7 Oct 2024

HRT: Expert Insights with Dr. Isabelle Martineau (Part 1)

In this Q&A, Dr. Isabelle Martineau, a leading endocrinologist and functional medicine expert, answers key questions about Hormone Replacement Therapy (HRT) during perimenopause and menopause. Her expertise sheds light on how HRT can benefit women’s health during this crucial life stage.

1. Can you explain the potential benefits of HRT for women in perimenopause and menopause?

Menopause typically occurs around age 51, defined as having no periods for one year. If it happens between ages 40 and 45, it’s called early menopause; before 40, it’s premature menopause. The timing affects our approach to hormone choices.

For women experiencing premature or early menopause, supporting them with bioidentical hormones for several years is important. The benefits of bioidentical hormones are significant. They help alleviate symptoms like hot flushes, night sweats, insomnia, irritability, mood swings, and brain fog. These symptoms can be quite debilitating. It’s essential to understand that, at 50, many women are at the peak of their careers, with significant responsibilities, managing teams, and making important decisions. Suddenly, they can feel like they are not functioning properly, and we cannot let this happen.

So, when there are no contraindications, we begin to substitute the hormones that the body is no longer producing. When a woman has not had a period for a year, it means her ovaries are no longer producing oestrogens or progesterone.

During perimenopause, which precedes menopause, cycles become shorter and shorter due to a decline in ovulation quality. As the corpus luteum (the structure that secretes progesterone) becomes less effective, progesterone production decreases, resulting in shorter cycles. Eventually, oestrogen levels also start to decline. It is like a rollercoaster for oestrogen levels, fluctuating up and down, while the progesterone decline is steadier. Eventually, cycles become longer and longer until they stop altogether. While this is a general pattern, not every woman experiences it in the same way. Typically, by the age of 45, cycles may shorten from 28 days to 26, 24, or even 21 days, as progesterone secretion diminishes.

What are the implications of the loss of these hormones?

  • Bone Health: Hormone replacement is crucial for bone protection. The process of bone turnover, which involves bone construction and destruction, is significantly affected by the loss of oestrogen and progesterone. Without these hormones, bone loss accelerates, leading to osteopenia and, eventually, osteoporosis. In advanced age, osteoporosis increases the likelihood of fractures. For example, in your 80s, a simple fall can easily result in a fracture due to fragile bones. This often leads to hospitalisation, and studies show that fractures in the elderly significantly increase the risk of death. It also reduces the chances of regaining independence if one becomes wheelchair-bound after a fall.
  • Brain Protection: Oestradiol and progesterone receptors are abundant in the brain. We see this clearly in cases of postpartum depression, which can occur due to a sudden drop in oestradiol and progesterone after childbirth. Although the decline in hormones is slower at menopause, it can still lead to depression and anxiety, particularly due to progesterone loss. Progesterone metabolites in the brain increase the expression of GABA, an important neurotransmitter for relaxation and sleep. This is why women who don’t supplement may experience insomnia, which can range from mild to severe, often exacerbated by night sweats. Poor sleep can lead to concentration issues, memory problems, and brain fog, all of which can be challenging for women managing demanding work responsibilities. Studies have also shown that women on bioidentical hormone replacement therapy (BHRT) have a significantly lower risk of developing dementia and Alzheimer’s disease. While other factors, such as exercise, also play a role, oestradiol and progesterone have a profound impact on brain health.
  • Cardiovascular Protection: Today, the leading cause of death in women is cardiovascular disease, which surpasses breast cancer. Before menopause, women have a much lower incidence of cardiovascular disease than men, due to the protective effects of oestradiol and progesterone. Once these hormones decline, a woman’s cardiovascular risk equals that of a man. By supplementing with oestradiol and progesterone, we can reduce cardiovascular disease risk by improving insulin resistance, lowering apolipoprotein levels, and positively impacting the lipid profile—thus reducing the risk of strokes and deep vein thrombosis (DVT).
  • Quality of Life: Vaginal dryness, often alleviated by HRT, can affect sex life and relationships. Moreover, HRT reduces the risk of bladder infections, as natural oestradiol and progesterone protect the mucosa of the bladder and vagina. Postmenopausal women tend to have more urinary infections because their mucosa is not as well-protected as before. Skin and hair also benefit from continuing with bioidentical oestradiol and progesterone.
  • Weight Gain: Many women gain weight around menopause, especially visceral fat, which can be a major concern. Even with changes to diet and lifestyle, some women struggle to lose weight. This difficulty is partly due to increased insulin resistance, which can be improved with oestradiol.

