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The Ups & Downs of Bioidentical Hormones: Everything You Should Know



You may have heard hormone replacement therapy is harmful, yet your doctor says it is safe. You get a second opinion from a naturopath who tells you the only safe hormones are bioidentical hormones made from yams, and she will write you a prescription for a special cream sent to a compounding pharmacy that your insurance doesn't cover. Now you don't know who to believe--was your doctor misinformed?


Your mom told you tell you horror stories of "hormones” causing cancer and strokes yet your best friend tells you hormones brought saved her marriage and her sanity.


You look it up on Google and the information is conflicting.


Hormones are The Fountain of Youth!


Hormones cause breast cancer and strokes!


You don’t know what to believe.


This is part one of a series on perimenopause and menopause that helps you sift through the good, the bad, and the ugly so you can make an informed decision.


At Hearthside Medicine, we want you to be aware of the risks and benefits of all treatments and empower you to make an informed decision. While we lean towards bioidentical hormones over synthetic hormones, it's important to note that hormones are not safe for everyone.


"Bioidentical hormones" (bHRT) certainly has become a BUZZword in the natural health industry and in women's health circles. They are often touted as being "safe and all natural" and "derived from plants."


The North American Menopause Society (NAMS) reports that about 1.4 million women are using bioidentical hormones (bHRT) and that 40% of all prescriptions for menopausal hormone therapy are for bHRT.


Here are some common questions we field at Hearthside Medicine:


Why might I benefit from hormones?

Do hormones cause breast cancer and strokes?

Is bioidentical really all natural?

Can I just use those over the counter menopause supplements?

Are hormones regulated by the FDA to ensure they contain what they say they contain and meet safety standards?

Is one route safer than other routes?

Who should NOT take them?

What side effects do I need to be aware of?

When can I or should I start them and for how long?

What is the difference between a compounded hormone and what I can get at a regular pharmacy?

What can I try instead of hormones for my perimenopause symptoms?


At Hearthside Medicine, we are all about supporting our patients with the safest and most natural options available, so let's run through these questions together!


First, why consider hormones?


Most people start to weigh their options and explore the idea of hormones when they start to experience symptoms of perimenopause or when they undergo a surgery that puts them into immediate menopause (induced menopause/surgical menopause). Others will look first for holistic options and supplements to treat their symptoms (we have an entire blog for that! Check it out: https://www.hearthsidemedicine.com/post/navigating-menopause-with-integrative-medicine


Signs of perimenopause may include some or all of the following:

  • Hot flashes

  • Night sweats

  • Insomnia (due to night hot flashes)

  • Lack of energy

  • Mental haziness

  • Mood swings

  • Depression

  • Decreased libido

  • Decreased ability to achieve orgasm

  • Vaginal dryness

  • Bone loss

  • Elevation of cholesterol, decrease in good cholesterol (HDL) and increase in bad cholesterol (LDL)

  • Deregulation of carbohydrate metabolism

  • Frequent vaginal and urinary infections

  • Weight gain

  • Hair loss

  • Skin dryness

  • Deregulation of thyroid hormone


Perimenopause can start as early as 10 years before menopause, and the average age of menopause is 51--meaning, if you are headed into your 40 or already there, the above symptoms may already be happening.



To better understand what is happening in your body from a physiologic perspective and how low hormones can impact your overall health in depth, read my blog about perimenopause & menopause https://www.hearthsidemedicine.com/post/low-sex-drive-moods-weight-insomnia-it-might-be-perimenopause-sooner-than-you-think





How can taking hormones help me?


Hormone therapy (HT) is a good way to relieve many unwanted symptoms but, as with all medical treatments, it has some risks. The safety of HT depends largely on the age of the patient and any underlying medical conditions they may have (smoking, personal or family history of breast cancer, history of blood clots, etc). Some menopause experts believe non-oral routes of estrogen are also safer as they bypass the liver and thus are associated with fewer blood clots.


For most, the risks are few and the potential benefits are many.

Hormone therapy can benefit you in many aspects of your life. It can help improve sleep, increase energy levels, increase your sex drive (libido), decrease urinary problems, make sex less painful, protect your bones, increase your good cholesterol (the kind we need to combat the bad), help maintain a healthy weight, reduce risk of colon cancer, and in some cases, alleviate depression and/or anxiety.


