Hormonal Symphony No. 1 – Menopause – Part 1: HRT

Menopausal issues…while some women sail through this stage with no problems, many suffer multitude of symptoms. Hot flashes and mood swings, depression, vaginal dryness, painful intercourse, dry skin, night sweats, sleeplessness and irritable bladder symptoms, brain fog, memory laps….the list goes on.

According to a joint statement by The North American Menopause Society, the American Society for Reproductive Medicine, and The Endocrine Society, hormone replacement is the most effective treatment for relieving menopausal symptoms.

Here are some points to consider when you are thinking about HRT so you can have an informed discussion with your health care provider.  

1.Make sure you understand the pros and cons and understand the research papers. Many researches have demonstrated the benefits and risks HRT may cause.[1] 

Because hormones are so complex, prescribing for Hormone Replacement Therapy (HRT) requires much thought.  If someone tells you that you should take or not take estrogen after a 5-minute discussion, get a second opinion.

Benefits of HRT doesn’t stop at reduced menopausal symptoms.  Other benefits of hormone replacement therapy for post-menopausal women, include:

  • Increased elasticity of the blood vessels, allowing them to dilate (widen) and let the blood flow more freely throughout the body
  • Decreased risk of osteoporosis
  • Decreased incidence of colon cancer
  • Possible decreased incidence of Alzheimer’s disease
  • Possible improvement of glucose levels
  • Possible reduction in risk of cardiovascular disease

Risks of HRT include:

  • For women with an intact uterus, Increased risk of endometrial cancer (But only when estrogen is taken without progestin). For women who have had a hysterectomy (removal of the uterus), this is not a problem.
  • Increased risk of breast cancer with long-term use
  • Increase in inflammatory markers (such as C-reactive protein)
  • Increased risk of blood clots and stroke, especially during the first year of use in susceptible women
  • Increased risk of cardiovascular disease (including heart attack)

So all that came from numerous research data…. but wait! How does estrogen protect the heart, yet at the same time increase the risk of cardiovascular disease at the same time? This is where we need to read research carefully and understand what happened.

Most of the studies that demonstrated cardiovascular benefits were conducts as observational studies prior to 2000. Observational studies were viewed as inferior to randomized, controlled trials (RCTs) as earlier observational studies tended to inflate positive treatment effects. However, understanding this flaw, researchers improved on methodology used for this type of studies. Later, it was found that observational studies conducted between 1985 to 1998 were methodologically improved, and the effects of treatment in observational studies vs. RCTs were similar in most areas. (Benson K 2000:342:18)   RCTs also have their own biases, depending on the subjects. The Women’s Health Initiative (WHI), was the first study to come out against past evidence, and stated that women on HRT, not those on estrogen alone, had a slightly increased relative risk of heart events[2]. This only applies to women in the first year of taking HRT. Later, this data was re-analyzed, and reported that the increase in cardiac risk was seen only among women who were 20 or more years beyond menopause at the time they joined the study.[3]  And in 2007, the original author and investigators revised their report. The conclusion now indicates that women who started HRT within 10 years of the onset of menopause had reduced their risk of coronary artery disease, while those who started after that slightly increased their risk.[4] This was confirmed by an observational study, the Nurses’ Health Study.[5]  So what happened to WHI study? Well, the sample subjects were reported as healthy. But looking into the details, the median age of the women was 63. Only 10 percent of the study subjects were between age 50-54, 70% were between ages 60-79. And we know that as we age, women are more susceptible to heart diseases. Further, fully 70 percent of the study participants were seriously overweight, and half were obese. Nearly 50% were smokers or ex-smokers, and 35 percent had been treated for high blood pressure. Hardly a “healthy” population?  Yet, we rushed into making a judgement call against hormone use.

Some practitioners can be very biased about HRT one way or another. Speak with someone who is well versed on this topic and able to help you weigh out the pros and cons.

2.  HRT should be a very personalized process. No two women are alike. Before starting HRT, it’s always a good idea to have baseline hormone levels measured. This can be done via serum, saliva, or urine tests. Each test has its own utility.

