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Benefits vs Risks of Bioidentical Hormone Replacement Therapy

Benefits vs Risks of Bioidentical Hormone Replacement Therapy Doctor Seattle & Bellevue

Bioidentical hormone replacement therapy risks and benefits must be weighed in every patient. To reduce the risks of bioidentical hormone replacement therapy (BHRT) the treatment must be customized to each individual patient’s needs and medical condition.

Femme Clinique’s Hormone Balancing Approach

Our guiding principles:

  • Treat the cause – you don’t have a Prozac® deficiency, but maybe you have a hormone imbalance or nutritional deficiency
  • Treat the whole person – helping you balance nutrition and lifestyle to support your body’s needs
  • Honor the healing powers of nature – help the body heal itself by balancing your hormones and supporting your body’s functions
  • Prevention – weigh risks and benefits of deficiencies of key health problems in the future (ie osteoporosis and breast cancer)
  • Doctor as teacher – we spend time with our patients to help guide them through the process of hormone balance and aging

The 8 Keys to Vitality After Menopause

  1. Balance stree in your life and practice mindfulness – read “The Power of Now” by Eckhart Tolle
  2. Eat a balanced diet and improve your blood sugar regulation – read “Nourishing Traditions” by Sally Fallon & Mary G. Enig, PhD
  3. Exercise regularly safely – read “PACE: Rediscover Your Native Fitness” by Al Sears, MD
  4. Sleep well – read “Brain Fitness: Anti-Aging to Fight Alzheimer’s Disease, Supercharge Your Memory, Sharpen Your Intelligence, De-Stress Your Mind, Control Mood Swings, and Much More” by Robert Goldman, MD, Lisa Berger, and Ronald Klatz, MD, DO, PhD
  5. Avoid toxins and promote detoxification by eating organic foods and using saunas (ask your doctor first)
  6. Do regular screening tests such as pap smears and breast thermography
  7. Monitor blood levels of key hormones and other markers to help improve your health and prevent disease
  8. Bioidentical hormone replacement therapy or hormone balancing, weighing your individual risks and benefits

What to expect at your first appointment

During your first appointment, we’ll review your medical history and determine what lab testing is needed. We’ll discuss our approach to balancing hormones and potential benefits and risks related to bio-identical hormone replacement. The first visit usually lasts about an hour and follow up visits are typically 15 – 30 minutes.

At your second visit we will discuss your treatment recommendations. We will also review the safety and potential risks and benefits of the therapy along with any questions you may have. Our treatments are concierge. This means that you can contact us and meet with Dr. Akiko as often as needed to discuss your treatment without additional cost.

Conventional Hormone Replacement Therapy (HRT) for Women

While some women choose not to treat hormone imbalances such as menopause, there are other women who prefer the more short term approach to reducing hot flashes during menopause. This treatment is typically recommended to be short term due to the well known risks such as blood clots and cancer.

If you open a textbook on physiology, how the body works, you will see that estrogen and progesterone effect almost every cell in your body and much more than just your hot flashes. The hot flashes are merely a symptom of a hormone deficiency, estrogen. Conventional hormone replacement therapy typically uses synthetic estrogen that is taken by mouth. The estrogen is altered so it can survive breakdown by your liver. This alien estrogen is different from any estrogen your body has ever made. Horse estrogens are also commonly used and these are also alien to your body. Thus, it makes sense that this approach to hormone replacement therapy has risks that may be greater than the benefits.

Benefits of Bioidentical Hormone Replacement Therapy (BHRT) for Women

Bioidentical hormone replacement therapy has been practiced for about 1,000. The Chinese used hormone preparations as documented by several texts from 1025 to 1833 AD. Humans are unique in that we live a large part of lives without the ability to reproduce. Most other animals die before losing their ability to reproduce. While we may be living longer our quality of life is diminishing in the United States.

Many doctors disagree on the best way to address the hormone decline that occurs with aging. Restoring your hormones to youthful levels is one approach. Bio-identical hormone therapy can help reduce the symptoms of menopause, such as:

  • Fatigue
  • Poor sleep
  • Low libido
  • Low mood
  • Social anxiety
  • Vaginal atrophy

Hormone deficiencies are related to a number of common symptoms, including menopause, headaches, weight gain, and mood swings. Learn more about the symptoms of hormone deficiencies

Bio-identical hormone replacement therapy can also help prevent other health problems such as:

  • Dementia
  • Heart disease
  • Osteoporosis
  • Diabetes
  • Some forms of cancer

It is your choice to replace and balance your hormones using bio-identical hormones and nutritional therapies. If you choose to receive bio-identical hormone replacement it is because you understand the risks and understand how we reduce these risks. Our goal is always to help improve the quality of your life in the safest manner. With any medical treatment there are risks. The following is an overview of the risks and benefits of balancing several key hormones with bio-identical hormone replacement.

