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Why Do So Many Menopausal Patients Prefer Estrogen Hormone Pellets for Hormone Replacement Therapy?


Menopausal Patients Prefer Estrogen Hormone Pellets for Hormone Replacement Therapy

Why Do So Many Menopausal Patients Prefer Estrogen Hormone Pellets for Hormone Replacement Therapy?

By Dr. Edouard Servy|August 29th, 2018|

Hormone pellets are an effective hormone replacement therapy (HRT) method for treating menopause symptoms. Natural, bioidentical hormone pellets mirror the estrogens produce by the body and can be a great option for women who have not experienced relief from menopause symptoms with other forms of HRT.

We provide patients interested in estrogen pellets with a number of educational resources so they can learn more about the science that makes hormone pellets an effective treatment option for menopause. Following are some of the frequently asked questions our patients have about methods of hormone replacement therapy, including use of hormone pellets, which the majority of our patients undergoing long-term HRT find more appealing.

1. What are the different sources of estrogen?

Natural estrogens are those produced by the human body. The ovaries secrete them directly into the bloodstream. They are also called bioidentical, a term mainly used in advertisements to make it sound more scientific, but the original scientific term is natural estrogens. There are three natural estrogens: estradiol, estrone and estriol. The only one that is directly active on human tissue receptors is estradiol. The two others, estrone and estriol, are precursors for different hormones and they have no therapeutic value. So when someone advises you to use a compound (cream or gel) that contains the three estrogens, either he doesn’t know his pharmacology or he is trying to complicate the issue.

Estradiol, estrone and estriol can be easily measured in blood, but estradiol is the only one needed to evaluate a therapeutic effect. Usually, the sources of these natural human forms of ovarian hormones are the building blocks found in wild yams and soybeans. The laboratory converts these plant compounds into chemical molecules identical to those made in the human body for 17-beta estradiol, progesterone or testosterone.

Conjugated estrogens are equine estrogens, extracted from the urine of a pregnant mare. They contain 10 estrogenic components, the main ones being estrone sulfate and equilin sulfate. Conjugated estrogens are available in preparations directly obtained from the mare’s urine (Premarin) or they can be fully synthetic replications of the equine preparations.

Premarin inexplicably has been the most commonly prescribed or used estrogen in the United States and Canada for a long time. Premarin can sometimes treat menopausal symptoms but it is not natural for human consumption. Its effects can be evaluated on target tissue but cannot be measured in the blood and have been implicated in association with Provera (medroyprogesterone) in the unfavorable results of the Women’s Health Initiative study.

Ethinyl estradiol is another synthetic derivative of estradiol found mainly in birth control pills. It’s not measurable in serum. It’s always associated with synthetic progesterone in order to provide contraception. This combination improves the bioavailability and makes it more resistant to metabolism, showing increased effects in the liver, which is good for the contraceptive effect but not good for the liver.

Conclusion: Estradiol is the only natural and efficient estrogen and it’s available in many forms. It can be checked in blood or saliva, but the measurements are much more reliable in blood than in saliva.

2. What are the different ways of administering estradiol?

In determining whether drug therapy is an appropriate treatment, a provider analyzes a medication’s safety, efficiency and whether it is well tolerated. Its intake must be convenient, and its effects measurable and predictable. The patient must be compliant. Finally, the cost must be reasonable and affordable in order to allow the possibility of a continuity of treatment for an undetermined period of time.


Oral estradiol is available in the form of tablets that have to be taken daily. It’s available in the pharmacy under the brand name of Estrace or its generic form, but it can also be compounded, meaning formulated for the particular patient by a pharmacist. It’s efficient and measurable in blood.

It has to overcome the first pass effect. Liver first pass effect occurs when a drug absorbed from the gastrointestinal tract is metabolized by enzymes within the liver to such an extent that most of the active agent does not exit the liver and, therefore, does not reach the systemic circulation. Sometimes the gastrointestinal tract just poorly absorbs the drug.
Tablets are most commonly prescribed and conveniently taken. They used to be inexpensive, but that does not seem to be the case anymore. In addition, statistics show a poor compliance. Only one-third of patients pick up their prescription and among those who pick up their prescription, only one-third of them continue the medication after three months.

Transdermal patches and gels

There are two types of patches, the ones that have to be applied to the skin twice a week (Vivelle, Estraderm, Alora, etc.) and the once-a-week patches (Climara). Estradiol gels have to be applied daily. They can be compounded or prescribed under several brand names (Divigel, Estrogel, Elestrin, etc.). They are efficient, their effect is measurable and they bypass the liver. These products have to cross the skin barrier in order to reach the bloodstream. The patches can occasionally cause a skin allergy or a rash.

Vaginal applications

These are available in the form of cream (Estrace or compounded cream), tablets or rings. The cream has to be inserted with a special applicator. The oral tablets of estradiol can be inserted vaginally and be efficiently absorbed. The vaginal rings (Estring) are to remain in place for 90 days. The vaginal approach is efficient, measurable and predictable but not convenient. The ring can cause erosion and/or infection. Vaginal estrogens affect mainly the vaginal tissues and may not be sufficient to reduce menopausal symptoms.

