Bioidentical Progesterone: Its Role in Hormonal Balance, Brain Health, Sleep, and Immune Regulation

Understanding progesterone, allopregnanolone, estrogen balance, mast cells, and the whole-person approach to hormonal health

By Dr. Margaret Christensen, MD

Introduction: Progesterone Is More Than a Reproductive Hormone

When most women think about progesterone, they think about pregnancy, menstrual cycles, or menopause.

But progesterone does much more than prepare the uterus for pregnancy.

It participates in an interconnected network of biological processes involving the brain, nervous system, reproductive organs, and other tissues.

During my decades of practice as an obstetrician-gynecologist and functional medicine physician, I became increasingly interested in how changes in progesterone signaling may influence symptoms extending far beyond the reproductive system.

Women often describe problems that seem unrelated:

• Difficulty falling asleep or staying asleep.
• Increased anxiety or irritability.
• Changes in menstrual bleeding.
• Hot flashes and night sweats.
• Brain fog and reduced concentration.
• Breast tenderness.
• Headaches or migraines.
• Changes in histamine-related symptoms.

Some of these concerns may be influenced by hormonal transitions, while others can have additional medical causes.

In functional medicine, I encourage looking at the relationships among different physiological systems rather than evaluating every symptom in isolation.

Progesterone is one of the hormones that illustrates why this systems-oriented approach can be valuable.

To understand its broader effects, we need to begin with basic steroid hormone biochemistry.

1. Understanding Progesterone: Where Does It Come From?

Progesterone is a steroid hormone synthesized from cholesterol.

Cholesterol is the starting material for the production of multiple steroid hormones, including progesterone, cortisol, aldosterone, testosterone, and estrogens.

This does not mean that increasing dietary cholesterol automatically raises progesterone levels. Steroid hormone production is regulated by a complex network of enzymes, signaling pathways, and endocrine feedback mechanisms.

The Cholesterol–Pregnenolone Pathway

The first major step in steroidogenesis involves conversion of cholesterol into pregnenolone.

Pregnenolone can then participate in different steroid-producing pathways.

One pathway leads to progesterone.

Other pathways contribute to androgen and estrogen synthesis.

Progesterone itself can also serve as a precursor in pathways involved in producing certain corticosteroids.

These pathways illustrate an important principle:

Reproductive hormones and stress-related hormones are connected biochemically, even though their production is controlled by different tissues and regulatory signals.

Where Is Progesterone Produced?

Before menopause, progesterone is produced primarily by the corpus luteum following ovulation.

During pregnancy, the placenta becomes an important source of progesterone.

Smaller quantities of progesterone or related steroids may also be synthesized in adrenal and other tissues.

What Happens During the Menstrual Cycle?

During the first part of the menstrual cycle, progesterone concentrations are relatively low.

After ovulation, the corpus luteum produces substantially more progesterone.

This produces the characteristic rise during the luteal phase.

If pregnancy does not occur, corpus luteum function declines, and progesterone concentrations fall.

These changes influence the endometrium and contribute to the normal menstrual cycle.

When ovulation becomes irregular, progesterone production can become less predictable.

This is particularly relevant during perimenopause.

2. What Does Bioidentical Progesterone Mean?

The term bioidentical refers to a hormone with the same molecular structure as the hormone naturally produced by the human body.

Bioidentical progesterone is chemically identical to endogenous progesterone.

It is different from many synthetic progestins, which have modified chemical structures.

Progesterone vs. Progestins

The word progestogen describes a broader category of substances that produce progesterone-like effects.

This category includes natural progesterone and multiple synthetic progestins.

Synthetic progestins vary in their chemical structures, receptor activities, metabolic properties, and clinical effects.

They should not all be treated as one identical substance.

Why Margaret Emphasizes the Distinction

In my clinical practice, I have emphasized the importance of understanding which hormone is actually being prescribed.

Natural progesterone and a synthetic progestin are not always interchangeable from a biochemical perspective.

Some synthetic compounds also interact with androgenic, glucocorticoid, or mineralocorticoid receptors.

These differences can affect individual tolerability and clinical outcomes.

I believe patients deserve to understand these distinctions when discussing hormone therapy.

Bioidentical Does Not Mean Risk-Free

The molecular structure of a hormone does not establish that every formulation, dose, route, or duration of treatment is safe.