Bio-identical refers to the structure of the molecule. Bio-identical hormones are molecularly identical to the hormones your body makes. These hormones are derived from natural sources (soy or wild yam). Plants produce hormones similar to ours that can be processed in a lab to become identical to our hormones – bio-identical. Bio is Latin for life.

Premarin® could be considered “natural” because it comes from a pregnant horse’s urine but its structure is different from our human hormones. Whenever possible we use human hormones because because your body knows what to do with them. Hormones convert into other hormones and this is very important. Horse hormones and hormones that are altered to prevent breakdown are associated with much higher risks.

It is important to consider how hormones convert to other hormones. For example, if a patient has breast cancer estrogen must not be used but testosterone with a medication to block its conversion to estrogen can help treat many symptoms such as vaginal atrophy (thinning). It is the outer portion of the vagina that can thin with low estrogen levels and research has shown that other hormones, such as testosterone or oxytocin, can be helpful. Topical testosterone can help treat vaginal atrophy and testosterone can convert to estrogen so if patient has breast cancer that is sensitive to estrogen this must be addressed.

Regular lab testing and screening exams can help reduce risks significantly. Certain hormones are considered to increase cancer risks and other hormones are related to decreased cancer risks. Some hormones promote bone health while others improve mental health. Many hormones, such as the key hormones estradiol, estriol, estrone, progesterone, oxytocin, thyroid, testosterone, and cortisol, effect your health on multiple levels. Progesterone improves sleep, reduces anxiety and sleep apnea, decreases the effects of estradiol (a type of estrogen) in your body, and reduces the negative effects of testosterone.

Our opinion is that the overall there is more data pointing towards safety and quality of life. The research is inconclusive in terms of cancer risks. One of the biggest studies ever done that included 80,377 postmenopausal women found that the type of hormone replacement therapy used made a significant impact on cancer risk. The combination of bio-identical estrogen with bio-identical progesterone had the least risk compared to other “alien” forms of these hormones such as synthetic progestins.

“We found that the risk of invasive breast cancer was significantly lower with estrogen–progestagen HRTs containing progesterone or dydrogesterone than with HRTs containing other progestagens. The latter group involved a variety of progestins whose associations with breast cancer risk did not differ significantly from one another. We also observed a significantly increased risk of breast cancer with the use of estrogen alone.”1

By using 24 hour urine hormone testing to measure the breakdown of your hormones we can measure over 30 different markers that help us improve safety and decrease risk. While we are always focused on increasing safety and reducing risks there are always some risks associated with any medical treatment. There are also risks associated with not treating hormone deficiencies. It is always a choice you have to make for yourself and we are here to support you.

There are some studies that point to higher incidences of breast cancer but in these studies they are not customizing the doses and treatment to the patient and, certainly, the lab testing is poor in our opinion.

Bioidentical Hormone Replacement and Pregnancy

If you are pregnant or planning on becoming pregnant you should notify us. This also includes breast feeding. Safety while breast feeding or during pregnancy cannot be guaranteed. You should consult your obstetrician or pedicatrician before using bio-identical hormones during pregnancy or while breast feeding.

If you become pregnant while on bio-identical hormone replacement you need to notify us immediately. Hormone balancing in younger women may increase fertility. If you are pre-menopausal and still have your ovaries and uterus it is important to use adequate birth control during bio-identical hormone replacement therapy.

The Risks of Bioidentical Hormone Replacement Therapy

The Risks and Benefits of Progesterone Replacement

Bio-identical progesterone can be taken by mouth in a capsule, under the tongue as a sublingual troche,
as suppositories, and in the form of a topical cream or gel. Progesterone taken as a pill can make you sleepy. Progesterone capsules should be taken before bed to help improve sleep.

“Progesterone is present in a wide spectrum of biological activity within a variety of tissues. This hormone is also known to affect reproduction, sleep quality, respiration, mood, appetite, learning, memory and sexual activity. Progesterone exerts a sleep induction or hypnotic effect and is a potent respiratory stimulant that has been associated to a decrease in the number of central and obstructive sleep apnea episodes in men. The literature also contains a substantial amount of data on the effect of apnea in women with obesity/hypoventilation during menopause.”2

One of the main actions of progesterone is to balance the effects of estrogen in your cells. During your menstrual cycle progesterone helps maintain your uterine lining to prevent bleeding. Estrogen causes growth of the uterine lining and progesterone prevents uncontrolled growth of these tissues. This is why if you have a uterus most doctors agree that progesterone is needed when you take estrogen during hormone replacement.

