Estradiol + progesterone
Estradiol + progesterone has been studied in 16 papers since 2001: 3 trials and 1 observational study in people, 7 in animals, 3 reviews; 6 in the past year. It is an approved medicine. The newest paper, Sep 29, 2026: “Bone Mineral Density in Women with Functional Hypothalamic Amenorrhea: A Systematic Review and Meta-Analysis”.
16 papers study it221 more mention it13 findingsUpdated
10 new papers in 30 daysSee all 237
“Kaplan-Meier analyses showed no significant differences in fracture recurrence and mortality between the two groups.”
None of its findings points the other way.
- 6 independent labs in 4 countries
- 26 trials, 2 about aging, 8 with no results posted
- Funders: National Institute on Aging and others
- 2 of 10 findings with company ties
- Human trial3
- Humans1
- Animals7
- In silico1
Studies in people
2 studies gave estradiol + progesterone to people and measured what changed.
no change: Has no effect on recurrent fracture8.63 vs 12.86 per 100 PY, p = 0.180
no change: Has no effect on mortality3.58 vs 4.40 per 100 PY, p = 0.503
up: Increases bone mineral density+2.8%
Randomized trial281 peopleWomen4 years
Postmenopausal women; recent hip fracture
Climacteric : the journal of the International Menopause Society, Jul 4, 2021
up: Increases skin surface lipids
Trial24 peopleWomen45-68 years6 months
Midlife adults; Postmenopausal women
Maturitas, Jul 25, 2001
What did studies of Estradiol + progesterone find?
12Studies of Estradiol + progesterone measured 12 outcomes; the most studied are mortality (2 studies), cartilage degeneration (2) and Cost-effectiveness (1).
Mortality
no changein humans1downin silico1
2 studies
Mortality
no changein humans1downin silico1
Estradiol + progesterone showed no clear effect on mortality in humans (recent hip fracture) (3.58 vs 4.40 per 100 PY, p = 0.503).
“The respective incidence of death per 100 PY was 3.58 and 4.40 (p = 0.503).”
Human trialrecent hip fracture1.5 mg/day estradiol gel + 100 mg/day oral micronized progesterone vs 35 mg/week risedronate4 yearsfemalesn = 281
Climacteric : the journal of the International Menopause Society
Estradiol + progesterone decreases mortality in silico with a uterus, 5 years use (-615 deaths per 10,000).
“was associated with 285 fewer cases of ASCVD, 18 more colon cancer cases, 46 more breast cancer cases, 183 fewer hip fractures, and 615 fewer deaths.”
In silicowith a uterus, 5 years usetransdermal E2 in combination with micronized progesterone5 yearsfemalesn = 10,000
Cost-Effectiveness Analysis of Menopausal Hormone Therapy
Obstetrics and gynecology
Cartilage degeneration
upin silico1downin mice1
2 studies
Cartilage degeneration
upin silico1downin mice1
Estradiol + progesterone protects against cartilage degeneration in mice (menopausal mice).
“restoration of 17β-estradiol and progesterone in menopausal mice protected against cartilage degeneration compared to untreated menopausal controls”
Animalsmenopausal micecartilagefemales
Nature aging
Estradiol + progesterone improves cartilage degeneration in silico cartilage network model of menopause.
“The greatest restoration was observed with combined estradiol/progesterone treatment (i.e., hormone therapy)”
In silicoin silico cartilage network model of menopause
A network medicine approach to elucidate mechanisms underlying menopause-induced knee osteoarthritis
bioRxiv (Cold Spring Harbor Laboratory)Preprint
Cost-effectiveness
upin silico1
1 study
Cost-effectiveness
upin silico1
Estradiol + progesterone improves cost-effectiveness in silico (hypothetical patients with a uterus, 5 years use) (-$127,738,990, +33,083 QALYs per 10,000).
“Micronized progesterone compared with no MHT was $127,738,990 less expensive, resulted in a gain of 33,083 QALYs”
In silicohypothetical patients with a uterus, 5 years usetransdermal E2 in combination with micronized progesterone5 yearsfemalesn = 10,000
Cost-Effectiveness Analysis of Menopausal Hormone Therapy
Obstetrics and gynecology
Obstructive sleep apnea
downin humans1
1 study
Obstructive sleep apnea
downin humans1
Estradiol + progesterone is linked with lower obstructive sleep apnea in humans (OSA).