Risks depend on the individual's medical history and the treatment being used.

Bioidentical progesterone is available in FDA-approved prescription products as well as compounded preparations.

Those categories have important differences in manufacturing oversight and clinical evidence.

3. Progesterone, Allopregnanolone, and the Brain

One of the most fascinating aspects of progesterone physiology involves its conversion into neuroactive metabolites.

Progesterone can undergo metabolism through pathways involving 5α-reductase and related enzymes.

An important downstream metabolite is allopregnanolone.

What Is Allopregnanolone?

Allopregnanolone is a neuroactive steroid that modulates the activity of GABA-A receptors.

GABA, or gamma-aminobutyric acid, is the principal inhibitory neurotransmitter in the adult central nervous system.

GABA-related signaling helps regulate neuronal excitability.

Allopregnanolone acts as a positive allosteric modulator of GABA-A receptors, enhancing certain inhibitory effects.

This mechanism has important implications for mood regulation, stress responses, and sedation.

Why This Is Relevant to Sleep

Oral micronized progesterone undergoes first-pass metabolism, producing several neuroactive metabolites.

Some women experience sleepiness following oral progesterone administration.

Clinical studies have examined potential benefits involving sleep onset, sleep continuity, and selected menopausal symptoms.

Responses vary, and progesterone is not a universal treatment for insomnia.

Margaret's Clinical Perspective

During my clinical career, I found oral micronized progesterone particularly interesting for selected women experiencing sleep difficulties during hormonal transitions.

My interest was based partly on its relationship with allopregnanolone and GABA-related signaling.

I have observed women reporting improved sleep and a greater sense of calm after appropriately prescribed treatment.

These clinical observations helped shape my preference for considering progesterone physiology when evaluating sleep complaints during perimenopause.

However, difficulty sleeping may also reflect sleep apnea, medication effects, anxiety, pain, thyroid disease, or other conditions requiring their own evaluation.

What About Brain Fog?

Progesterone metabolites interact with nervous-system signaling, and neurosteroids are being investigated for potential effects on neurological function.

However, a complaint of brain fog does not establish progesterone deficiency.

Cognitive symptoms should be evaluated within the broader medical picture.

4. Perimenopause: Why Progesterone Patterns Change

Perimenopause is the transition leading toward menopause.

During this period, ovarian function becomes increasingly variable.

Some menstrual cycles remain ovulatory, while others may not involve ovulation.

Because the corpus luteum forms after ovulation, anovulatory cycles do not produce the usual luteal progesterone rise.

This can contribute to changes in menstrual patterns and hormonal signaling.

Symptoms Women May Experience

Perimenopause can involve:

• Irregular menstrual cycles.
• Heavy or unpredictable bleeding.
• Night sweats and hot flashes.
• Sleep difficulties.
• Mood changes.
• Breast tenderness.
• Headaches.
• Changes in sexual and reproductive health.

Not every symptom is caused exclusively by low progesterone.

Estrogen fluctuations, aging, sleep disruption, medications, thyroid conditions, and other factors may also contribute.

Why I Evaluate the Whole Picture

In functional medicine, I consider menstrual patterns, sleep quality, stress physiology, nutrition, environmental concerns, and other relevant medical findings.

A single hormone measurement may not capture the complexity of a changing menstrual cycle.

The history and timing of symptoms can be extremely important.

Progesterone and Menopausal Hormone Therapy

When systemic estrogen therapy is prescribed to a woman with a uterus, adequate endometrial protection is essential.

Progesterone or another appropriate progestogen may be used for this purpose.

The choice of treatment, formulation, and regimen requires individualized medical assessment.

5. Progesterone and Stress: Understanding the HPA Axis

The hypothalamic-pituitary-adrenal axis, or HPA axis, coordinates important stress-related hormonal responses.

This system interacts with reproductive physiology through multiple signaling pathways.

What Happens During Chronic Stress?

Prolonged psychological or physiological stress may influence sleep, appetite, autonomic function, menstrual patterns, and reproductive signaling.

Severe stress, inadequate energy availability, and certain illnesses can interfere with ovulation.

When ovulation is disrupted, progesterone production during the expected luteal phase may be reduced.

The Concept of Progesterone Steal

In functional medicine discussions, the terms pregnenolone steal or progesterone steal are sometimes used to describe the idea that the body prioritizes cortisol production during stress at the expense of reproductive hormones.