While balancing your hormones you may have some hormonal symptoms such bloating, breakthrough bleeding, missed menstrual cycles, breast swelling and tenderness, fluid retention changes, weight gain, sedation, and mood changes. If you experience any of these symptoms it is important to report them to us so we can adjust your hormone doses and do lab testing or physical exams if necessary.

The Risks and Benefits of Estrogen Replacement

Bio-identical estrogen should only be taken as a topical cream or gel for the best safety. This is to prevent the estrogen going through your liver when it first enters your system. Almost everything you eat is processed by your liver before it enters the rest of your body. Topical creams and gels travel through your entire body before they are processed by your liver. Typically, the best way to apply your hormones is in a small amount of concentrated cream on mucosal membrane (the labia minora). This way the hormones are coming from the same blood supply as they did when you produced them naturally. These hormones absorb very well through a mucosal membrane so only a small amount is needed to get a whole body effect.

Topical estrogen or other hormones combined with nutrients can be used topically on the face to improve skin quality. A 2007 study found that “topical estrogen associated to systemic estrogen therapy seems to increase the expression of skin collagen amount, which may prove to be beneficial for the postmenopausal facial skin.”3

There are several different types of estrogen that can be combined. Estradiol and estriol is the most common combination, with 70-80% estriol and 20-30% estradiol. Estradiol helps reduce many of the symptoms of menopause and estriol helps reduce cancer risks due to its ability to activate special estrogen receptors (estrogen receptor beta) known for their anti-cancer effects.

During hormone balancing with topical estrogen adverse reactions may occur, such as bloating, breakthrough bleeding, breast swelling and tenderness, fluid retention, weight gain, and mood changes. Women who use oral estrogen are at increased risk for liver cysts, death from blood clots and possibly cancer. High potency conjugated estrogens (e.g. Premarin), and perhaps even estradiol, have been associated with an increased risk of breast cancer and blood clots (the latter especially in smokers). Estriol may carry a lower risk of breast cancer and may even protect against breast cancer. Nonetheless, the whole area of estrogen replacement is undergoing further evaluation. Do not take estrogen if you have breast cancer.

A review published in the prestigious Maturitas journal in 2008 pointed out the differences between bio-identical hormone replacement using topical estrogen and conventional HRT which uses oral estrogen and progesterone in altered forms.4 Many of the side effects associated with estrogen replacement, such as increased stroke and breast cancer risks, are from studies that used oral estrogen, often in an altered synthetic form. The authors concluded after reviewing the available literature, “there is good observational data to suggest that HRT combining micronized progesterone to estrogens will not result in any increased incidence of breast cancer, in contrast to most synthetic progestins. Overall very long-term use of unopposed estrogens might still induce a very slight increase in BC risk.”4

Using progesterone with estrogen replacement appears to reduce the risks of breast cancer significantly. For some reason many doctors still think that progesterone is only necessary, in combination with estrogen replacement after menopause, if you have a uterus. This outdated view may put patients at increased risk for breast cancer if their doctor prescribe them estrogen only. Some patients may desire oral estrogen because they tried topical creams and didn’t notice any difference. The reason the cream didn’t help is likely because it didn’t absorb. Often, changing the base of the cream or gel will improve this and allow a patient to get the reduced risks of topical estrogen (compared to oral estrogen).

“Non-orally administered estrogens, minimizing the hepatic induction of clotting factors and others proteins associated with the first-pass effect, are associated with potential advantages on the cardiovascular system. In particular, the risk of developing deep vein thrombosis or pulmonary thromboembolism is negligible in comparison to that associated with oral estrogens. In addition, recent indications suggest potential advantages for blood pressure control with non-oral estrogens. To the same extent, a growing literature suggests that the progestins used in association with estrogens may not be equivalent.”4

Bio-identical hormones appear to have less risks than synthetic altered hormones and more benefits. This is likely because our bodies know what to do with bioidentical hormones because they’re identical to the ones our bodies make naturally. By supplementing these hormones and using 24 hour urine hormone testing we can see how these hormones are breaking down and balance their breakdown with other supportive treatments, such as nutritional therapies.

“Recent evidence indeed shows that natural progesterone displays a favorable action on the vessels and on the brain, while this might not be true for some synthetic progestins. Compelling indications also exist that differences might also be present for the risk of developing breast cancer, with recent trials indicating that the association of natural progesterone with estrogens confers less or even no risk of breast cancer as opposed to the use of other synthetic progestins.”4

In our opinion, the safest and most effective hormone replacement treatment needs to be customized to the patient’s needs. Individualized medicine is the wave of the future. Someday we will be able to include genetic testing to further determine where best to support the body to reduce risks and increase benefits.

