosterone implants is superior to oral and topical (both the patch and gel) hormone replacement therapy for bone density (Savvas 88, 92, Davis 95, Anderson 97). The consistent, adequate levels of testosterone delivered by pellet implant are important in maintaining bone mineral density (Aminoroaya 05) while also being available as a substrate for the production of estradiol (Simpson 02, 03). 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 implants in women have been shown to improve lethargy, depression, loss of libido, and hot flashes without attenuating the beneficial affects of estradiol on cardiac and lipid profiles (Farish 84, Fletcher 86, Sands 97, Seed 00). Testosterone delivered by subcutaneous implants does not increase the risk of breast cancer (Dimitrakakis 04, Natrajan 02) as does oral, synthetic methyl-testosterone (Tamimi 06). 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 (Dewis 84).
Testosterone, delivered by subcutaneous pellet implant has been shown to improve hot flashes, heart discomfort, sleep problems, depressive mood, irritability, anxiety, physical fatigue, memory loss, sexual problems, bladder problems (incontinence), vaginal dryness, joint and muscular discomfort in both premenopausal and post- menopausal patients without adverse drug events (Glaser 09).
Pellets do not have the same risk of breast cancer as the synthetic progestins or synthetic Methytestosterone. In fact, studies show a reduction in the incidence of breast cancer with the implantation of testosterone pellets, with or without estradiol pellets (Dimitrakakis 04, Tutera 09).
Even after over 20 years of therapy with hormone implants, the risk of breast cancer is not increased (Gambrel 06). In breast cancer survivors, hormone replacement therapy with pellet implantation does not increase the risk of cancer recurrence or death (Natrajan 02) as does estrogen in combination with the synthetic progestins (Habits Trial 04).
Hormone replacement therapy with pellet implantation has an extremely low incidence of side effects (Cardoza 84, Barlow 86, Ganger 89, Pirwany 02) and high compliance rate (Gambrell 06). It has been shown to be extremely effective in the treatment of migraine headaches (Magos 83).
Testosterone replacement therapy in men with subcutaneous implants (pellets) has been show to be extremely effective, convenient and safe (Handelsman 90, 92, 97, Kelleher 01, 04, Conway 88, Jockenhoval 96, Zacharin 03, Schubert 03, Dunning 04).
The testosterone implant is licensed in England for women. The 75 mg testosterone implant is FDA approved in the US (July 13,1972, male patients). Other doses need to be compounded by trained pharmacists. The 75 mg pellet is a sterile product is cylindrically shaped and weighs approximately 77mg (75mg testosterone). The inactive ingredients include 0.2mg stearic acid USP and 2mg polyvinylpyrroidone USP.
The routine doses of testosterone delivered by pellet implantation in recent studies are between 800 and 1200 mg in men. The pharmacokinetics and pharmacodynamics are well established showing that these doses deliver reproducible physiologic levels of testosterone for 4-6 months. The studies show that pellets have a zero order release rate. Although individuals vary, the 75mg testosterone pellet has a consistent release rate approximately 0.5 mg of testosterone per day for a total of approximately 6 mg per day for 12 pellets. A 6-9 mg daily production of testosterone is a ‘physiologic’ level produced by the testicles.
Testosterone implants have a near linear release rate. Peak serum testosterone levels with the implants are usually seen at month one. Therapeutic testosterone levels at month one, are expected at the upper limits of normal for healthy young males (800-1100 ng/dL). By month 4 to 5 testosterone levels drop to below 500-600 ng/dL at which time symptoms return and the pellets are reinserted. Each individual has their own reproducible levels where symptoms return.
Testosterone implants have been used in women. Doses used in studies are as low as 50 mg and up to 225 mg. In the United States, common doses are 75, 100, 110 mg, 125 and 150 mg. There are minimal side effects at these doses (slight increase in facial hair 20% and mild acne 5%), which may be reduced by lowering the dose, if the patient chooses. If measured, serum treatment levels are elevated above non-treatment levels at month one (Burger 84, Dewis 84, Gambrel 06l, Thom 81, Glaser 09). Urine and saliva levels remain normal. There are no signs of androgen excess at these treatment levels. Symptoms return when testosterone levels reach the upper end of endogenous ranges (Burger 84, Glaser unpublished). End organ response to testosterone remains optimal (i.e., relief of depression, increase in bone density, relief from insomnia, relief from aches and pains, lessened anxiety, improved memory and concentration, increased energy, etc.). Testosterone implants last between 2.5 and 5 months in female patients. Individual treatment doses and treatment ranges are established and are reproducible.
In a paper published in the journal ‘Menopause’ in 2004, ‘Breast cancer incidence in postmenopausal women using testosterone in addition to usual hormone therapy’ women were 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
Patients received testosterone implant containing 50-150 mg of testosterone every 5 months in addition to conventional estrogen or estrogen/progestin therapy. The testosterone dose was titrated to alleviate symptoms (listed above), improve bone mineral density and minimize adverse affects (slight increase in facial hair and acne). The most common dose was 100 mg.
Testosterone therapy alone, delivered by pellet implant is effective for the relief of both physical and psychological symptoms in pre-menopausal and post-menopausal patients. Symptoms of testosterone deficiency/hormone imbalance are often seen prior to menopause. Many women begin to experience symptoms by age 35-40, when testosterone production has declined by half (Zumoff 95).
Testosterone alone has previously been reported to be more effective than estrogen/testosterone or estrogen therapy for relief of somatic and psychological symptoms (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.