HRT Methods

 In Blog Posts, HRT

This page discusses HRT methods, including routes of administration such as oral, transdermal patches and gels, subcutaneous implants, creams, injections, suppositories and discusses estrogen, progesterone, and testosterone.

There aren’t any perfect HRT methods, and none precisely mimics nature. Fortunately, this isn’t all bad. During a woman’s reproductive years, peaks and valleys of hormone concentration in the blood are necessary to trigger ovulation and if conception does not occur, menstruation. These swings in hormone levels can affect mood and sense of well being. For example, many women experience a sense of euphoria during pregnancy when their levels of sex hormones are very high and PMS is related to the decline in hormone levels prior to menstruation.

It is of note that some patients request the “lowest possible dose” of HRT a reflection of a perception that somehow HRT is unwise, dangerous, unnatural or all of the above. This is contradicted by the weight of medical research which suggests HRT increases longevity and enhances quality of life. Ideally, HRT should be given in a dose appropriate for each specific individual as everyone differs in their needs and capacity to absorb and metabolize hormones. Ideally, this would be in an amount sufficient to fully accomplish its beneficial effect.

The hormones replaced in menopausal women include:

Estrogen

The ovarian hormone responsible for the development and maintenance of what we refer to as secondary sexual characteristics.

Progesterone

The ovarian hormone responsible for protecting the uterine lining from being overly stimulated by estrogen. Estrogen given alone (unopposed) when the uterus is present can result in the development of abnormal changes of the endometrium (uterine lining) including cancer. The addition of adequate amounts of progesterone to a program of HRT prevents this from occurring. Progesterone is not usually given following a hysterectomy as there is no uterine lining present to protect. Unfortunately, although necessary progesterone causes “PMS” like symptoms in approximately 30-40% of patients. This is mild in the majority of patients but can be severe in a small percentage.

Testosterone

The ovarian hormone responsible for sex drive, energy, muscle mass and assertiveness. Thought by many to be exclusively a male hormone it has important functions in women. Along with the other ovarian hormones, it is markedly diminished following ovarian removal or injury and consideration should be given to appropriate replacement.

Any of these sex hormones, estrogen, testosterone, and progesterone can be administered alone or in combination.

In addition, there are a number of routes of administration available to get these hormones into your system. They include:

  • Oral
  • Transdermal Patch
  • Transdermal Gel
  • Sublingual
  • Injections
  • Creams
  • Suppositories
  • Subcutaneous implants

There is no “best” HRT method for everybody and your choice may be influenced by:

  • Type of menopause
  • Concurrent medical conditions
  • Age at menopause
  • Response to previous therapy
  • Current age
  • Intolerance to previous HRT methods
  • Symptoms
  • Individual perception of HRT methods
  • Hormones to be replaced
  • Individual psychological makeup

Ultimately, the choice of which hormone or hormones and which route of administration should depend on what each individual is comfortable within view of what she perceives to be her needs, goals, and lifestyle.

Estrogen, progesterone, and testosterone can all be given using any of the described methods. But, for the sake of clarity and simplicity and to lessen confusion (mine, because I can’t figure out how to do it all at once) I will first discuss the routes of administration using estrogen alone. I will then go on to progesterone, testosterone, combination therapy, indications for each and rationales.

Estrogen Therapy

The oral route of HRT, usually a tablet taken daily is the most frequently utilized method of HRT in the world. The most well known oral estrogen replacement product is sold under the brand name Premarin and is a “conjugated equine estrogen” and is extracted from pregnant mare’s urine. There are several other oral estrogen products available and each manufacturer gives various reasons why their product is superior. I prefer to use brand name over generic products when possible because I believe some generic formulations of estrogen are not bioequivelent. The advantages of the oral route include that for most people it’s easy to take a pill, it’s relatively inexpensive and for most women, it effectively delivers estrogen into the bloodstream. There are some disadvantages. It is not effective for everyone and causes nausea or other gastrointestinal upsets and occasionally headaches. Infrequently it may cause an elevation in blood pressure. Some of these problems may be related to what is termed the bolus effect on the liver. After an estrogen tablet is absorbed by the upper gastrointestinal tract it is transported directly to the liver. This supraphysiologic amount of estrogen arriving all at once induces the cells of the liver to alter its production of enzymes.

