Overview
This page covers hormone replacement therapy as a family of medical treatments: menopausal estrogen with or without progestogen, low-dose vaginal estrogen, testosterone therapy in men and in women, and compounded preparations marketed as bioidentical. It explains how the names are used, how the members differ, and what guidelines, trials and professional-society statements report about benefits and risks, keeping the evidence for each member separate. It is information only and gives no dosing or regimens.
What types of Hormone Replacement Therapy are there?
| Type | How it differs |
|---|---|
| Menopausal estrogen-progestogen therapy | Combines estrogen with a progestogen, used in women with a uterus; the Women's Health Initiative tested one such combination. |
| Menopausal estrogen-alone therapy | Uses estrogen without a progestogen, studied in women who had a hysterectomy; its trial and breast cancer findings differ from the combined form. |
| Low-dose vaginal estrogen | Applied locally for genitourinary symptoms of menopause; the largest breast cancer analysis reported its risk separately from systemic estrogen. |
| Testosterone replacement therapy in men | Addresses symptomatic testosterone deficiency in men; its main safety questions concern cardiovascular events, the prostate and hematocrit. |
| Testosterone therapy in women | A position statement limits it to confirmed hypoactive sexual desire disorder after menopause and describes it as off-label. |
| Compounded 'bioidentical' hormone therapy | Custom-prepared hormone products marketed as bioidentical or natural; a National Academies review found limited evidence for their claims. |
| Hormone Pellet Therapy | Small testosterone or estradiol pellets implanted under the skin; compounded versions lack the trial data of licensed products. |
| DHEA Supplementation | An adrenal hormone precursor sold as a supplement, and as a licensed vaginal product for menopausal symptoms. |
| Human Growth Hormone Anti-Aging | Growth hormone used off-label for ageing or performance; reviews in healthy older adults found side effects and little benefit. |
Where does Hormone Replacement Therapy come from?
Early estrogen products and shifting use
A historical review reports that the US Food and Drug Administration approved marketing of diethylstilbestrol in 1941 and conjugated equine estrogens in 1942 for menopausal symptoms. Estrogen sales doubled and tripled from the mid-1960s to 1975, when reports of increased endometrial cancer in estrogen users led to a sharp decline. Use rose again after evidence that progestins protect against estrogen-induced endometrial changes, a 1982 bone-mass report and a 1984 National Institutes of Health consensus statement on bone loss. Observational reports of lower coronary heart disease among users also encouraged use through the 1990s, and by 2001 about 15 million US women were using estrogen with or without a progestin.
The Women's Health Initiative and its aftermath
The same review states that the 2002 Women's Health Initiative report of greater harm than benefit from combined conjugated equine estrogens and a progestin produced a sharp fall in use and a serious reevaluation of menopausal hormone therapy, along with interest in alternatives such as 'bioidentical' hormones. A later review adds that sales also dropped after the 2003 Million Women Study, and that breast cancer incidence fell by up to 22 percent in many US and European populations between 2001-2002 and 2005-2006. Its authors judge the decline to be largely attributable to reduced hormone use, which is an ecological association and not a trial result.
Testosterone therapy in the sources reviewed
The sources reviewed for this page do not give a dated origin story for testosterone therapy. The Endocrine Society's 2018 guideline states that it updates a 2010 guideline on androgen deficiency syndromes in men. A 2025 Latin American position statement says androgens have been prescribed to relieve symptoms in midlife women but that no clearly established indications for testosterone therapy exist.
What do the names and terms mean?
Names used for the family
The sources reviewed use several overlapping names. Titles refer to hormone replacement therapy, menopausal hormone therapy, hormone therapy, testosterone-replacement therapy and testosterone therapy, and spell the progesterone-like component as progestin, progestagen or progestogen. This page uses hormone replacement therapy as an umbrella label only. The sources do not treat the members as one intervention, and the choice of name does not imply that findings for one member apply to another.
How 'bioidentical' is used
A National Academies report describes compounded preparations as often marketed as 'bioidentical' or 'natural'. The committee says the public often misreads the term, retains it only to identify these products without endorsing them, and notes that FDA has approved several bioidentical hormone products, so custom compounding is not the only source of such hormones. The Latin American statement places the word in quotation marks when it refers to compounded testosterone.
