Hormone Replacement Therapy

Hormone replacement therapy (HRT) is a hotly debated topic. The history of HRT is riddled with controversy and misrepresented information.

History of HRT

When looking at scientific and medical information regarding women’s health, it became evident that most of the scientific research was focused primarily on white men. In 1993, the Woman’s Health Initiative (WHI) began a series of clinical studies initiated by the National Institute of Health to address significant health issues causing morbidity in postmenopausal women.

These studies were designed to address cardiovascular disease, cancer, and osteoporosis. The trials included three main components: hormone therapy, dietary modification, and calcium/vitamin D supplementation. 

The studies lasted 8-12 years, with participant follow-up for the main intervention phase occurring in 2005. It was one of the most extensive studies of its kind, with a budget of $625 million and involving over 160k post-menopausal women. 

Study findings suggested the potential increased risk of breast cancer and stroke with the use of estrogen-progestin hormone therapy. As a result, the study was stopped in 2002, and the government issued a black box warning on all hormone replacement therapy. 

The study has since been highly criticized for leaning heavily toward women 60+ (average age was 63), which meant healthier women with menopause symptoms were excluded from the study.

In order not to skew results, women with hot flashes were excluded from the analysis since it would be evident from vasomotor symptoms if women were given a placebo.

Essentially, a substantial population of menopausal women were excluded from the study due to having hot flashes. Keep in mind that 75% of menopausal women experience hot flashes, making them one of the most common symptoms in menopause.

Dr. Mary Clair Haver, board-certified OB/GYN and Menopausal specialist and author, states this on her website:

“While the study’s objectives were noble, subsequent media coverage, news disinformation, and medical community misinterpretation of the study’s findings planted anxieties and suspicions about hormone replacement that have persisted to this day. Fear and sensationalism triumphed over science, and, for both doctors and patients, hormone replacement therapy became a source of anxiety.”

The results of the WHI study have since been walked back. 

The North American Menopause Society (NAMS) has updated its statement of support for the safety of women using HRT, stating that “for healthy women who are younger than sixty and within ten years of menopause onset, who do not have contraindications, the benefits of treating menopause symptoms with hormone therapy outweigh the risks.”

Examples of contraindications would be “ACTIVE” liver disease, heart disease, Alzheimer’s, or dementia, and estrogen receptor-positive breast cancer risks.

NAMS has cited more than 20 medical organizations worldwide, including the American Association of Clinical Endocrinology, the American Medical Women’s Association, and the American Society for Reproductive Medicine, reviewing and endorsing the 2022 updated guidance.

What are the Risks of Hormone Replacement Therapy (HRT)?

The risks of hormone therapy vary depending on which type is used, the dosage, how long hormones are taken, how they are administered, and the age when hormone therapy begins. 

In general, women who begin hormone therapy after age 60 or who begin hormone therapy more than ten years after menopause onset face more significant risks, including an increased risk of heart disease, stroke, venous thromboembolism, and dementia.

Basically…the earlier you use HRT, the better. 

FDA Approval for Hormone Replacement Therapy (HRT)

1. Vasomotor Symptoms (includes hot flashes, night sweats, heart palpitations, and sleep disturbances)
2. Bone loss: includes weakening bones and osteoporosis
3. Premature hypoestrogenism (estrogen deficiency): as a result of menopause or premature menopause resulting from surgery such as oophorectomy (with or without hysterectomy) or radiation or chemotherapy.
4. Genitourinary symptoms: includes frequent urination, burning with urination, recurrent urinary tract infections, vaginal dryness, pain with intercourse

What Are The Benefits of HRT?

• Reduces vasomotor symptoms like hot flashes
• Reduces night sweats
• Reduces mood swings
• Improves vaginal dryness
• Reduces the decrease in bone density
• Improves Sarcopenia (decreased muscle mass)
• Improves skin and hair conditions (thinning hair, skin elasticity, and bruising)
• Reduces joint pain
• Improves Diabetes: While not government-approved to prevent the onset of type 2 diabetes, HRT in otherwise healthy women with preexisting type 2 Diabetes may improve glycemic control when used to manage menopause symptoms.
• Reduces depression
• Improves cognition

What About Estrogen Causing Cancer?

Dr. Mary Clair Haver shares this on her site about HRT and cancer:

“Reality: This is perhaps the most common myth.  The above study actually found that the patients who were on CEE alone had at least a 30% decrease in breast cancer over time.  And although the CEE + MPA arm of the study did find an increased risk of breast cancer (1 woman per 1,000 women per year over baseline), the mortality from breast cancer was not increased, and is based on an older, misinterpreted study. Also, women who were on either regimens noted above, had no increased risk of cancer in the first five years of therapy.  For healthy women who are younger than 60, or are within 10 years of her onset of menopause, the favorable effects of hormone therapy on cardiac, muscle, bone and brain health should be considered.”

Traditional Hormone Replacement Therapy (HRT)

HRT is traditionally focused on Estrogen and Progesterone. Other hormones can benefit women in menopause, but for this article, we will focus on the benefits of these two hormones. 

Progesterone

Let’s discuss progesterone and its importance to our health, especially during menopause. Progesterone teams up with estrogen to keep our menstrual cycles in check and ensure our reproductive system is ticking along nicely.

It plays a crucial role in preventing the uterine lining from growing too much by balancing out estrogen’s effects. Beyond that, progesterone has a calming influence on our mood by interacting with brain chemicals. So, when our progesterone levels are low, we might experience mood swings and anxiety or feel more irritable than usual.

