Bioidentical hormones are hormones that are created synthetically in a laboratory and are designed to have a chemical structure that is identical tohormones in the human body. There is significant confusion both in the lay and professional community regarding bioidentical hormones, what they are, what they are not and understanding their safety profile.
Bioidentical hormones
Are not necessarily natural or botanical
May or may not be created in a compounding pharmacy
May also be created in an FDA approved laboratory
Are not necessarily “healthy” nor “safe”
Bioidentical hormones which are FDA-approved and regulated, may be safer than ones created in a compounding pharmacy as those may be subject to human error and are not subject to the rigorous standards and regulations of the FDA
Many prescription hormones are bioidentical
Drug companies often develop non-bioidentical hormones because they can then be patented, while bioidentical ones cannot
When hormones are bioidentical the only way the drug company can patent them is by creating a new or different “delivery system”
For example, drug delivery by a “patch” or use of a different compound to deliver the drug
‘Regulated body-identical hormone therapy (rBHT)’ is a term that is used by some to help differentiate between regulated from unregulated forms of bioidentical hormones
ACOG states
Clinicians should counsel patients that FDA-approved menopausal hormone therapies are recommended for the management of menopausal symptoms over compounded bioidentical menopausal hormone therapy
Genitourinary Syndrome of Menopause: New Name, Old Problem
Previously known as atrophic vaginitis, vulvovaginal atrophy (VVA), or urogenital atrophy, genitourinary syndrome of menopause (GSM) is a composite of genital, urologic and sexual sequelae of chronic hypoestrogenism. Sexual dysfunction and quality of life impairment are important to identify, as treatment options are available. Incidence is unknown as the syndrome is often underreported by women due to embarrassment, disregard, or a sense of inevitability.
KEY POINTS:
Risk Factors
Lactation
Hyperprolactinemia
Autoimmune disorders
Bilateral oophorectomy
Pelvic radiation
Chemotherapy
Medications including
GnRH agonists (leuprolide, nafarelin)
SERMs (such as tamoxifen)
Aromatase inhibitors,
Danazol
Progestins
Lifestyle risk factors including
Cigarette smoking, Alcohol abuse | Sexual abstinence | Lack of exercise | Lack of vaginal birth
The Menopause Society (previously NAMS) position statement on hormone therapy is based on an extensive literature review. Hormone therapy (HT) is the most effective treatment for vasomotor symptoms (VMS; hot flashes, night sweats) and genitourinary syndrome of menopause (GSM). The statement has been endorsed by over 20 international organizations.
Prior estrogen sensitive cancer (including breast cancer)
Prior coronary heart disease
Stroke, MI or VTE
Personal history/inherited high risk of thromboembolic disease
POTENTIAL RISKS OF HT
Women <60 Years or Who are Within 10 Years of Menopause
Breast cancer (rare risk) with combined estrogen-progestogen therapy
Endometrial hyperplasia and cancer with unopposed estrogen
VTE
Biliary issues
FDA APPROVED INDICATIONS FOR HT
Bothersome vasomotor symptoms
Prevention of bone loss
Hypoestrogenism caused by hypogonadism, surgical castration or premature ovarian insufficiency
Genitourinary symptoms
NAMS RECOMMENDATIONS FOR TYPE / REGIMEN / DURATION OF USE
Individualize Type, Dose & Regimen
For women with a uterus and using systematic estrogen, ensure endometrial protection (Level I)
Use adequate dose and duration of a progestogen
In WHI, addition of medroxyprogesterone acetate 2.5 mg daily resulted in same risk of endometrial cancer as placebo (hazard ratio 0.81 (95% CI 0.48-1.36)
combine conjugated equine estrogens (CEE) with bazedoxifene
Progestogen therapy not recommended for low-dose vaginal estrogen therapy (ET)
Evaluate endometrium if bleeding does occur
Avoid compounded bioidentical HT given concerns about safety
Do not use salivary hormone testing to dictate dosing
Individualize Duration
Premature menopause, either natural or induced <45 years and especially if <40 years
Continue HT at least until age 52, which is the median age of menopause (Level II)
The recommendation to routinely discontinue HT in women aged 65 and older is not supported by data
Decision to continue >60 years of age includes quality of life, VMS, bone loss/fracture and other medical risks vs benefits
NAMS RECOMMENDATIONS FOR SPECIAL POPULATIONS AND CANCER RISK
Family History of Breast Cancer or BRCA Positive Following Prophylactic Oophorectomy
Use of HT does not appear to increase the relative risk for breast cancer
Family history is a risk factor for breast cancer and should be assessed when counseling about HT
Ovarian Cancer
Recent and current use of hormone therapy is associated with a small increase in serous type of ovarian cancer
One additional ovarian cancer death in 1,700 to 3,300 HT users
Both combined estrogen-progestogen therapy and ET
Risk dissipates within 5 years of discontinuing HT
After diagnosis of epithelial ovarian cancer, HT does not affect recurrence risk or survival
Benefits of use outweigh risks
Not recommended in hormone-dependent ovarian cancers (granulosa-cell tumors and low-grade serous carcinoma)
Breast and Endometrial Cancer Survivors: Systemic HT for VMS
Encourage nonhormonal therapies
Endometrial cancer survivor
If VMS not well controlled, may consider HT in conjunction with oncologist
Breast cancer survivor (especially ER+)
Systemic HT should not be offered but if other nonhormonal alternatives have failed, shared decision making that includes an oncologist can be considered
Breast and Endometrial Cancer Survivors: Low-dose Vaginal ET
Low-dose vaginal ET has minimal systematic absorption and appears to hold minimal to no risk for breast or endometrial cancer