Why the members are kept separate
The North American Menopause Society states that the risks of hormone therapy differ by type, dose, duration, route of administration, timing of initiation and whether a progestogen is used. The Women's Health Initiative tested specific products, and the entries below therefore report each member's findings under that member's own heading and do not carry a result from one to another.
What does Hormone Replacement Therapy involve?
Estrogen with or without progestogen
In the Women's Health Initiative, women with a uterus received an estrogen-progestin combination or placebo, while women who had a hysterectomy received estrogen alone or placebo. The US Preventive Services Task Force likewise assesses the two forms separately. A historical review explains the reason for the split: progestins were added because they protect against estrogen-induced changes in the uterine lining. The Menopause Society statement also addresses low-dose vaginal estrogen, used for genitourinary symptoms in women who do not have indications for systemic therapy.
Testosterone therapy in men
The Endocrine Society guideline recommends diagnosing hypogonadism only in men with symptoms and signs of testosterone deficiency and unequivocally, consistently low serum testosterone, confirmed by repeat fasting morning measurement. It recommends therapy for symptomatic deficiency after discussing benefits and risks, and describes monitoring of symptoms, adverse effects, testosterone and hematocrit levels, and prostate cancer risk during the first year.
Compounded preparations
The National Academies report describes compounded hormone products as custom-prepared and not reviewed by FDA for safety, quality or effectiveness. It reports that oversight of formulation, testing and dispensing is limited and varies between states and pharmacies, and that compounded products need not carry the full labeling and package inserts of approved products, so ingredient lists and contraindications may be incomplete.
What is Hormone Replacement Therapy used for?
Menopausal symptoms and bone loss
The Menopause Society position statement describes hormone therapy as the most effective treatment for vasomotor symptoms and for the genitourinary syndrome of menopause, and states that it has been shown to prevent bone loss and fracture. The Women's Health Initiative trials found fewer hip fractures and fewer vasomotor symptoms with active treatment, and the 2002 report of the combined trial recorded fewer colorectal cancers.
Prevention of chronic disease
Chronic disease prevention was once a common reason for use, helped by observational reports of lower coronary heart disease. The Women's Health Initiative follow-up concluded that its findings do not support the therapy for chronic disease prevention. The US Preventive Services Task Force recommends against both combined estrogen-progestin and estrogen alone for primary prevention of chronic conditions in postmenopausal persons, with moderate certainty of no net benefit.
Testosterone and compounded products
For men, the Endocrine Society guideline names symptomatic testosterone deficiency as the indication. For women, a Latin American position statement limits testosterone to postmenopausal hypoactive sexual desire disorder and advises against systemic DHEA for sexual symptoms. A National Academies review of the evidence behind marketing claims for compounded bioidentical hormones found no support that they are safer or more effective than approved products.
What does the research show?
Women's Health Initiative: combined therapy
The 2002 report randomized 16,608 US women aged 50 to 79 with a uterus to conjugated equine estrogens plus medroxyprogesterone acetate or placebo. The trial stopped after a mean 5.2 years. Hazard ratios were 1.29 for coronary heart disease, 1.26 for invasive breast cancer, 1.41 for stroke and 2.13 for pulmonary embolism, with 0.66 for hip fracture and 0.63 for colorectal cancer. All-cause mortality was unchanged. Absolute excess per 10,000 person-years was 7 coronary events, 8 strokes, 8 pulmonary emboli and 8 breast cancers.
Women's Health Initiative: estrogen alone and follow-up
The 2013 integrated report followed 27,347 women, including 10,739 with prior hysterectomy randomized to conjugated equine estrogens alone or placebo. During estrogen-alone treatment the hazard ratio for coronary heart disease was 0.94 and for invasive breast cancer 0.79, with cumulative breast cancer HR 0.79 (0.65 to 0.97). For the combined trial, cumulative breast cancer HR was 1.28 (1.11 to 1.48). Neither regimen changed all-cause mortality, and both increased stroke and pulmonary embolism.