This hormone is also vital in maintaining bone health, helping lower osteoporosis risk as we age. Plus, progesterone contributes to keeping our skin elastic and hydrated, which means changes in its levels can affect how our skin looks and feels.

Progesterone Helps With the Following:

• Protects the lining of the uterus
• Promotes neuroprotection of the brain
• Balances effects of estrogen in the body
• Protects bone density

What Can Decrease in Progesterone Lead To?

• Mood swings (calming effect)
• Osteoporosis
• Heart disease
• Imbalance of the effects of estrogen in the body
• Loss of bone density
• Poor sleep

Potential Risks When Taking Progesterone

• Increased risk of breast cancer (although the risk is the same as being obese, approximately 7% increase after 5+ years). This risk decreases with the use of bioidentical progesterone. 
• Potential to increase blood clots in older women in specific populations with pre-existing conditions, especially when combined with estrogen
• Some women report fluid retention or weight gain, particularly with oral.
• Some women report headaches, especially women who are prone to them
• Progesterone can potentially increase “bad” LDL cholesterol in some women
• Some women report breast tenderness 

What Are My Options for Progesterone?

There are two types of progesterone.

1. Synthetic: Shown to increase risk of breast cancer (This was the type of progesterone used in the original WHI study)
2. Bioidentical: Has not been shown to increase breast cancer risk in studies.

Estrogen: 

Now, let’s dive into estrogen’s vital role in our bodies. Estrogen is a critical player in managing our menstrual cycle. During the first half of the cycle, it gets the uterine lining ready for a possible pregnancy.

This hormone is also responsible for maintaining the thickness and elasticity of the vaginal lining, which is crucial for health and lubrication. It helps keep the uterus healthy and ensures the reproductive organs are growing and functioning well.

Regarding our bones, estrogen is a champion for maintaining density and preventing bone loss. That’s why after menopause when estrogen levels drop, many women face an increased risk of osteoporosis due to weakened bones.

Estrogen doesn’t stop there—it also plays a protective role in heart health. It helps keep cholesterol levels in check by boosting “good” HDL cholesterol and reducing “bad” LDL cholesterol, which can lower the risk of heart disease.

On top of all this, estrogen affects our mood, cognition, and emotional well-being by interacting with neurotransmitters like serotonin. So, when estrogen levels fluctuate, especially during menopause, it can lead to mood changes, irritability, or even depression.

Finally, estrogen influences where our bodies store fat, often leading to more fat around the hips and thighs.

Estrogen Helps With the Following:

• Vasomotor symptoms
• Osteoporosis
• Cardiovascular disease
• Weight gain and body recomposition changes

What Can a Decrease in Estrogen Lead to?

• Reduced Vaginal Health
• Reduced Bone density: Inhibiting cells that break down bone
• Reduced Cholesterol regulation
• Reduced Blood Vessel Health (reducing the risk of heart disease and hypertension)
• Reduced Cognitive Function (studies suggest it may protect against neurodegenerative diseases like Alzheimer’s)
• Reduced Mood Stability

Potential Risks of Taking Estrogen?

• Increased blood clots: This risk is higher in women who are older, overweight, or have other predisposing conditions
• Increased risk of stroke: Some oral forms may raise the risk of stroke, specifically in those with a history of stroke or cardiovascular disease.
• There is a slightly increased risk of breast cancer:
• There is a slightly increased risk of endometrial cancer in women taking estrogen without taking progesterone in women who still have a uterus.
• There is a slightly increased risk of ovarian cancer in prolonged estrogen-only therapy.
• Cardiovascular (Heart disease) in women who start hormone therapy many years after menopause; however, menopausal women who begin therapy closer to the onset of menopause see cardioprotective benefits.
• Increased risk of dementia in older women: Some studies suggest starting estrogen later in life (after 65) may increase the risk of cognitive decline and dementia. However, menopausal women who begin therapy closer to the onset of menopause see neuroprotective benefits.

Considerations to Minimize Risk:

• Form of estrogen: Transdermal patches or gels may have a lower risk of some side effects, such as blood clots, compared to oral estrogen
• Timing of initiation: Starting HRT closer to the onset of menopause may be associated with fewer risks, especially for cardiovascular health.
• Lowest effective dose: Using the lowest effective dose for the shortest possible duration can help reduce some risks
• Combine with progesterone: For women with an intact uterus, combining estrogen with progesterone helps lower the risk of endometrial cancer.

What Are My Options for Estrogen?

The Estrogen used in HRT is Estradiol. It’s the most bioavailable estrogen, made by the ovaries. Estradiol is the primary estrogen for women throughout life. Estradiol is available to be taken in three ways:

1. Oral (slightly higher risk of blood clots)
2. Transdermal (patch)
3. Pellets

Conclusion

Navigating the complex landscape of hormone replacement therapy (HRT) requires a nuanced understanding of both the benefits and potential risks. While past controversies and misinterpretations, such as those stemming from the Women’s Health Initiative study, have historically clouded the discussion, updated research and guidelines from organizations like the North American Menopause Society provide a clearer perspective on the safe use of HRT for many women.

For those experiencing menopausal symptoms, HRT can offer significant relief, from easing vasomotor symptoms like hot flashes to maintaining bone density and supporting cardiovascular health. However, the decision to pursue HRT should be personalized, factoring in an individual’s health profile, age, and timing post-menopause. As we advance in our understanding, ongoing research continues to refine recommendations, ensuring that women are empowered with information to make informed choices about their health and well-being.