Some research even suggests a decline in production of hormones can increase your vulnerability to cardiovascular disease and osteoporosis.


What are the risks and benefits of HRT?


In a thorough review of past and current studies, it is painfully apparent that a general lack of consensus persists among providers regarding benefit vs risk of HRT due largely in part to the WHI study of 2002 elaborated above.


According to the North American Menopause Society (2017), contraindications for HT include unexplained vaginal bleeding, severe active liver disease, prior estrogen-sensitive breast or endometrial cancer, coronary heart disease (CHD), stroke, dementia, personal history or inherited high risk of blood clotting disease, porphyria cutanea tarda, or hypertriglyceridemia, with concern that endometriosis might reactivate, migraine headaches may worsen, or leiomyomas may grow.


More common adverse effects include nausea, bloating, weight gain, fluid retention, mood swings (progestogen-related), breakthrough bleeding, headaches, and breast tenderness.

Potential risks of HT initiated in women aged younger than 60 years or who are within 10 years of menopause onset include the possible risk of breast cancer with combined EPT, endometrial hyperplasia and cancer if estrogen is unopposed or inadequately opposed, venous thromboembolism (VTE), and biliary issues. Additional risks across ages include myocardial infarction (MI), stroke, and dementia.


For a more in depth review of safety and side effects read our blog: https://www.hearthsidemedicine.com/post/estrogen-progesterone-testosterone-side-effects-safety


Benefits of hormone replacement therapy are believed by many providers to include the following:

  • Increased elasticity of the blood vessels, allowing them to dilate (widen) and let the blood flow more freely throughout the body

  • Improved short-term symptoms of menopause such as hot flashes and mood swings, as well as vaginal dryness, dry skin, sleeplessness and irritable bladder symptoms

  • Decreased risk of osteoporosis and fractures (broken bones)

  • Decreased incidence of colon cancer

  • Possible decreased incidence of Alzheimer’s disease (data not conclusive)

  • Possible improvement of glucose levels

The health risks of HRT include:

  • Increased risk of endometrial cancer (only when estrogen is taken without progestin) For those who have had a hysterectomy (removal of the uterus), this is not a problem

  • Increased risk of breast cancer with long-term use or depending on age

  • Possible Increased risk of cardiovascular disease (including heart attack) with long-term use

  • Increase in inflammatory markers (such as C-reactive protein)

  • Increased risk of blood clots and stroke in susceptible patient (obese patients, those who smoke, those with history of clots)

All those taking hormone replacement therapy should have regular gynecological exams (including a PAP smear). The American Cancer Society also recommends that those over age 50 should:

  1. Perform breast self-examination once a month

  2. Have a breast physical examination by health care provider once a year (we are happy to do that for you as part of your annual wellness exam)

  3. Have a mammogram once a year



Heart attacks — The risk of having a heart attack related to use of hormone therapy appears to depend on your age. According to the landmark 2002 WHI study, there is no increased risk of heart attacks related to hormone therapy in women who:

●Became menopausal less than 10 years before starting hormones

or

●Were age 50 to 59 years when they took hormone therapy

Other studies since the WHI also report that hormone therapy does not increase heart attack risk in younger women; some suggest it might even lower the risk slightly. In the WHI, women who become menopausal more than 10 years ago or over age 60 years were at increased risk of having a heart attack related to hormone therapy.


Breast cancer — In the aforementioned WHI study using synthetic hormones primarily in those over 60, there was a small increased risk of breast cancer in those who took combined estrogen-progestin therapy but not in women who took estrogen alone. Those with a uterus must take progesterone with estrogen to prevent endometrial cancer. Those without a uterus can safely take estrogen alone. Again, this breast cancer data is based on the WHI study which primarily examined those older than 60 using synthetic, oral hormones. Now, we are encouraging patients to start younger, stop sooner, consider using bio-identical hormones, and consider using non-oral routes.