Breast cancer in observational data
A pooled analysis of 58 studies reported relative risks for current users after 5 to 14 years of 2.08 for estrogen plus progestagen and 1.33 for estrogen alone, with 1.09 (not statistically significant) for vaginal estrogens. Some excess persisted more than 10 years after stopping. Observational data cannot show causation, and screening may affect detection.
Timing of initiation
The Menopause Society judges the benefit-risk balance favorable for bothersome vasomotor symptoms in women under 60 or within 10 years of menopause without contraindications, and less favorable later because absolute risks of heart disease, stroke, venous thromboembolism and dementia are greater. In the Women's Health Initiative, estrogen-alone results were more favorable at ages 50 to 59 (nominal trend P below .05).
Testosterone in men and compounded products
TRAVERSE randomized 5,246 men aged 45 to 80 with symptoms, low testosterone and cardiovascular disease or high risk to testosterone gel or placebo. Major cardiovascular events occurred in 7.0 percent versus 7.3 percent (HR 0.96, 0.78 to 1.17), meeting noninferiority. A later review reports low prostate cancer rates in both groups, with a larger early PSA rise on testosterone. For compounded products, the National Academies committee found little high-quality data and no basis for definitive conclusions.
What are the safety considerations?
Estrogen-progestogen and estrogen-alone therapy
The Women's Health Initiative follow-up lists increased stroke, pulmonary embolism, gallbladder disease and urinary incontinence for both regimens, and dementia in women aged 65 and older receiving the combined regimen. The first estrogen-progestin report found an excess of 7 to 8 events per 10,000 person-years for each of coronary disease, stroke, pulmonary embolism and breast cancer. A historical review reports that estrogen used without a progestin raised endometrial cancer concerns in the 1970s. Estrogen alone was studied in women who had a hysterectomy.
Testosterone in men
The Endocrine Society guideline recommends against starting testosterone therapy in men planning near-term fertility or with breast or prostate cancer, a palpable prostate nodule, elevated PSA or elevated hematocrit, untreated severe sleep apnea, uncontrolled heart failure, recent myocardial infarction or stroke, or thrombophilia. In TRAVERSE, atrial fibrillation, acute kidney injury and pulmonary embolism were more frequent with testosterone. The sources reviewed give hematocrit a monitoring role but do not quantify erythrocytosis rates.
Testosterone in women and compounded products
The Latin American statement does not recommend subcutaneous pellets or compounded 'bioidentical' testosterone, citing risks of supraphysiological dosing and insufficient evidence, and requires patients to be told that testosterone use in women is off-label. The National Academies report warns that absence of evidence of harm is not evidence of absence of harm, and cites variable potency and incomplete labeling as quality concerns.
Care boundaries and gaps in the sources
These treatments are prescription medical care. The Menopause Society calls for individualized treatment with periodic reevaluation, and the Endocrine Society calls for discussing benefits and risks before testosterone therapy. This page does not replace that care, and it should not be used to delay or replace necessary medical care. The sources reviewed do not address practitioner training or registration, and no statute or regulatory material was reviewed.
Connected Entries
Showing 8 of 10 related records.
Classification and context
- Entry type
- Modality
- Practice type
- Prescription hormone treatments (menopausal and androgen therapy)
- Traditions
- Gynecology, Endocrinology, Menopause medicine
- Concepts
- Estrogen, Progestogen, Testosterone, Vasomotor symptoms, Genitourinary syndrome of menopause, Hypogonadism, Compounded preparations, Bioidentical, Timing of initiation, Shared decision-making
- Categories
- Complementary
Sources and discovery context
Research and public-health sources support evidence and safety context. Directory and discovery sources describe navigation, relationships, practitioners, and access—not clinical efficacy.
Randomized trial that was stopped early after a mean 5.2 years, reporting hazard ratios for heart disease, breast cancer, stroke and other outcomes.
How this source relates
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- Exact source page
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- Supports results for one estrogen-progestin combination in healthy US women aged 50-79 with a uterus; must not be applied to estrogen alone, other products, testosterone or compounded hormones.