Intramuscular injectables

Estradiol cypionate and valerate are described as long-acting estrogens in sterile oil solutions for intramuscular use. They may require a monthly office visit. They are efficient in the sense that patients feel their effect very quickly, but there is a sort of dependence with a progressive decrease in response after repetitive administration. The blood estradiol levels are very high for a few days then they fall drastically, causing significant fluctuations. The patients are never satisfied with monthly injections because of lack of stable response. In our opinion it’s the least desirable method of treatment for the long term.

3. What are the advantages of hormone pellets?

Hormone pellet implants are compacted crystals of pure estradiol injected deep in the adipose tissue of the buttocks or the abdomen. They provide consistent physiologic levels with minimal fluctuations. Their use bypasses the liver metabolism and does not increase the risk of blood clots. They are safe, efficient, convenient and well tolerated. Studies have found them to be superior to other forms of HRT regarding protection of bone density and cardiovascular health.

Hormone replacement therapy by hormone pellet implantation has been used with great success in the U.S., Europe and Australia since 1938 and found to be superior to other methods of hormone delivery. It is not experimental. The hormone pellets are compounded and packaged by specialized pharmacists under sterile conditions. The manufacturers follow strict U.S. Pharmacopeia and Food and Drug Administration regulations. The hormone pellet injectors are sterilized, and the injections performed need only minimal local anesthesia.

The complex preparation and organization for hormone pellet implantation have made most gynecologists reluctant to use this method of treatment. Another deterrent factor is the unsubstantiated bad press given to hormonal therapy in general that makes young physicians shy in implementing efficient and long-term hormonal treatments.

In our practice, after discussing pros and cons, we almost always start hormonal therapy using the more conventional gels, patches or oral methods. We offer pellets if other treatments do not provide satisfactory results. About 60 percent of patients who embark on long-term hormonal therapy end up requesting hormone pellets after comparing results and benefits.

4. Is it necessary to take progesterone?

Progesterone is the hormone of pregnancy. Its name is derived from the words “pro” and “gestation.” It’s the hormone needed for the nesting process. Menopausal women do not ovulate therefore they do not produce any progesterone naturally. There is absolutely no reason to check the level of progesterone in blood or in saliva because it’s obvious that a menopausal woman does not have any progesterone. It does not make any sense to test for low progesterone.

It is not necessary for a patient who has had a hysterectomy to take progesterone however, if a menopausal patient has a uterus, it is necessary to administer one of the three types of progesterone for several days each month. This is done to prevent an over-development of cells in the uterine lining and produce a pseudo-period in order to renew the lining.

Pure progesterone can be compounded in the form of oral tablets, cream, vaginal suppository or injectables. It’s also commercialized in the form of a capsule under the name of Prometrium. The synthetic types of progesterone available are medroxyprogesterone (Provera) and norethindrone (Aygestin or Norlutate).

5. Is it useful to take testosterone with estrogens?

Yes it is!

There are three types of androgens or “male hormones:” testosterone, androstenedione and DHEA (dehydroepiandrosterone). DHEA is produced by the male and female adrenal glands and it is sold over the counter as an anti-aging supplement. Testosterone is the main male hormone produced by the testicles, but it is also produced, in a much lower quantity, by the ovaries.

The ovaries produce some testosterone and androstenedione. Testosterone is the most efficient and useful of the two hormones, so it makes sense to add some testosterone to estrogen in a program of hormone replacement. Testosterone is useful for energy, sex drive and it completes the beneficial effects of estrogen for prevention of bone loss.

Testosterone can be compounded like estradiol and progesterone in the form of tablets, cream, gel, injectables and pellets to be given along with the estrogens. Testosterone patches are available on the market but because of their high dosage, they can only be given to males. The oral tablets are available, as methyl-testosterone, and they should be prescribed at a very low dosage because of a possible liver toxicity. Testosterone injections given with estrogen have to be closely monitored because of high fluctuations. They often cause excess facial or body hair.

The best ways to give testosterone with estrogen are with creams, gels or pellets because it almost totally bypasses the liver and can be used at a low and steady level with minimal incidence of excess body or facial hair. Of course, it is well known that some women who have never used hormone replacement can develop facial hair.

The addition of testosterone to estrogens is not absolutely necessary but it can be very useful. Most of our patients who are treated with gel or pellets recognize the benefits of such treatment. Levels of testosterone can, like estradiol, be easily monitored with blood samples.

Ready for menopause to meet its match?

Dr. Servy will work with patients seeking relief from menopause symptoms to find the hormone replacement therapy that suits their lifestyle and symptoms best.

See the original blog posting here: Estrogen Hormone Pellets

About the Author: Dr. Edouard Servy

Dr. Edouard Servy

Edouard Servy, MD, is the founder of Servy Fertility Institute and an expert in infertility treatment, including in vitro fertilization (IVF), hysteroscopic and laparoscopic surgery. He is also trained in Internal Medicine with a focus on Endocrinology and metabolic disease. As a recipient of the highly prized Irene Bernard grant, Dr. Servy came to Augusta, Georgia, in 1969 for a research fellowship under endocrinology pioneers Dr. Robert B. Greenblatt and Dr. Virendra Mahesh. After completing his training, Dr. Servy established his private practice in Augusta. Dr. Servy’s lab was responsible for the first intrauterine insemination and the first IVF-embryo transfer at blastocyst stage in the United States, as well as the first live birth after cryopreservation at the blastocyst stage following ICSI in the world.

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