“It is their synergistic action of progesterone and oestrogen which is responsible for the definitive improvement in patients with symptoms of OSA”
HumansOSAfemales
A Prospective Study on Effect of Reproductive Hormones on Obstructive Sleep Apnoea in Women
Bengal Journal of Otolaryngology and Head Neck Surgery
FOSB
upin mouse cells1
1 study
FOSB
upin mouse cells1
Estradiol + progesterone increases FOSB in vitro co-treatment.
“In vitro co-treatment with estradiol and progesterone increased FOSB and BACE1 levels, supporting the presence of a hormone-responsive regulatory link.”
Cellsin vitro co-treatment
Immunity & ageing : I & A
Behavioral function
upin rats1
1 study
Behavioral function
upin rats1
Estradiol + progesterone improves behavioral function in rats after ovariectomy.
“E2/P4 treatment rescued the OVX-induced compromise in neurogenesis and behavior at 9 months”
Animalsafter ovariectomyfemales
Stem cell reports
neurogenesis
upin rats1
1 study
neurogenesis
upin rats1
Estradiol + progesterone increases neurogenesis in rats after ovariectomy.
“E2/P4 treatment rescued the OVX-induced compromise in neurogenesis and behavior at 9 months”
Animalsafter ovariectomyfemales
Stem cell reports
Senescence markers
downin human cells1
1 study
Senescence markers
downin human cells1
Estradiol + progesterone decreases senescence markers in human cells (post-menopausal human chondrocytes).
“post-menopausal human chondrocytes displayed decreased markers of senescence and increased markers of chondrogenicity when cultured with 17β-estradiol and progesterone”
Cellspost-menopausal human chondrocytescartilage
Nature aging
Bone mineral density
upin humans1+2.8%
1 study
Bone mineral density
upin humans1+2.8%
Estradiol + progesterone increases bone mineral density in humans (recent hip fracture) (+2.8%).
“BMD at the total hip did not change in the risedronate group, but increased significantly by 2.8% in the MHT group.”
Human trialrecent hip fracturehip1.5 mg/day percutaneous estradiol gel plus oral micronized progesterone 100 mg/day4 yearsfemales
Climacteric : the journal of the International Menopause Society
Recurrent fracture
no changein humans1
1 study
Recurrent fracture
no changein humans1
Estradiol + progesterone showed no clear effect on recurrent fracture in humans (recent hip fracture) (8.63 vs 12.86 per 100 PY, p = 0.180).
“Kaplan-Meier analyses showed no significant differences in fracture recurrence and mortality between the two groups.”
Human trialrecent hip fracture1.5 mg/day estradiol gel + 100 mg/day oral micronized progesterone vs 35 mg/week risedronate4 yearsfemalesn = 281
Climacteric : the journal of the International Menopause Society
Skin surface lipids
upin humans1
1 study
Skin surface lipids
upin humans1
Estradiol + progesterone increases skin surface lipids in humans (combined estradiol and progesterone regimen).
“Skin surface lipids were increased during combined HRT”
Human trialcombined estradiol and progesterone regimenskinfemales
The influence of hormone replacement therapy on skin ageing: a pilot study
Maturitas
All 12Fewer
Has Estradiol + progesterone been tested in people?
2 about aging, of 26Yes: 3 trials and 1 observational study in people have been published, and 26 trials are registered.
About aging
Approved
Oct 28, 2018
Every condition in trials
Phase 4Results posted5 trials
Phase 4Completed2 trials
Phase 4Results posted2 trials
Phase 4Results posted2 trials
Phase 4Status unknown1 trial
Phase 4Status unknown1 trial
All 29Fewer
Stopped
NCT03976544TerminatedSpontaneous abortion
safety
NCT04865029TerminatedCOVID-19
Lack of enrollment due to change of COVID 19 variant prevalence
NCT05980091SuspendedFemale infertility
Difficulty of enrolling and recruiting patients
Trial sponsors
Company1 trialPhase 31,845 people
Centro A.F. de Estudios Tecnologicos
Company1 trialPhase 2/3103 people
Company1 trialPhase 2271 people
Company1 trialPhase 240 people
Company1 trialPhase 130 people
Universitair Ziekenhuis Brussel
2 trialsPhase 4662 people
University of North Carolina, Chapel Hill
2 trialsPhase 4104 people
Peking Union Medical College Hospital
1 trialPhase 41,200 people