Osteoporotic fracture



The risk of breaking a bone at the hip or spine because of osteoporosis is lower in women who take estrogen-progestin or estrogen alone. However, currently hormone therapy is not recommended by menopause experts to prevent or treat osteoporosis, because there are bone medicines (called bisphosphonates ) that are very effective and have fewer serious risks. That being said, being on HRT will certainly help preserve bone strength. Other ways to minimize risk of osteoporosis includes weight lifting, taking calcium citrate 1200-1500 mg with magnesium and vit D, running, maintaining a healthy weight, not smoking. avoiding too many substances that leach calcium from the bones such as coffee and carbonated beverages.


Dementia — Among the older women studied in the WHI, there was no improvement in memory or thinking with either estrogen alone or with combined estrogen-progestin but there was an increase in the risk of developing dementia. No increase in dementia risk was seen in the younger menopausal women in the WHI or in other studies.

Some experts think that estrogen treatment might be helpful for preventing dementia if you take it in the earliest years after menopause (although this is not proven); taking it many years after menopause seems to be harmful.


Depression



Many women experience anxiety and/or depression during the transition to the menopause. Some studies show that estrogen treatment helps improve mood and decrease depression. However, some women need to be treated with both estrogen and an antidepressant to feel completely better.


Will HT bring my periods back?



To avoid monthly bleeding you will use estrogen and progesterone daily, continuously. Some have breakthrough bleeding (irregular spotting or bleeding) with the continuous regimen, perhaps due to differences in uterine anatomy or fluctuations in the body’s natural estrogen production. A common solution to eliminate bleeding is a progestin containing intrauterine device (IUD), such as Mirena.


Does HT cause weight gain?


Many people have weight gain at about the same time they begin HT due to changing hormone levels, so they believe that HT is the reason for weight gain. In reality, statistics show that over time, those using HT after menopause have less weight gain than those not using HT. A very will have fluid retention with HT, but this is not common. Weight gain is part of normal physiology of aging. Metabolism slows down during perimenopause, so one’s weight will increase if the same caloric intake and same level of exercise is maintained. One way to increase your metabolic rate is to add muscle-building to your exercise routine. Muscle tissue burns more calories than other tissues, even at rest. Some people experience improvement in muscle mass and reduction of subcutaneous fat when testosterone supplementation is included as part of their hormone replacement regimen.


Monitoring and Follow-up After initiation of HT


When we initiate hormone therapy for our patients, we generally require follow-up visits and lab levels be scheduled at 4-6 weeks, 3 months, 6 months, and then annually if remaining stable.

Many people require at least a follow-up visits to adjust hormone dosage before satisfaction is achieved.


After that, yearly visits are usually sufficient.


Blood tests are sometimes indicated, but not always. If testosterone or thyroid medication is given, blood levels are especially important. Some sources claim that saliva testing is a good way to monitor hormone levels, but there is no scientific data to support this practice in monitoring ovarian hormone levels. The best indicator that you are using the correct dose of estrogen and progesterone is that your symptoms are controlled and you have no side effects.


How are bioidentical hormones different than synthetic hormones? Are they safer?






First, let's define "bioidentical"--how is it different than non-bioidentical?


Bioidentical hormones are defined as man-made hormones that are very similar to the hormones produced by the human body. Common hormones that are matched are estrogen, progesterone and testosterone.


Definition of bioidentical:


This broad definition does not address the manufacturing, source, or delivery methods of the products and thus can include non–FDA-approved custom-compounded products as well as FDA-approved formulations. Bioidentical hormones may be synthesized from plant or animal sources or completely synthesized chemically. They are offered both as products approved by the Food and Drug Administration and as compounded preparations that are not FDA-approved.


Though it is often advertised that products that are made from plants like soybeans and yams are “natural” choices, they are altered greatly in a lab so are no longer natural when done with processing. They have similar risk and benefit profiles to synthetic hormones, though at here at Hearthside Medicine, we do prefer bioidentical over synthetic for all our patients using hormones, including patients using hormones for non-menopausal reasons.


The US Food and Drug Administration (FDA) has approved a number of preparations of bioidentical estradiol and progesterone, which are molecularly identical to the structure of the hormones generated by the human body. They have been through testing for safety and purity to be sure each dose has the same amount of hormones.


Compound bHRT


Some prescription forms of bioidentical hormones are pre-made by a drug company. Other forms are custom-made by a pharmacist based on a providers' prescription. This is called compounding.