“In conclusion, while all types of hormone replacement therapies are safe and effective and confer significant benefits in the long-term when initiated in young postmenopausal women, in specific clinical settings the choice of the transdermal route of administration of estrogens and the use of natural progesterone might offer significant benefits and added safety.”4

The Risks and Benefits of Testosterone Therapy in Women

Bio-identical testosterone therapy for women at low doses can be a safe and effective treatment for many post-menopausal symptoms such as low libido and loss of muscle mass. Bioidentical testosterone can be taken as a sublingual troche, a topical cream, or as a low dose subcutaneous injection. Topical creams are usually applied daily. Sublingual testosterone can be taken on an as needed basis for sexual enhancement. Testosterone injections can be done using an very small insulin needle just under the skin and are usually only needed once to twice per week.

Side effects from testosterone therapy are generally mild when they occur. Possible but rare side effects of testosterone therapy in women include acne, change in libido, angina or heart attacks, hirsutism (facial hair growth) and scalp hair loss (or growth), clitoral enlargement, voice changes, or water retention. If using a formulation of testosterone that is applied to the skin or injected, a local irritation may occur. In women, excessive testosterone or DHEA doses could increase the risk of diabetes or facial hair. It is important to report any side effects as soon as possible so we can determine the cause and modify your treatment as needed.

A 2012 review of the current research on testosterone therapy for women with low libido, published in the Journal of Sexual Medicine, concluded that testosterone therapy is safe for postmenopausal women using a low daily topical dose.5 Hypoactive sexual desire disorder (HSDD) is the technical term for low libido or low sex drive. Low sex drive can certainly be caused by other things besides low testosterone levels. Testosterone therapy appears to have important effects on other aspects of your health as well and may reduce the risks of estrogen replacement further.

“Randomized, double-blind, placebo-controlled studies have established the efficacy of the transdermal testosterone patch for relieving symptoms of HSDD in surgically and naturally menopausal women with and without concomitant estrogen or estrogen/progestin therapy. The main side effects reported in clinical trials were increased hair growth and acne. Available safety data for testosterone, although not conclusive, were reassuring with respect to cardiovascular, breast, and endometrial outcomes. Interim data from a long-term phase III safety trial of a testosterone gel demonstrate a continued low rate of cardiovascular events and breast cancer in postmenopausal women at increased cardiovascular risk.”5

The Risks and Benefits of Oxytocin Therapy

Oxytocin is a hormone produced by your body naturally that can decline with age. Oxytocin deficiency is associated with a number of health problems, including:

  • Menopause & Surgical Menopause7
  • Prolonged Stressful Situations8
  • Hypothyroidism9
  • Depression10
  • AIDS11
  • CMV infection12
  • Multiple Sclerosis13
  • Fibromyalgia14
  • Anorgasmia – inability to have an orgasm during sex6
  • Chronic Opioid Use15
  • Parkinson’s Disease16
  • Prader Willi Syndrome17-19
  • Feelings of Loneliness20
  • Anxiety Disorders21
  • Certain forms of Schizophrenia22
  • Autism23-24

Oxytocin is a hormone that your body produces naturally. Research has shown that by taking oxytocin you may actually increase your natural production. This is why only very small amounts are needed to produce a therapeutic effect.

“It remains to be shown how exactly intranasally administered OT enters into the brain or starts to influence brain neural activity along other pathways, and whether the effects are visible during at least 7h not only in saliva but also in pertinent brain areas. The feed forward mechanism of the oxytonergic system, leading to more production of oxytocin with increased OT levels, may play an important role in the explanation of the persistently high OT levels. In natural circumstances, human lactation has been suggested to be subject to such a feed forward mechanism …”25

Oxytocin can be taken as a sublingual tablet, microdot, or troche. Sublingual means under the tongue. It can also be compounded into a nasal spray, topical gel or cream, or injection. The safest route appears to be sublingual or intranasal (nasal spray). Oxytocin injections can be very dangerous as an overdose can cause brain hemorrhage. It is impossible to have this happen with intranasal or sublingual oxytocin because the doses are very small and only a small amount can enter your system. If you swallow your oxytocin it will likely be destroyed by your stomach acid.