It is essential to address both the immediate symptoms of hormone decline and the long-term benefits for the bones, brain and heart.

At 50, many women are at the peak of their careers… Suddenly, they can feel like they are not functioning properly, and we cannot let this happen.

2. If I decide to try HRT, what should I take?

What hormones are available to doctors, and which ones do I prefer to prescribe? There is a range of different hormones and formulations. The types of hormones fall into two main categories:

  • Those produced by the pharmaceutical industry.
  • Those produced by compounded pharmacies.

The pharmaceutical industry can provide bioidentical hormones, available on the market through regular pharmacies, including the NHS. This is important to note. We also have progestins, which are synthetic forms of progesterone. Progestins are created by modifying the progesterone molecule slightly, which gives them different properties. Oestradiol, a key hormone for menopause, can be produced either in the pharmaceutical industry or by compounded pharmacies and is bioidentical. When you examine it under a microscope, it’s the same molecule that a woman naturally produces.

Formulations of Oestradiol:

In terms of formulations, there are several ways to absorb oestradiol:

  • Creams or patches applied to the skin.
  • Oral formulations, such as capsules or lozenges.
  • Vaginal pessaries.

Progesterone is mostly available as a capsule, either from the pharmaceutical industry or compounded pharmacies.

Choosing Between Options for Oestradiol

How do we choose between the options, particularly for oestradiol? Should we opt for the skin-based (percutaneous) route like creams and patches, or go with a lozenge or capsule? Many studies since 2000 have shown that using creams or patches can lower the risk of breast cancer. Personally, I haven’t seen any studies suggesting that the lozenge (which bypasses the liver) has the same breast cancer risk reduction as the patch or cream. This is a common concern for women due to a study published in 2001 (likely referring to the Women’s Health Initiative study in the USA).

Absorption and Hormone Levels

It’s important to understand that when oestradiol is given through the skin, the hormone levels that reach the body’s systems are often lower than with oral forms. While the percutaneous route avoids the liver the first time it’s absorbed, eventually, all hormones pass through the liver to be detoxified and eliminated via the gut, just like with oral formulations. What’s key here is not just the liver bypass but how well the liver detoxifies hormones.

Breast cancer existed long before HRT, and one risk factor is the liver’s ability to detoxify hormones.

The Role of the Liver in Hormone Detoxification

Breast cancer existed long before HRT, and one risk factor is the liver’s ability to detoxify hormones. A key enzyme in this process is COMT. Depending on the genes inherited from your parents, your enzyme could be fully functional, partially functional, or working at only 25% or less. Women with lower enzyme activity are less able to detoxify hormones. In functional medicine, we use urine tests to evaluate how well someone is detoxifying hormones and can also conduct genetic tests.

Gut Microbiome and Detoxification

Another crucial factor in detoxification is the gut microbiome. If the microbiome isn’t healthy—for example, if certain bacteria secrete too much beta-glucuronidase, an enzyme that recycles hormones like oestradiol—it can disrupt hormone detoxification. This can be more significant than whether the hormones are absorbed through the skin or orally. Analysing the microbiome helps us understand if these bacteria are present in high levels, and we can modify a woman’s diet to lower them. Similarly, with the liver, while you can’t change your genes, you can adjust your diet to support better hormone detoxification, for instance, by increasing foods that promote liver function. I often recommend a supplement called DIM (an extract of broccoli) to aid in oestradiol detoxification. It’s crucial to explain these mechanisms to women, even when they are on bioidentical HRT.

Post-Menopausal Hormone Use

When it comes to formulations, some women have been post-menopausal for 5-10 years and may benefit from reintroducing hormones. For these women, I tend to favour percutaneous options (creams or patches), as they deliver lower concentrations of hormones. Most women don’t want to restart their periods after years of being menopausal. For women in their early 50s who are still cycling, they often don’t want to experience periods again either. To manage this, I prescribe lower doses of oestradiol and progesterone, often via a cream or patch.

When Patches May Not Be Suitable

However, there are cases where patches may not be suitable. Women who have experienced severe PMS, mood swings, or depression may find that patches trigger these symptoms again because of the fluctuations in hormone release. In those cases, an oral formulation might be better.

Tailoring Hormone Formulation Choices

Ultimately, choosing the right hormone formulation requires understanding a woman’s hormonal history and current symptoms. We tailor the approach and dosage accordingly.

 

Part 2 is now available! Dive deeper into our conversation with Dr. Isabelle Martineau, as we continue exploring invaluable insights into managing perimenopause and menopause through Hormone Replacement Therapy (HRT). You can visit Dr. Martineau’s website at Medical Art Practice

 

READ PART 2 NOW