Endometrial cancer survivor following hysterectomy and successful treatment
Consider low-dose vaginal ET in nonhormonal options are unsuccessful
Breast cancer survivors
Decisions regarding low-dose vaginal estrogen should involve the treating oncologist especially if patient is on aromatase inhibitors
Colorectal Cancer
Overall decreased risk of colorectal cancer in current HT users compared to non-users
No benefit associated with prior use
Lung Cancer
No effect on lung cancer incidence and/or survival
HORMONAL THERAPY DOSAGE/REGIMENS
NOTE: For women with a uterus and using systematic estrogen, ensure endometrial protection with an adequate dose of a progestogen
VSM: Systemic
Standard Dose
Conjugated estrogen 0.625 mg/d
Micronized estradiol-17β 1 mg/d
Transdermal estradiol-17β 0.0375–0.05 mg/d
Low Dose
Conjugated estrogen 0.3–0.45 mg/d
Micronized estradiol-17β 0.5 mg/d
Transdermal estradiol-17β 0.025 mg/d
CEE + SERM
Conjugated estrogen 0.45 mg/d and bazedoxifene 20 mg/d
19-nortestosterone derivative synthetic steroid
Tibolone 2.5 mg/d
Note: Progestin-only medications, testosterone, or compounded bioidentical hormones for the treatment of vasomotor symptoms are not recommended
GSM: Systemic
Standard Dose
Conjugated estrogen 0.625 mg/d
Micronized estradiol-17β 1 mg/d
Transdermal estradiol-17β 0.0375–0.05 mg/d
Low Dose
Conjugated estrogen 0.3–0.45 mg/d
Micronized estradiol-17β 0.5 mg/d
Transdermal estradiol-17β 0.025 mg/d
PROGESTOGENS FOR UTERINE PROTECTION – when using standard dose estrogen
Medroxyprogesterone acetate
2.5 mg po daily for continuous therapy
5 mg daily po with sequential therapy for 12 – 14 days sequentially per 28-day cycle (start day 1 or 16)
Micronized progesterone
100 mg po daily for continuous therapy
200 mg po nightly for 12 days sequentially per 28-day cycle
Formulated with peanut oil – do not use in women with peanut allergies
May cause hypnotic effects and should be taken at bedtime
GSM: Local (vaginal, and in the case of creams may also be applied to vestibular area)
Estradiol-17β ring (releases 7.5 micrograms/d): replace every 3 months
Estradiol vaginal tablet (10 micrograms/d): place nightly for 2 weeks
Maintenance is one tablet 2 times/week
Note: this is the corrected dose in ACOG PB 141
Estradiol-17β cream (0.1 mg active ingredient/g): 2-4 g/d for 1 to 2 weeks
Gradually reduce to ½ initial dosage for 1 – 2 weeks
Maintenance is 1 g, 1 to 3 times/week
Conjugated estrogen cream (0.625 mg/g): 0.5–2 g/d for 21 days then off for 7 days
In practice during maintenance therapy, most women apply 1 – 3 times /week
KEY POINTS:
Risks of HT differ depending on type/dose/duration/route/timing of initiation and whether a progestogen is needed
Individualize treatment to maximize benefits/minimize risk
Reassess periodically
Women younger than 60 or within 10 years of menopause without contraindications have a favorable benefit-risk ratio for use of HT in the treatment of VMS and reducing bone loss/fracture for those at increased risk
Longer duration may be more favorable for estrogen therapy alone vs combined estrogen-progestin therapy based on the WHI RCTs
Women who begin HT more than 10 years from menopause onset or aged 60 or older have a less favorable benefit-risk ratio, with greater absolute risks of CHD, stroke, thrombosis and dementia
Low-dose vaginal estrogen therapy is recommended for GSM symptoms not relieved with other therapies
Nonestrogen therapies like ospemifene and intravaginal DHA are approved for use in postmenopausal women
Cognition
HT is not recommended to prevent cognitive decline
Starting HT >65 years has been associated with increased risk for dementia | Normal cognition prior to initiation may attenuate this effect
ET may have cognitive benefits if started immediately following hysterectomy with bilateral oophorectomy
HT in the early natural postmenopause period does not appear to impact cognitive function
The USPSTF Guidance on the Role of Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Persons
The USPSTF assessed the evidence for harms and benefits for chronic disorders such as coronary heart disease, dementia, stroke, fractures, and breast cancer
The USPSTF concludes with moderate certainty that there is no net benefit in the use of hormone therapy
The USPSTF recommends against the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal persons (*D recommendation)
The USPSTF recommends against the use of estrogen alone for the primary prevention of chronic conditions in postmenopausal persons who have had a hysterectomy (*D recommendation)
*D recommendation Suggestion for Practice: Discourage the Use of This Service
FDA Removal of Black Box Warning
On November 10, 2025, the FDA initiated removal of the ‘Black Box’ warning on hormone therapy labelling “to provide current, accurate and balanced information about the benefits and risks of these drugs, so women, in consultation with their healthcare providers, can make the best decisions for their health”
FDA label recommendation for start date: Within 10 years of menopause onset or before 60 years of age for systemic hormone therapy
However, starting time and duration “are decisions made between the prescriber and the individual patient”
All references to risks of cardiovascular disease, breast cancer, and probable dementia will no longer appear
The FDA states that there is literature to support risk reduction for the following
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This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. The planners of this activity do not recommend the use of any agent outside of the labeled indications.
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presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications and/or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.
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