“For a long time, oxytocin was regarded as a pregnancy hormone released by the hypophysis [brain] to stimulate labour and milk ejection.”26

“It is now known that oxytocin receptors can occur almost ubiquitously in the organism, that oxytocin is also formed outside of the brain and that oxytocin has functions in a number of organs.”26

Oxytocin is becoming a target for drug companies as well who will likely seek patents on new drugs to effect oxytocin and its receptors. “OXT and AVP are emerging as targets for novel treatment approaches — particularly in synergistic combination with psychotherapy — for mental disorders characterized by social dysfunction, such as autism, social anxiety disorder, borderline personality disorder and schizophrenia.”27
Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine. Meyer-Lindenberg A, Domes G, Kirsch P, Heinrichs M. Nat Rev Neurosci. 2011 Aug 19;12(9):524-38. doi: 10.1038/nrn3044.

“It is concluded that a sniff of oxytocin can change emotion perception and behavior in trusting relationships.”28

“The evidence shows that intranasal oxytocin: (1) produces no detectable subjective changes in recipients, (2) produces no reliable side-effects, and (3) is not associated with adverse outcomes when delivered in doses of 18-40 IU for short term use in controlled research settings.”29

“Oxytocin seems to enhance the buffering effect of social support on stress responsiveness. These results concur with data from animal research suggesting an important role of oxytocin as an underlying biological mechanism for stress-protective effects of positive social interactions.”30

One potential side effect oxytocin therapy is a decrease in the production of your stress hormone, cortisol. The symptom of low cortisol that you would likely notice is fatigue and/or lower blood sugar levels. This is why we typically check and balance cortisol levels in every patient. The adrenals glands produce cortisol and after menopause they take over a lot of the work the ovaries were doing in terms of hormone production.

“This is the first study to demonstrate that the effect of intranasal oxytocin on salivary cortisol is dose-dependent, and that intranasal oxytocin attenuates cortisol levels in response to physical stress.”31

Headaches may also occur during oxytocin therapy but this is rare. This is likely due to low blood sugar or over-use of the oxytocin. Patients who are sensitive should start with very low dose and increase their dose slowly over time if needed. Talk to your doctor before changing the doses that your doctor recommended. By prpviding feedback of how your feeling we can help you fine tune your dose. Some patients may notice little difference initially. Some women notice very potent effects initially so it is important to follow our doctor’s recommendations in terms of dosage.

The Risks and Benefits of Thyroid Supplementation

Your thyroid is a small gland located in your neck that receives signals from your brain to produce small amounts of thyroid hormone. The signal from your brain is called thyroid stimulating hormone (TSH) and hormones your thyroid produces are called triiodothyronine (T3) and thyroxine (T4). The bio-identical hormone versions of T3 is liothyronine (Cytomel®). The bio-identical T4 available is levothyroxine (Synthroid®). T4 converts to T3 to become active. Some people are unable to convert the T4 to T3 effectively. Most doctors prescribe only T4 and monitor only by checking TSH levels.

“TSH levels used to monitor substitution, mostly regulated by intracellular T3 in the pituitary, may not be such a good indicator of adequate thyroid hormone action in all tissues. The co-administration of T3 may prove more effective in this respect, provided novel suitable preparations are developed. Until this is accomplished, substitution in hypothyroidism should aim at low normal TSH, to ensure normal T3 levels.”32

It is important to monitor TSH levels but also important to monitor symptoms and T3 and T4 levels. Low thyroid function (hypothyroidism) is often missed by doctors or improperly treated due to reliance on TSH levels. Our goal is to work with you to resolve your symptoms and improve your quality of life by using your symptoms AND thyroid hormone levels to monitor your treatment.

Subclinical hypothyroidism is a common condition that is often missed by only checking TSH levels. Some patients may have a normal TSH but a low T3 or T4 level. Patients who have been diagnosed with low thyroid problems but see little results from treatment need to have their T3 and T4 levels checked. A compounded slow release T3/T4 combo or dessicated thyroid medication may be more beneficial than T4 alone.

“The substitution of L-T(3) for L-T(4) at equivalent doses (relative to the pituitary) reduced body weight and resulted in greater thyroid hormone action on the lipid metabolism, without detected differences in cardiovascular function or insulin sensitivity.”33

Proper thyroid replacement can reduce the symptoms of hypothyroidism that can include difficulty losing body fat, fatigue, brain fog, and water retention. There are many more potential symptoms of low thyroid function and research is unclear on the long term benefits that may include improved longevity. Some doctor may just write off your symptoms as a “normal” part of aging and perhaps offer you an anti-depressant.