This is a simplified clinical model rather than a demonstrated universal mechanism in which adrenal glands literally drain circulating ovarian progesterone.

The adrenal and ovarian steroidogenic pathways have distinct regulatory controls.

Nevertheless, I consider the interaction between stress physiology and reproductive hormone patterns clinically important.

The more precise question is how illness, stress, nutritional status, and endocrine regulation may contribute to changes in ovulation or hormone production.

Recognizing Different Causes of Fatigue

Fatigue during a stressful period does not automatically indicate adrenal failure.

True adrenal insufficiency is a specific medical disorder requiring appropriate evaluation.

Sleep disorders, anemia, thyroid disease, medications, depression, and other conditions may also contribute.

6. Estrogen Dominance: What Does the Term Mean?

Estrogen dominance is frequently used in functional and integrative medicine.

It commonly refers to a proposed imbalance in the relationship between estrogen activity and progesterone activity.

It does not have one universally standardized laboratory definition.

Absolute vs. Relative Hormone Changes

A woman may have changing progesterone production during anovulatory perimenopausal cycles while estrogen concentrations continue to fluctuate.

In this setting, some functional medicine practitioners describe the pattern as relatively unopposed estrogen activity.

The concept should not automatically be interpreted as proof that estrogen concentrations are excessively high.

Margaret's Clinical Observations

In my practice, I have considered this estrogen-progesterone relationship when evaluating women with irregular or heavy periods, breast tenderness, and other hormone-related concerns.

I also believe it is important to consider environmental endocrine-active compounds and individual differences in hormone metabolism.

However, these symptoms can have many other causes.

For example, heavy menstrual bleeding may result from fibroids, polyps, anovulation, adenomyosis, medication effects, or other conditions.

Why Endometrial Health Matters

Estrogen stimulates endometrial proliferation.

Progesterone helps transform the endometrium during the luteal phase and counterbalances some proliferative effects.

Prolonged unopposed estrogen exposure can increase endometrial hyperplasia risk.

Appropriate evaluation of abnormal bleeding is therefore essential.

7. Environmental Endocrine Disruptors and Hormonal Signaling

One of the central themes in my environmental medicine work is that hormone signaling can be influenced by substances encountered outside the body.

Certain environmental chemicals are described as endocrine-disrupting chemicals, or EDCs.

These include some bisphenols, phthalates, pesticides, and other compounds.

How Endocrine Disruptors Work

Depending on the chemical, endocrine disruption may involve changes in:

• Hormone receptor signaling.
• Hormone synthesis.
• Metabolic conversion.
• Transport proteins.
• Hormone elimination.
• Regulatory feedback mechanisms.

Different substances act through different pathways.

A chemical's ability to interact with a receptor does not establish that every ordinary exposure causes a clinical hormonal disorder.

Actual effects depend on dose, timing, exposure duration, and the individual's biology.

Mycotoxins and Hormone Receptors

Certain fungal metabolites have documented endocrine activity.

Zearalenone, for example, is recognized for its estrogenic properties.

However, not all mycotoxins behave as estrogen receptor agonists, and their toxicological profiles differ.

My clinical interest lies in understanding how environmental exposures may add complexity to an already sensitive endocrine system.

Practical Environmental Considerations

When relevant, patients and clinicians may review occupational exposures, drinking-water concerns, household chemicals, and other meaningful sources.

The goal is sensible exposure reduction rather than the impossible elimination of every environmental chemical.

8. Progesterone, the Gut Microbiome, and Estrogen Metabolism

Another important area of research concerns the interaction between intestinal microorganisms and hormone metabolism.

The term estrobolome is sometimes used to describe the collection of microbial genes capable of influencing estrogen metabolism.

Estrogen Conjugation and Enterohepatic Cycling

Estrogen metabolites can undergo conjugation during normal metabolism.

Certain intestinal bacterial enzymes, including beta-glucuronidase, can remove glucuronide groups from some compounds.

This may influence their potential for intestinal reabsorption.

The magnitude and clinical importance of these interactions depend on multiple factors.

Gut Health and Hormonal Symptoms

Researchers continue investigating whether changes in microbiome composition contribute to differences in circulating estrogen concentrations or hormone-related conditions.

This is an evolving field.