The compounded forms have not been tested and approved by the FDA.


Customized bioidentical hormones are often advertised as being a safer, more effective, natural, and an individualized alternative to conventional hormone therapy. However, these claims remain unsupported by any large-scale, well designed studies. That being said, there are some benefits for patients to have their hormones compounded.


Like supplements, which are not regulated by the FDA, the lack of FDA oversight for compounded hormones has some providers wary of additional risks regarding the purity and safety of custom compounded bioidentical hormones.


Although custom hormone combinations often include blends of the same ingredients found in FDA-approved bioidentical hormones (i.e., plant-derived 17β-estradiol or micronized progesterone), some custom compounded preparations include additional hormone varieties (i.e., estriol, pregnenolone, and DHEA). These additional hormones have not undergone adequate testing and are therefore not included in any FDA-approved products.


Currently, national societies and expert recommendations state that the risks and benefits of conventional (synthetic) and bioidentical hormones should be considered equal


Bioidentical hormone therapy (BHT) is a “hot topic” in women’s health. So what is it? It means the hormones are chemically identical to those produced by the human body, and therefore, are considered more natural by some than non-identical hormones (sometimes referred to as “synthetic” hormones). However, one should not make the mistake of thinking that bioidentical comes without any potential side effects or adverse effects.


Hormones that are not bioidentical are commonly known as synthetic hormone formulations. Examples are conjugated equine estrogens (CEE)(Premarin), oral contraceptive pills, medroxyprogesterone (Provera), and methyltestosterone.


BHT are made in the laboratory and are based on compounds found in plants. Examples may include soybeans or wild yams.


Estradiol, progesterone, testosterone, and other hormones can be produced as bio-identical formulations – some are available commercially, some are not.

Through specialized compounding pharmacies, we can provide customized prescriptions of bioidentical estradiol, progesterone, and testosterone (though sadly, they are rarely covered by insurance). For example, I will often prescribe a compounded troche that contains estrogen, progesterone, and testosterone in it—this makes it easier for my patients because they get 3 in 1 rather than having to take all three forms separately.


The term bioidentical hormone does not have a standardized definition and thus often confuses patients and practitioners. Those who request bioidentical HT (BHT) from their providers may have differing expectations. Depending on the circumstances, it can mean natural (not artificial), compounded, plant derived, or chemically identical to the human hormone structure. The Endocrine Society has defined bioidentical hormones as “compounds that have exactly the same chemical and molecular structure as hormones that are produced in the human body.”


Are bioidentical hormones safer than synthetic hormones?


This answer depends on who you talk to. Overall, data shows support for bHRT being safer than synthetic. However, it is important to remember that just because it is bioidentical doesn't mean it is completely without risk or "as natural as a plant." At our practice, we prefer to prescribe bHRT over synthetic.


Clinical trials have shown that transdermal estradiol, a bio-identical product, is safer than oral estrogen, because the transdermal route avoids first-pass metabolism by the liver, thereby reducing the risk of blood clots and gallbladder disease, when compared to oral estrogen.


As for breast cancer risk, studies do not show an advantage of one type of estrogen over another. Some studies of CEE (Premarin) show no breast cancer increase and some show a small increase. The same is true for (human identical) bio-identical estradiol. Studies suggest that increased risk is observed when any estrogen is combined with a synthetic progestin, and that synthetic progestins may be the component of combined long-term HT that is most linked to breast cancer.


Meanwhile, there is no study linking bio-identical progesterone with increase in breast cancer. Data does suggest bioidentical progesterone is safer than synthetic progestin because the latter opposes estrogen’s benefits on heart health, while bioidentical progesterone does not interfere with estrogen’s cardiovascular benefit.


But I heard that hormone replacement therapy causes breast cancer and blood clots……?


In 2002, results from a large study of hormone therapy by the Women’s Health Initiative (WHI) rocked the world of patients and providers alike. This very large study found that there was an increased risk of harm in those taking hormones. If you have heard that hormones are very dangerous, it is likely because of this study. Patients and providers alike went from liberally endorsing hormones to being very conservative with them and often counseling against their use.