“Thyroid disease in the elderly can be easily overlooked. Not uncommonly, it appears in an atypical manner, and the classic symptoms are often absent. Symptoms are too often explained as normal aging process or attributed to coexisting diseases.”34

While low thyroid is more common, high thyroid (hyperthyroidism) can also occur and may require treatment from a specialist. It is important to report any concerning symptoms to us and take your medication as prescribed. Over-use of thyroid can lead to rapid heart rate that may require emergency care.

Potential side effects in using thyroid medication include osteoporosis, palpitations, dizziness, psychiatric problems (mania), and heart beats so fast that you could pass out or end up hospitalized. This is why when you begin thyroid treatment we start with a low dose and slowly increase your dose to improve your symptoms while giving your body time to adjust. Starting at too high a dose is more likely to lead to rapid heart rate.

It is important to have a comprehensive approach to balancing to hormones to minimize potential harm. For example, while there is a slight increased risk of bone loss from thyroid replacement we can reduce this risk by balancing your estrogen and testosterone levels. Adequate estrogen and testosterone and linked to better bone health.

In general, it is best to take your thyroid medication on an empty stomach. Some doctors say that taking thyroid medication in the morning is best. It is important to avoid drinking coffee 30 minutes before or after you take your thyroid medication. Thyroid levels are naturally highest in the afternoon so we typically recommend taking your thyroid medication around 4pm or an hour before dinner. This is a good time to take your thyroid medication because it is away from food and coffee.35 If you notice problems falling asleep please advise your doctor. If this occurs you may need to take your thyroid medication in the morning.

The Risks and Benefits of Balancing Cortisol

Your adrenal glands are located above your kidneys in your body. These tiny glands produce several different hormones including your stress hormones, cortisol and cortisone. Cortisone is the storage form of cortisol. Most patients have taken synthetic forms of cortisol in the form of anti-inflammatory medications, such as prednisone (a synthetic steroid form of cortisol). Prednisone is synthetic and much more potent than your natural cortisol. If you are taking prednisone or a similar medication, it is important to work with your doctor if you wish to change your dose as stopping too quickly can be life-threatening.

In general, most patients with adrenal problems fall more into a grey area where there levels are considered “normal” but need improvement. To determine the best approach to balancing adrenal gland function a number of lab tests may be used.

Loss of cortisol in the urine has been associated with increased severity in autism and other health problems. Urine allows us to see how the hormones are breaking down in your body over a 24 hour period. Blood and saliva can be useful but are just snapshots of hormone levels.

“These data suggest that altered cortisol excretion pattern and high level of corticosteroids in urine may probably be a consequence of altered hypothalamic-pituitary-adrenal axis function, which may contribute to the pathogenesis and affect the severity of autism.”36

Cortisol levels are naturally highest in the morning and then decline throughout the day, a diurnal (daily) rhythm. By using saliva we can measure cortisol levels several times from waking to sleep and even during the night. If your cortisol levels are too low in the morning it is likely you will be tired in the mornings and feel better when you “sleep in”. While sleeping more can be very helpful, improving cortisol levels requires a change in life-style as stress is a major cause of cortisol deficiency.

“These findings suggest that the diurnal rhythm and awakening response of salivary cortisol is significantly reduced in older adults and that variations in the cortisol diurnal rhythm of younger adults are associated with dietary factors. Younger adults with a poor quality of food intake may be vulnerable to a reduction in the amplitude of the cortisol diurnal profile and this may have implications for other aspects of health.”37

Salivary cortisol is very convenient but unfortunately provides poor testing for other hormones such as testosterone. It can be useful for checking progesterone levels in women not on hormone replacement therapy. Some doctors try to use saliva testing exclusively because it is cheaper and easier but this is a poor option to ensure safety and efficacy of bioidentical hormone replacement therapy.

“Although salivary testing of [Testosterone] concentrations is an appealing alternative because it is inexpensive and noninvasive, our results do not support the routine use of salivary [Testosterone] levels in postmenopausal women.”38

“The diagnostic value of salivary oestradiol, progesterone, testosterone, dehydroepiandrosterone and aldosterone testing is compromised by rapid fluctuations in salivary concentrations of these steroids.”39

Blood cortisol or urine cortisol testing may look “normal” while there can be severely altered pattern of cortisol production. Some patients may produce too little cortisol in the morning and too much in the evening. This is important when determining the best treatment options.

The term “adrenal fatigue” has a very bad reputation in the medical world for unknown reasons. While “adrenal fatigue” is synonymous with “hypocortisolism” and “cortisol deficiency”, these are the terms that are used in the literature. All these terms are referring to a partial lack of cortisol.