Margaret's Clinical Perspective

I have long considered gastrointestinal health as part of my functional medicine evaluation of hormonal symptoms.

Digestive function, nutrition, liver metabolism, and microbial activity can all be relevant to overall physiology.

However, a diagnosis such as endometriosis cannot be established or excluded from measures of intestinal permeability, microbiome composition, or beta-glucuronidase alone.

Endometriosis Requires Its Own Evaluation

Endometriosis is a complex inflammatory, hormone-responsive condition.

It should not be reduced to the presence of gut dysfunction.

Individuals with persistent pelvic pain, painful menstruation, infertility, or related symptoms deserve appropriate gynecological assessment.

9. Progesterone, Mast Cells, and Histamine

Mast cells are immune cells involved in allergic responses, inflammatory signaling, and tissue surveillance.

They contain mediators including histamine.

Researchers have investigated interactions between sex hormones and mast-cell activity.

Can Estrogen Affect Mast Cells?

Experimental studies suggest that estrogen-related signaling can influence mast cells under certain conditions.

Some patients also report changes in allergy-like or histamine-related symptoms across their menstrual cycles.

These observations have stimulated interest in the relationship between sex hormones and immune regulation.

What About Progesterone?

Progesterone and its metabolites interact with multiple biological systems.

Experimental research has explored potential effects on immune signaling and mast-cell responses.

However, describing progesterone as a universally effective mast-cell stabilizer would go beyond the available clinical evidence.

Margaret's Clinical Observations

In my work with complex chronic illness, I have encountered women who report changes in flushing, headaches, food-related symptoms, or other histamine-associated complaints during hormonal transitions.

These patterns led me to consider whether changing progesterone and estrogen signaling might influence symptom variability in selected patients.

The observation is clinically interesting, even though it does not establish that progesterone treatment will improve every histamine-related condition.

Hormonal Symptoms vs. MCAS

Mast Cell Activation Syndrome is a specific clinical diagnosis requiring appropriate evaluation.

Hormonal fluctuations alone do not establish MCAS.

Similarly, not every headache, hot flash, or food intolerance indicates mast-cell disease.

A practitioner should examine the full clinical history and relevant diagnostic criteria.

10. COVID, Post-Viral Illness, and Hormonal Changes

COVID-19 and other significant illnesses can affect multiple physiological systems.

Researchers have examined menstrual changes, endocrine findings, inflammatory responses, and persistent symptoms following infection.

Menstrual and Hormonal Changes After Illness

Some women report changes in menstrual timing, bleeding patterns, or symptoms following significant illness.

Multiple factors may contribute, including fever, systemic inflammation, changes in weight, stress, and temporary alterations in reproductive hormone signaling.

Margaret's Clinical Experience

During the COVID era, I observed patients presenting with unusual menstrual or postmenopausal bleeding concerns.

Some had histories involving recent infection, vaccination, or other significant health events.

Those temporal associations deserve to be documented and investigated, but they do not independently establish the cause of the bleeding.

In particular, postmenopausal bleeding always warrants appropriate medical evaluation, regardless of whether it occurred after infection, vaccination, or a change in hormone therapy.

Questions About Spike Protein and Reproductive Tissues

Researchers continue investigating the biological effects of SARS-CoV-2 infection, viral proteins, and immune responses in different tissues.

Specific claims that persistent spike protein universally accumulates in reproductive organs or explains a broad pattern of hormonal disorders require careful source-specific evaluation.

Observations from particular studies cannot automatically be generalized to everyone with long COVID or everyone who received a COVID vaccine.

Does Progesterone Treat Long COVID?

Progesterone's neuroactive metabolites and immune-related effects have generated interest in possible applications beyond routine reproductive care.

However, bioidentical progesterone is not an established treatment for long COVID.

Patients with post-viral symptoms deserve an individualized assessment of reproductive, thyroid, neurological, sleep, and other possible contributors.

11. Oral vs. Topical Bioidentical Progesterone

The route by which a hormone enters the body affects its absorption, metabolism, and clinical behavior.

Oral Micronized Progesterone

Oral micronized progesterone is absorbed through the gastrointestinal tract and undergoes substantial first-pass metabolism.

This produces neuroactive metabolites, including allopregnanolone-related compounds.

Sedation or dizziness can occur.

