What You Need to Know About Hormone Replacement Therapy

(Part 1, General Considerations)

The complex changes which take place during menopause often involve multiple of the body’s most important hormones. Corrective therapy, referred to as Hormone Replacement Therapy (HRT), requires diligence and perseverance from both doctor and patient so that the treatment is both safe and effective. It is now a misnomer that there is only one hormone that becomes deficient with menopause. Indeed, one of the most important recent advances in HRT strategies is that any of the following hormones can become deficient during the time of menopause:

  • Estrogen
  • Progesterone
  • Testosterone
  • DHEA,
  • Growth Hormone
  • Melatonin
  • Thyroid Hormone
  • Cortisol

Potential benefits and side effects of HRT can ultimately depend upon several factors. As with any medical condition and its appropriate treatment, a patient who is fully engaged and cooperative with a provider who openly discusses the range of treatment options will often lead to the most favorable outcome. In addition to the specific hormone used as part of a treatment strategy for menopause relief, the potential benefits and side effects of HRT will depend on these considerations:

  • Physiological dose vs supraphysiological dose
  • Hormone type or brand
  • Route of administration for hormone
  • Comprehensive HRT vs mono-HRT
  • Regularity of follow-up visits

Physiological dose vs Supraphysiological dose

Physiological doses are doses that mirror the body’s normal daily output of any particular hormone. World famous expert HRT physician Thierry Hertoghe, MD, states that physiological doses are those, “which fall in a range between a fraction of the normal daily production in the body up to the maximal daily secretion in healthy adults.” Supraphysiological doses (also called pharmacological doses), on the other hand, are doses which exceed the maximal daily secretion in healthy adults. This distinction is important because side effects are far less likely to occur when HRT is prescribed at physiological doses. An obvious example of this is when a woman takes birth control pills for contraception. The dose of birth control pills is typically designed to be supraphysiological specifically to control ovulation and menstruation. Unfortunately, side effects are very common amongst women taking birth control pills.

Hormone Type or Brand

Like any other product for sale in this country the hormones utilized in HRT must be manufactured. In most cases the hormones require a prescription so the agents are manufactured by either a commercial pharmaceutical company or a compounding pharmacy. There are two exceptions, however. Neither melatonin nor DHEA require a prescription in this country. Though these two hormones are sometimes also made by compounding pharmacies, more often they are manufactured by what are called nutraceutical companies.

The terminology describing the types of HRT hormones can be confusing. Words like, “natural”, and “synthetic” can be great for marketing purposes though offer little clarity for most patients. In truth, all of the hormones used in HRT are synthesized in a lab somewhere so that particular term does not hold much value. The word “natural” tends to have so much ambiguity in medicine and wellness it too has little use. The most important and descriptive terms to use when referring to HRT hormones are “bioidentical” and “non-bioidentical”. Non-bioidentical hormones are sometimes also referred to as “modified”.

Bioidentical hormones synthesized in a lab or pharmacy are exactly the same hormones produced by the human body. They are the same structure, they are metabolized by the body in the same manner, and they interact with our hormone receptors in ways identical to that of our own hormones. Bioidentical hormones are manufactured by both large commercial pharmaceutical companies and smaller compounding pharmacies. By law, the bioidentical hormones themselves cannot be patented. However, special preparations of the bioidentical hormones such as creams, gels, or lozenges can be patented.

Non-bioidentical hormones do not naturally occur in the human body. They would not exist in nature unless a laboratory or pharmacy made them. They typically have the same base structure as bioidentical hormones, though their structure has been modified in some way. They do not fit and influence receptors in the body in the same manner as bioidentical hormones. They are metabolized differently by the body. They are designed this way typically to have a stronger or more lasting effect than bioidentical hormones. Non-bioidentical hormones are always patented. A recent review of scientific literature comparing the clinical use of bioidentical hormones to non-bio-identical honromes revealed that bioidentical hormones are associated with lower risks and better efficacy than there non-bioidentical counterparts. 1

Route of Administration for Hormone

Hormones can be administered by many different routes and the particular route chosen by the prescriber and patient can significantly affect how hormones benefit the body or cause potential side effects. The main routes of administration for hormones are described in the following table.

Hormone Administration Route Table
Route of Intake How Hormone is Taken Where it is Absorbed in Body
Oral Placed in mouth and swallowed Absorbed in intestines; passes through liver prior to reaching bloodstream where it can be inactivated or may accumulate
Sublingual Placed under tongue and allowed to melt Approximately half absorbed directly into bloodstream through mucous membranes of mouth. Remainder absorbed as oral intake is absorbed
Buccal Placed between cheek and gums and allowed to melt Approximately half absorbed directly into bloodstream through mucous membranes of mouth. Remainder absorbed as oral intake is absorbed
Nasal Sprayed into nose Absorbed through mucous membranes of nose into bloodstream
Transdermal Applied as gel or cream onto skin Slowly penetrates through skin and absorbed directly into bloodstream
Subcutaneous Injected under the skin Slowly absorbed into bloodstream from fatty tissue under skin
Intramuscular Injected into muscles Slowly absorbed into bloodstream from muscle tissue
Intravenous Injected into veins Absorbed directly into bloodstream
Vaginal Creams ovules or capsules into the vagina Absorbed through vaginal mucous membranes

Another important consideration concerning the route of administration is when the hormone is taken. Most hormones have a very specific rhythmic cycle during the day in which they are produced by the body. Blood levels of hormones experience peaks and valleys throughout the day. Most practitioners attempt to mimic the body’s natural output by dosing patients near times the hormones are produced by the body. Dosing at suboptimal times can sometimes lead to less effective treatment outcomes or unwanted side effects. In fact, a recent study looking at the cyclical output of hormones showed that disruption of the normal cycle can significantly increase risk factors for several types of inflammatory diseases. 2

Comprehensive HRT vs Mono-HRT

Hormones are designed to be in balance with one another. A great analogy is a musical orchestra. All instruments must be in tune and balanced with one another or else the entire orchestra sounds very disconcerting. Similarly, when one or more hormones become s out of balance with the other hormones the body does not function very well. The ultimate goal of HRT is to create a good balance among all hormones. Many hormones stimulate or slow down the effects of other hormones. For example, thyroid and growth hormone replacement therapies are often not well tolerated if a person has a cortisol deficiency. Another example is that estrogen is not tolerated and may be unsafe without administering progesterone in conjunction. There are many more examples of corrective hormone therapies that are not well tolerated.

Regularity of Follow-up Visits

Treating hormone deficiencies with HRT is a delicate and challenging wellness endeavor. It is very common for initial dosages of prescribed hormones to be not optimal and adjustments to dosages are frequent during the course of treatment. Among the expectations of HRT are that the patient feels well, sees improvement in symptoms, experiences no side effects, and has long term benefit from taking the hormones. Communication between patient and doctor becomes very important so that all relevant information is known. Experts in HRT also understand that the body’s ability to produce and balance hormone levels is greatly impacted by things like diet, environment, lifestyle, exercise, sleep, and stress. Guidance on these important influences is also part of regular follow-up visits.

Part 2 in the series, “What You Need to Know About Hormone Replacement Therapy”, will be an in depth discussion on two of the most commonly prescribed hormones in HRT for menopause: estrogen and progesterone.


  1. Holtorf, K. Postgrad Med. 2009 Jan;121(1):73-85.
  2. Mate, I. Curr Pharm Des. 2014 Jan 30.

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