“Based on the reviewed findings, we propose that a persistent lack of cortisol availability in traumatized or chronically stressed individuals may promote an increased vulnerability for the development of stress-related bodily disorders. This pathophysiological model may have important implications for the prevention, diagnosis and treatment of the classical psychosomatic disorders.”40

Mental and emotional problems are associated with cortisol deficiency. In severe situations the replacement of bio-identical cortisol (hydrocortisone) may be necessary. In cases of extreme cortisol deficiency death may occur. This is called an Addisonian Crisis and can occur if you abruptly discontinue prescription medications such as prednisone and hydrocortisone. Cortisol deficiency has even by shown to cause psychiatric disorders, with cases of cortisol replacement leading to reversal of their mental disorder.

“Generally, an appropriate comprehensive examination supported a diagnosis of cortisol insufficiency. For the most part, these patients were successfully treated with physiologic doses of bio-equivalent hydrocortisone, along with replacement of any other deficient hormone. By correcting underlying hormonal insufficiencies, many patients improved, with some patients having a total reversal of psychiatric symptoms. It is therefore reasonable to evaluate and treat hormonal insufficiencies with hormones prior to using psychotropic medication.”41

In situations where cortisol replacement is necessary, taking smaller doses three times throughout the day is likely to provide the most benefit with the least amount of risk. This will prevent your cortisol levels from dropping too low or going to high. A higher dose is usually taken first thing in the morning and then two lower doses at noon and in the evening.

“Thrice-daily dosing resulted in less frequent and prolonged hypocortisolemia than twice-daily regimens, but we were unable to relate either regimen to acute clinical end points of glycemia, lethargy, or cognitive function.”42

There are several ancient remedies to adrenal fatigue. The Chinese used bioidentical hormone replacement over 1000 years ago. In India, healers have been using medicinal plants to slow the aging process for thousands of years.

“The roots of Withania somnifera (WS) are used extensively in Ayurveda, the classical Indian system of medicine, and WS is categorized as a rasayana, which are used to promote physical and mental health, to provide defence against disease and adverse environmental factors and to arrest the aging process.”43

Ashwaganda, Withania somnifera, is considered an adaptogen in herbal medicine. Adaptogens are made by plants and help our bodies improve stress responses and adapt to our environment.

“Plant adaptogens are compounds that increase the ability of an organism to adapt to environmental factors and to avoid damage from such factors. The beneficial effects of multi-dose administration of adaptogens are mainly associated with the hypothalamic-pituitary-adrenal (HPA) axis, a part of the stress-system that is believed to play a primary role in the reactions of the body to repeated stress and adaptation.”44

Side effects of replacement of cortisol with prescription hydrocortisone (Cortef®) can occur. These side effects can include decreased immune function, poor sleep, increased hunger, and anxiety. These are symptoms of excess cortisol and if they occur it is important to report them so your treatment can be adjusted appropriately. Elevated cortisol levels for prolonged levels can increase the risk of diabetes, osteoporosis, and Cushing’s Syndrome. There is also an increased risk of bleeding in your intestines with the use of Cortef®. Due to these potential side effects we rarely use Cortef® and if used for the shortest time possible.

Side effects from nutritional and herbal approaches to balancing cortisol levels are uncommon but excess cortisol can occur. Certain herbs such as licorice can increase cortisol levels significantly. It is important to notify us if you change your supplements or medications on your own or by working with another doctor. Be sure to have your primary care doctor check your blood pressure regularly. We recommend having a blood pressure cuff at home so you can check your blood pressure when you are relaxed.

Some patients may also be sensitive to certain herbs. If you notice any negative changes during your treatment it is important to notify us. Coffee stimulates cortisol production. It is important to avoid coffee in the afternoon or as otherwise recommended by your doctor.

Risks and Benefits of Bio-identical DHEA Supplementation

Known as the hormone of anti-aging and “mother hormone”, it is a precursor to testosterone, estrogen, and progesterone. Dehydroepiandrosterone (DHEA) is a powerful hormone that can help increase libido, improve immunity, increase energy, and improve mood and memory. DHEA supplementation may help with weight loss.

A 2012 study, in the Journal of Clinical Endocrinology, found that an “oral dose of DHEA-S is useful for weight loss. In obese postmenopausal women, the hormone significantly improves plasma biochemical levels and anthropometric characteristics, leading to a better metabolic profile, which highlights the usefulness of this therapy against metabolic syndrome in this group of women.”45

DHEA is usually taken as a topical cream to avoid passing through the liver before it enters the rest of your body. Sometimes oral DHEA is used as it can be more convenient. If it is being applied to the skin you should apply it to the abdomen, inner arms, or inner thighs. It is important to rotate the location where you apply the cream to prevent a decrease in absorption through the skin.