- Supports sections
- Terminology, Claimed Uses, Research and Evidence, Safety and Suitability
Reports intervention and cumulative follow-up outcomes through 13 years for 27,347 women in two trials.
How this source relates
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- Exact source page
- Relationship
- Supports separate findings for estrogen plus progestin and for estrogen alone in the WHI populations; must not be generalized to other preparations or to testosterone.
- Supports sections
- Terminology, Practice Description, Claimed Uses, Research and Evidence, Safety and Suitability
Pooled 58 studies and reported relative risks by hormone type, duration and time since stopping.
How this source relates
- Source link
- Exact source page
- Relationship
- Supports observational breast cancer associations for systemic estrogen-progestagen, estrogen-only and vaginal estrogen; says nothing about testosterone or compounded products and does not establish causation.
- Supports sections
- Research and Evidence
States that risks vary by type, dose, duration, route, timing and progestogen use, and that treatment should be individualized.
How this source relates
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- Exact source page
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- Supports the society's summary of menopausal hormone therapy benefits, risks and timing; does not cover testosterone in men.
- Supports sections
- Terminology, Practice Description, Claimed Uses, Research and Evidence, Safety and Suitability
Recommends against combined estrogen-progestin and against estrogen alone for primary prevention of chronic conditions.
How this source relates
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- Exact source page
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- Applies to systemic hormone therapy for primary prevention in asymptomatic postmenopausal persons; it is not a statement about treating menopausal symptoms.
- Supports sections
- Practice Description, Claimed Uses
Traces approvals, changing use, and the effect of the 2002 trial report on prescribing.
How this source relates
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- Exact source page
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- Supports the US timeline of estrogen products and use through 2005; does not cover testosterone.
- Supports sections
- History and Origins, Practice Description, Claimed Uses, Safety and Suitability
Reviews population breast cancer incidence changes after hormone use declined from 2002.
How this source relates
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- Exact source page
- Relationship
- Supports the timing of falling use and breast cancer incidence; the link is ecological and does not prove causation.
- Supports sections
- History and Origins
Sets diagnostic requirements, conditions against starting therapy and a monitoring plan.
How this source relates
- Source link
- Exact source page
- Relationship
- Applies to men with hypogonadism; does not apply to women or to estrogen-based therapy.
- Supports sections
- History and Origins, Terminology, Practice Description, Claimed Uses, Safety and Suitability
Reports noninferiority for major cardiovascular events and more atrial fibrillation, kidney injury and pulmonary embolism with testosterone.
How this source relates
- Source link
- Exact source page
- Relationship
- Applies to one transdermal product in men aged 45-80 with symptoms and cardiovascular disease or risk; must not be applied to women, other products or compounded testosterone.
- Supports sections
- Terminology, Research and Evidence, Safety and Suitability
Summarizes prostate safety data from randomized trials including TRAVERSE.
How this source relates
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- Applies to screened men with hypogonadism in four randomized trials; not to men at high prostate cancer risk, women or other members.
- Supports sections
- Research and Evidence
Limits testosterone to confirmed hypoactive sexual desire disorder and does not recommend pellets or compounded testosterone.
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- Exact source page
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- Applies to testosterone and DHEA in midlife and older women; must not be used for men or for estrogen therapy.
- Supports sections
- History and Origins, Terminology, Claimed Uses, Safety and Suitability
Finds little high-quality data on compounded products and no support for claims of superiority.
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- Exact source page
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- Applies to compounded bioidentical products; says nothing about the efficacy of approved estrogen or testosterone products.
- Supports sections
- Terminology, Practice Description, Claimed Uses, Research and Evidence, Safety and Suitability
Links to Gyfts Hormone Replacement Therapy page for this practice, for discovery only. The platform's descriptions and claims are not independent claims. Machipedia does not rely on them for evidence.
How this source relates
- Source link
- Exact source page
- Relationship
- Links to Gyfts' page for this practice, for discovery only. The platform's descriptions and claims are not independent evidence, and nothing on this Machipedia page relies on them.
- Supports sections
- Practice Description