Transdermal Patch

This method for estrogen administration has the hypothetical advantage of avoiding this “first liver pass” and at times can be effective in patients who don’t respond to tablets. There are a number of patches available today and they share some common elements. Estradiol the bioactive estrogen, a delivery system which allows the hormone to be gradually absorbed by the skin and an adhesive to keep it on. It is applied to the skin and replaced once or twice weekly as contrasted to the daily estrogen tablet. The estrogen is absorbed gradually over the length of time each individual patch is worn and this is more physiologic. It has the disadvantage of causing skin irritation in 10-30% of those who try it. Sometimes this is mild and can be alleviated simply by moving the patch to a different area of skin daily but can be severe enough to require its discontinuance. It is not as acceptable to some women who exercise strenuously or live in warmer climates as there is greater difficulty with adherence to the skin with increased perspiration. When skin irritation is the caused by the adhesive in the patch delivery system estrogen gel is available from a number of pharmacies and can be rubbed directly on the skin daily without the use of the patch system and is an effective alternative.

Transdermal Gel

A very useful method of estrogen replacement. A measured amount of gel is rubbed on the skin once daily. It is absorbed and, in theory, at least, the skin acting as a reservoir releases it gradually into the bloodstream. It is simple, well tolerated, relatively inexpensive, there is no “bolus” effect and it avoids the “first liver pass.” It is basically the patch minus the adhesive and “delivery system.” Pretty nifty, eh! And of course is not widely available in this country.

Sublingual Administration of Estrogen

In this method, a tablet, usually “estradiol”—the bioactive form of estrogen—is placed under the tongue. It is absorbed through the lining of the mouth into the blood vessels located under the tongue and then into the bloodstream. It avoids the “first liver pass” but is delivered into the blood all at one time as opposed to the gradual “trickle” delivery of the patch.

Intramuscular Injection

A common method of estrogen replacement used by many physicians. The hormone is usually mixed with a substance to slow its release into the bloodstream and depending on the dose and patient response is usually given at 2-4 week intervals. It has the disadvantage of relatively high levels soon after administration which decline rapidly after a week or so. Unfortunately, this may perpetuate menopausal symptoms which are often associated with declining rather than absolute hormone levels.

Creams

Vaginal dryness and loss of elasticity of the “vaginal barrel” can be a distressing symptom of hormone deficiency. Estrogen cream was considered a ” local” nonsystemic therapy and was an effective treatment for this problem. Years ago (and I’m sure today) it was prescribed in those instances when the doctor (presumably not knowledgeable about HRT) or the patient or both were not comfortable using other methods. The rationale being that since it was local therapy it wouldn’t pose any of the “dreaded risks” of systemic HRT. Incredibly, most doctors and patients were not aware that the vaginal absorption of estrogen is much more efficient and in the doses prescribed results in significantly higher blood levels of hormones than the oral or transdermal route of administration. Wait! It gets better! Some women found it convenient to regularly use the cream as a lubricant to facilitate intercourse. After all, they put in at night anyway. Well folks, the skin of the penis absorbs estrogen pretty well too. Not as efficiently as the vagina, but well enough to result in feminizing changes and impotence in the partners of these women.

Suppositories

These perform the same function as the cream delivery method. They are preferred by some users who find them less messy.

Subcutaneous Implantation of Estrogen Pellets

A method used primarily by physicians who special interest or training in the treatment of menopausal women. It is an effective treatment for menopausal symptoms which have been unresponsive to other therapies. I have found it to be the therapy of choice when other methods of HRT have failed as is too often the case following hysterectomy and ovarian removal. It can restore quality of life when the problem is diminished interest in sex, insomnia or persistent hot flashes. The pellets which consist of estradiol, are derived from soy—a naturally occurring substance. They are inserted into the subcutaneous tissue of the abdomen or buttock usually at 3-6 month intervals.

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