Oral micronized progesterone is available as an FDA-approved prescription product for specific indications.

Topical Progesterone

Topical progesterone preparations are applied to the skin.

Their absorption and resulting hormone concentrations may vary according to formulation and other factors.

Many topical creams are compounded or marketed outside the standards used for FDA-approved systemic hormone products.

Can Topical Progesterone Protect the Uterus?

This is an especially important clinical distinction.

Topical progesterone creams should not be assumed to provide adequate endometrial protection for women taking systemic estrogen.

Evidence for reliable endometrial protection is much stronger for appropriately prescribed and studied progestogen regimens.

Why Margaret Has Used Different Formulations

My functional medicine approach has included consideration of oral and transdermal hormone delivery based on the individual's symptoms, medical history, and treatment goals.

I pay attention to the differences in metabolism and tolerability.

However, a patient's treatment must be selected according to clinical evidence, appropriate indications, and safety considerations—not simply a preference for one route.

12. FDA-Approved vs. Compounded Bioidentical Hormones

One of the most common misunderstandings is that bioidentical hormones must be compounded.

They do not.

There are commercially manufactured, FDA-approved hormone products that are bioidentical.

FDA-Approved Products

FDA-approved medicines undergo review for specified indications, quality, manufacturing standards, and labeling.

Oral micronized progesterone is one example.

Its labeling includes indications, contraindications, and warnings relevant to safe prescribing.

Compounded Products

Compounded medications may be appropriate when a patient has a specific need that cannot be met by an available commercial product—for example, certain ingredient allergies.

However, compounded formulations generally do not undergo the same premarket FDA review as approved products.

Their potency, absorption, and evidence base may differ.

What Patients Should Ask

Before choosing a hormone preparation, ask:

• Is it FDA-approved or compounded?
• What is the exact hormone and route of administration?
• What clinical indication is being treated?
• What evidence supports that formulation?
• What side effects or contraindications are relevant?
• If estrogen is being prescribed, how will the endometrium be protected?
• What follow-up is recommended?

The Menopause Society and ACOG generally favor approved hormone products over routine use of custom-compounded menopausal hormones when suitable approved options exist.

13. Safety Considerations Before Using Progesterone

Hormones are biologically active medications and should be used with appropriate medical oversight.

Unexplained Vaginal Bleeding

Unexpected or unexplained vaginal bleeding requires evaluation.

Postmenopausal bleeding is particularly important because it may indicate endometrial pathology.

Do not begin hormone treatment in an attempt to suppress unexplained bleeding without determining its cause.

History of Cancer

A history of breast cancer or another hormone-sensitive condition may influence whether hormone therapy is appropriate.

The decision requires individualized specialist guidance.

Thromboembolic and Cardiovascular Conditions

The risks of hormone therapy vary with the medication, route, combination, and patient history.

A history of blood clots, stroke, or other relevant cardiovascular disease may be a contraindication to particular treatments.

Liver Disease

Significant liver disease can affect medication metabolism and treatment suitability.

Changing from oral to topical hormone administration does not automatically make therapy safe.

Medication Interactions and Sedation

Oral progesterone may cause sedation or dizziness.

Other medications, alcohol use, and individual factors may influence tolerability.

Ingredient Allergies

Some progesterone capsule formulations contain peanut oil.

Patients with allergies must check the specific product ingredients.

Why Hormone Monitoring Should Be Individualized

Laboratory testing can be useful for diagnosing selected endocrine conditions.

However, complex saliva or dried-urine hormone panels are not universally validated for choosing or adjusting menopausal hormone regimens.

Treatment should be monitored according to the actual clinical indication and appropriate medical guidance.

14. Questions to Ask Your Hormone Healthcare Professional

1. Are my symptoms consistent with a hormonal transition, or should other causes be investigated?
2. Would progesterone be appropriate for my situation?
3. What is the difference between progesterone and synthetic progestins?
4. Is the proposed product FDA-approved?
5. How does oral administration differ from topical or vaginal administration?
6. Could the medication affect sleepiness, mood, or dizziness?
7. Do I have any contraindications?
8. If I am using estrogen and have a uterus, how will my endometrium be protected?
9. Are any abnormal bleeding patterns concerning?
10. How will we determine whether treatment is helping?
11. What side effects would require reassessment?
12. Are nonhormonal options appropriate for my symptoms?