The WHI study revealed an increased risk of breast cancer, cardiovascular disease, stroke, and blood clots in those taking synthetic estrogen and synthetic progesterone, also known as conjugated equine estrogen (CEE) (Premarin) and medroxyprogesterone acetate (MPA) compared with those in the placebo group.


The most alarming statistic to come from the WHI was that those taking HRT had a 26% increased “relative” risk of breast cancer over those who weren’t on hormones. Media took hold of that terrifying number and ran with it, creating fear in patients and providers that has reverberated since.


Providers who are advocates of HRT are quick to point out the numerous ways in which this study was flawed and risks over-played, to the detriment of perimenopausal and menopausal individuals everywhere.


HRT provider proponents first note that relative risk and absolute risk are very different. The absolute risk of breast cancer was increased in the estrogen+progestin group by 8 breast cancer cases out of 10,000 women. That’s an absolute increase of 0.08%--not 26%.


Secondly, HRT proponents note that the study was based on synthetic hormones (Premarin and medroxyprogesterone) as opposed to bio-identical hormones. They also highlight that the study only examined oral route versus safer routes that bypass the liver, such as creams, patches, and troches. Oral hormone (pills) have to pass through the liver (called “first pass”), which is associated with increased blood clot risk than non-oral routes (with the exception of troches, which dissolve in the mouth and therefore are not subject to “first pass.”


Advocates of HRT importantly note that women recruited to complete the study were, on average, 63 years old—around 12 years past the average age of menopause, 51. That means that very few of these patients were experiencing the symptoms that HRT would be prescribed for in the first place. The researchers specifically excluded patients who had moderate to severe hot flashes.


Because these patients were significantly older than women entering menopause, they also had multiple health issues that are associated with advancing age and nearly 50% reported a history of smoking which contributes greatly to cancers of all types and blood clots.


As a result of the WHI study, many patients now ask their providers for non–FDA-approved compounded bioidentical HT (CBHT), believing that it is safer than FDA-approved therapy, despite that fact that there are not nearly as many studies regarding their safety as FDA-approved hormones.

At what age should I start HRT and at what age should I stop?

Younger patients are less likely to have adverse events like heart attacks, blood clots, and stroke.


Hormone therapy is appropriate for those in early menopause and sometimes even in perimenopause because they are likely to have quality-of-life benefits that outweigh the small likelihood of adverse events.


HRT should not be used for long-term disease prevention in any age group, because there is concern about a slight increased risk of blood clots and stroke, especially as one ages and the longer they have been on the HRT.


The bar is set very high for long-term use because of those potential risks.

Today, the FDA urges those who take hormone therapy to take the lowest helpful dose for the shortest amount of time.


Generally speaking, most providers will discourage starting HRT if one is 10 yrs beyond the start of menopause because at this point, theoretical risks starts to outweigh benefit.


What are my options for taking hormones?

For an in-depth review of your choices and options for HRT, please read our blog here: https://www.hearthsidemedicine.com/post/an-in-depth-look-at-your-hormone-options


HRT is not recommended for those who have:


It is not advised to take HRT with a personal history of breast cancer, blood clots, strokes, or heart disease. Obesity and smoking also increase the risk of negative outcomes from HRT.

  • History of prior heart attack or stroke and/or increased risk for vascular disease

  • Unexplained vaginal bleeding

  • Active or past breast cancer

  • Fibrocystic breast disease

  • Active liver disease

  • Endometrial cancer

  • Gall bladder disease or liver disease

  • High risk for blood clots or a history of blood clots


When are hormones unsafe?

Typically, the older a woman is, the greater the overall risk. The data is becoming clearer that women over age 60 should be aware of the increased risk of starting hormones because their risk of stroke starts to increase. Younger women who start BHT within five years of menopause may have more benefits with less risk. One prominent study by the World Health Initiative (WHI), revealed that women from age 50-59 taking estrogen were no more likely to have a heart attack or die of heart disease than those taking a placebo. Researchers even suggested that the risk for heart disease in this group might have been slightly reduced. Some risks associated with hormones include blood clots, stroke, and breast cancer. These complexities make it important to consult with your provider and tailor each treatment to the individual risks and benefits.


The Bottom Line--Is HRT safe? Is it beneficial?