If you get acne please contact us. You may need to discontinue it until the acne clears. You can then typically start using it again, after the acne clears, at a lower dose. Side effects may include acne, increased libido, aggression, and abnormal hair growth. These symptoms will usually disappear quickly after discontinuing use of the DHEA cream. Please call our office with any questions or concerns.

How to take a sublingual medication

Oxytocin is typically taken in a sublingual form. Other medications and hormones can also be taken sublingually. By taking a medication or hormone under the tongue you are bypassing the stomach and allowing it to enter your blood, directly. This can increase the speed that you feel the effects. Medications such as apomorphine and Viagra® can be taken under the tongue on an as needed basis for sexual enhancement.

When taking sublingual medications it is important to ensure your mouth is well hydrated (wet). If your mouth is dry or you have little saliva, drinking a glass of water before using the sublingual medication can help. Place the prescribed amount under your tongue and try to keep it there, allowing it to dissolve, for about 15 minutes if possible. It is okay to swallow some of the sublingual medication as this will occur.

If you do not feel any effects from the sublingual medication within an hour it may be okay to take an additional dose. Please consult us before doing this though. Your sublingual medication is likely in the form of a square with four quarters. Each of these quarters is considered one dose. Please ask us about this if you are unsure what dose you are supposed to be taking.

How to use the topical hormone creams

Topical gels or bioidentical hormone cream are applied with a pre-measured syringe to the stomach, inner thighs or inner arms and are absorbed through the skin, directly into the blood stream. Some gels or creams are designed for vaginal use. Patches, like bioidentical hormone cream and gels, allow direct skin absorption throughout the day.

How to measure from a 1ml syringe

Topical estrogen, Biest, is applied typically to the inner labia because it is mucosal membrane. The dose used is very small. If you are finding a mess in your pants from the topical cream you are likely using too much. Please contact us if you have any question about how to measure these hormones.

How to avoid transfer of the topical hormone creams to others

Make sure to wash your hands well after applying your hormone creams. It is important to avoid transfer of the creams to your spouse, children, pets and others you may touch. In general, washing your hands well with hot water and soap will be sufficient. Scrubbing around the fingernails is almost important.

Avoid using estrogen and other hormone creams during sexual intercourse. Breast enlargement can occur in men regularly exposed to estrogen. Taking a shower and washing off hormone creams from the skin before sex is important to avoid transfer.

When will your symptoms resolve?

In our experience every patient responds differently. Certain symptoms, like night sweats and hot flashes, can disappear in a
few weeks. Decreased sex drive (low libido) can be due to a variety of problems, such as fatigue, and may take several months to improve significantly. For example, thyroid hormone replacement takes 7-8 weeks just to achieve stable blood levels. We appreciate your patience.

To ensure your safety during hormone replacement therapy we typically do more lab testing initially will we help you determine your optimal hormone doses and supplementation. Once balance is achieved we typically do lab testing once to twice a year to check your levels. To be a patient at Femme Clinique you must do the minimum amount of lab testing to ensure your safety. You must also do regular screening tests for breast and gynecological health.

Thermography is an alternative to mammography. Regular pap smears and breast exams are important as well. Self breast exams should be done on a regular basis. Please ask us if you are unsure how to do a self breast exam.

You must have a primary care physician, gynecologist, or other practitioner to help you coordinate these screening exams. We may recommend additional screening tests as well. While we are assisting you with your hormone replacement therapies, you must still have a primary care physician for other health problems. We may refer you to your primary care physician or a specialist during your treatment for further evaluation.

You must report any adverse reaction or problem that might be related to your therapy. Our goal is always to minimize risks and increase benefits of your treatment. As you have read, there are some risks associated with bioidentical hormone replacement therapy. There are potential complications to bioidentical hormone replacement therapy and there are risks as well as to not being treated with bioidentical hormone replacement therapy. If you have any questions about these risks and how we are addressing them in your treatment it is important that you tell us.

Allergic reactions to topical hormone creams or other medications

Allergic reactions to topical hormone creams are rare. If you notice a rash, itching, or redness please contact us so we can determine the cause. Severe allergic reactions are very rare. Symptoms of severe allergic reactions can include difficulty breathing. If you experience shortness of breath or wheezing seek medical attention. In emergency situations call 911.

Please contact us at (425) 274-2777 with any questions or to make an appointment with Dr. Akiko.


The above claims have not been evaluated by the FDA. Many hormone treatments are off-label or don’t require FDA approval because they are bio-identical. This article is for information purposes only. Any treatments or changes to your medical care should be supervised by a physician.

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