Aside from hormone levels, your health care practitioner should also understand how estrogen is metabolized in your body. For example, estrogen take on one of many  metabolic pathways to become active or inactive metabolites. These metabolites affect the body differently. Some good, some not so good. Having this information will help to determine if you should be on estrogen in the first place, and what can be done to support the more beneficial route of metabolism. 

Our hormonal symphony is not just about estrogen and progesterone. You will also want to know about other hormones too. One of them is your four-point cortisol relating to your stress level. Sometimes with high cortisol demand due to chronic stress, we experience what’s known as Cortisol Steal. This is where other hormones are shunted to make more cortisol rather than sex hormones. 

3. Understanding the differences between Bio-identical hormones vs. Synthetic hormones. 

Both are derived from a laboratory. Bio-Identical means the hormone was made to have the same chemical structure as your natural hormones.  A synthetic hormone is not the same in chemical structure as that produced by your own body.  Both bio-identical hormones and synthetics are available commercially. However, bio-identical hormones can also be made at your compounding pharmacy. The benefit of compounded formulation is that you can have the hormones suitable for you at the exact dosing as prescribed. For example, if the physician prescribes a combination of two types of estrogen, Estradiol and Estriol (known as Bi-est) at 50:50 for 2.5mg daily. You will not find this in a commercial formulation, it must be compounded.  However, you must find a good compounding pharmacy that is PCCA certified for quality assurance. 

Majority of the studies conducted in the past demonstrating benefits (and harm in some) of HRT were based on women using synthetic hormones. Namely Premarin for estrogen (Conjugated Estrogen from mare’s urine), either alone, or with Provera, medroxyprogesterone acetate (MPA). 

Many are now questioning the wisdom of using synthetic hormones. We don’t really know what direct effects these synthetics have in our bodies. Hormones have specific receptor sites, and for most hormones we have receptor sites throughout our bodies. Synthetic hormones will attach to some receptor sites, but not all (e.g. MPA was designed for endometrium only). This produces incomplete messages to the body, and potential side effects. Compared to bio-identical hormones for which the body fully recognizes the molecule and is able to utilize it, I would probably opt for bio-identicals for now.

4.  Understanding Other Hormones Involved

The steroidogenic pathway is fascinating to me. Have a look at the graph! Did you know all our sex hormones originate from cholesterol?

Aside from estrogen and progesterone, some people believe taking a hormone from higher up the pathway may be better. For example, pregnenolone or DHEA.  This may seem like a good idea at first because wouldn’t these hormones simply metabolize into the appropriate hormone that your body requires?  Unfortunately, there is no guarantee they will convert into the appropriate hormones as required. First, each enzymatic step must be fully functioning. Second, as in my case, stress causes these hormones to be converted to cortisol. Symptoms of high cortisol are surprisingly like menopause: low energy, night sweats, irritability, and brain fog. Now it’s adding to the very symptoms you are trying to treat!

5. Monitor, Monitor, Monitor

So now you are on HRT. Does that mean you just keep on using it and not worry about it, ever?  Like any drugs, you must pay attention to how you are feeling, and how your body is responding to this new addition. Have your hormone levels checked regularly as our bodies change over time, and biochemistry can change due to external factors.

If you are thinking about ways to address menopausal symptoms, make sure you discuss this with your health care professional and have all your questions answered. Menopause is a serious health matter, be wise!

This is a huge topic, so I will break this into two parts. We will talk about non-hormonal support in Part 2!


[1] Cleveland Clinic Article: Estrogen and Hormones

https://my.clevelandclinic.org/health/articles/16979-estrogen–hormones

[2] Roussouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Womenès Health Initiative Randomized Controlled Trial. JAMA. 2002;288:321-33.

[3] Speroff L. A clinicianès review of the WHI-related literature. Int J Fertil. 2004; 49:252-67.

[4] Rossouw JE, Prentice RI, Manson JE, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA. 2007; 297:1465-77.

[5] Grodstein F, Manson JE, Stampfer MJ. Hormone therapy and coronary heart disease: the role of time since menopause and age at hormone initiation. J Women’s Health. 2006;15:35-44.

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