Frequently Asked Questions

Is bioidentical progesterone the same as a synthetic progestin?

No. Bioidentical progesterone has the same molecular structure as endogenous progesterone. Synthetic progestins are structurally modified compounds with potentially different receptor and metabolic effects.

Can progesterone help with sleep?

Some studies and clinical observations suggest oral micronized progesterone may improve selected sleep outcomes in certain women.

It is not appropriate for everyone, and persistent insomnia may require evaluation for sleep apnea or other causes.

Why does oral progesterone sometimes cause sleepiness?

First-pass metabolism produces neuroactive steroid metabolites that influence GABA-A receptor signaling.

Is bioidentical progesterone safer than all synthetic progestins?

Risks and benefits differ among specific products, doses, routes, and patient populations.

Bioidentical progesterone should not be described as universally risk-free or superior for every outcome.

Does progesterone prevent breast cancer or brain tumors?

Progesterone is not an established preventive treatment for either condition.

Research involving hormone formulations and cancer risks must distinguish specific drugs, exposure patterns, and outcomes.

Patients with relevant personal histories should discuss therapy with qualified specialists.

Can topical progesterone creams protect the uterine lining?

Topical creams should not be assumed to provide reliable protection when systemic estrogen is used.

Appropriately validated treatment is essential.

Can progesterone stabilize mast cells?

Laboratory and clinical observations suggest interactions between progesterone signaling and immune activity.

However, progesterone is not an established stand-alone treatment for MCAS.

Can men use progesterone?

Men naturally produce progesterone, but prescribing progesterone to treat symptoms such as abdominal weight gain or presumed estrogen dominance is not an established routine therapy.

Potential risks and endocrine effects require specialist evaluation.

Does progesterone treat long COVID?

No established clinical evidence supports progesterone as a standard treatment for long COVID.

Research into neurosteroids and post-viral biology remains of interest.

Should all women have comprehensive hormone testing?

No. Testing should be selected according to symptoms, medical history, and the clinical decision being considered.

What if I have bleeding after menopause?

Seek medical evaluation. Even when bleeding occurs after a change in medication, infection, or vaccination, the cause must be properly investigated.

Final Thoughts: Understanding the Whole Hormonal Picture

Progesterone participates in far more than reproduction.

Its metabolic pathways connect steroid hormone production with the nervous system, and its downstream metabolites interact with important neurotransmitter receptors.

During perimenopause and other hormonal transitions, changes in progesterone production may contribute to symptoms that extend beyond menstruation.

My clinical experience has also led me to investigate possible relationships involving sleep, stress physiology, environmental exposures, histamine-related symptoms, and immune regulation.

These relationships are complex.

Not every symptom indicates a progesterone deficiency, and not every proposed mechanism has been demonstrated as a clinical treatment pathway.

Nevertheless, understanding progesterone physiology can help women ask better questions and participate more meaningfully in decisions about their health.

My goal is to help women understand the connections among their hormones, nervous system, environment, and overall well-being—while choosing treatment based on their individual needs.

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About the Author

Dr. Margaret Christensen, MD, is a board-certified obstetrician-gynecologist and functional medicine physician whose work has included women's health, hormone-related concerns, environmental medicine, and education.

Her approach emphasizes understanding physiological connections, considering the patient's history, and encouraging informed participation in healthcare decisions.

Educational Disclaimer

This article presents educational information about progesterone physiology, hormone therapy, and Dr. Christensen's clinical observations.

Some proposed mechanisms and clinical interpretations are emerging and have not been established as treatments for specific illnesses.

The material does not constitute individualized hormone therapy advice. Prescription hormones require appropriate medical evaluation, and readers should not independently start, stop, or change hormonal medications.

Sources and Further Reading

• Dr. Margaret Christensen. Hormonal Havoc educational materials and COVID Fallout presentations, 2024.
• Dr. Margaret Christensen and colleagues. Toxic Mold Summit and associated educational discussions.
• American College of Obstetricians and Gynecologists. Compounded Bioidentical Menopausal Hormone Therapy. Clinical Consensus No. 6, 2023.
• The Menopause Society. Hormone Therapy patient education and position statements.
• U.S. Food and Drug Administration. Progesterone Capsules Prescribing Information.
• The North American Menopause Society. The 2022 Hormone Therapy Position Statement.