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Prg4.4
Progesterone – Forschung
Überwiegend Mechanismus / Beobachtung
21 begutachtete Studien
Was die Evidenz sagt
Überwiegend Mechanismus / Beobachtung
Die meisten Studien zu Progesterone sind mechanistisch oder beobachtend statt RCTs, die einen klinischen Effekt messen — betrachte die Ergebnisse als vorläufig.
Die meiste Evidenz stammt aus hochwertigen Meta-Analysen und randomisierten Studien, veröffentlicht 1996–2026 mit einer typischen Studiengröße von 884 Teilnehmenden.
Basierend auf 21 Studien · 3 Meta-Analysen · 4 RCTs · 27,658 Teilnehmende insgesamt
Konfidenz
Hohe Konfidenz
Nach Outcome
Endometrial protection & menopauseEine placebokontrollierte RCT ergab, dass orales mikronisiertes Progesteron Hitzewallungen und nächtliches Schwitzen reduzierte; es stellte zudem eine normale Schlafarchitektur bei postmenopausalen Frauen wieder her · Nächte bis Wochen · Die Zugabe von Progesteron zu Östrogen verhindert Endometriumhyperplasie/-karzinom (PEPI); standardmäßige Unterstützung der Lutealphase, die die Schwangerschaftsergebnisse bei IVF verbessert (Cochrane) · Während der gesamten Anwendung
Überwiegend Mechanismus / Beobachtung18 Studien
Luteal support & early pregnancyStandardmäßige Unterstützung der Lutealphase bei assistierter Reproduktion; eine Cochrane-Übersichtsarbeit von 94 RCTs ergab, dass es die Schwangerschaftsergebnisse gegenüber Placebo verbessert · Während der IVF-Lutealphase
Überwiegend Mechanismus / Beobachtung8 Studien
Safety profile
Überwiegend Mechanismus / Beobachtung4 Studien
Sleep (menopausal)
Zu wenige bewertete Studien1 Studie
Aktives Forschungsgebiet
14 Studien in den letzten 5 Jahren · Neueste Meta-Analyse: 2026
199620112026
1Meta-Analysen=884 · large study2026
While the specific exercise modalities show potential advantages for improving PCOS-related outcomes, the findings should be interpreted with caution as preliminary insights due to the low or very low certainty of the overall evidence.
Hu S et al. · Reproductive biology and endocrinology : RB&E (2026)
Aerobic exercise also ranked highest for progesterone (SUCRA = 98.90%; SMD: -0.51; 95% CrI: -0.95, -0.07).
While the specific exercise modalities show potential advantages for improving PCOS-related outcomes, the findings should be interpreted with caution as preliminary insights due to the low or very low certainty of the overall evidence.
Further large-scale, rigorously designed studies are required to confirm the comparative effectiveness of different exercise modalities.
Ultimately, MHT should be viewed not as a one-size-fits-all therapy, but as a personalized, evidence-informed strategy that supports the health and quality of life of menopausal women.
Finks SW et al. · Pharmacotherapy (2026)
Further evidence highlights potential cardiovascular and cognitive benefits when MHT is initiated within 10 years of menopause.
Clinicians caring for menopausal women should promote individualized, evidence-based MHT through education, therapeutic selection, shared decision making, and ongoing monitoring.
Continued research is needed to refine dosing targets, evaluate long-term preventive outcomes, and expand evidence for modern formulations beyond WHI-era therapies.
Natural progesterone supports pregnancy by preventing miscarriages, preterm labor, and LPD through its direct and indirect immunomodulatory mechanisms.
Mehta P et al. · The journal of obstetrics and gynaecology research (2026)
Natural progesterone supports pregnancy by preventing miscarriages, preterm labor, and LPD through its direct and indirect immunomodulatory mechanisms.
Clinically, it is well-tolerated with no serious or unexpected adverse events.
However, gaps remain in fully understanding its effectiveness, emphasizing the need for further research.
This aims to provide new directions and evidence for advancing the precision treatment of uterine fibroids.
Wang S et al. · Redox report : communications in free radical research (2026)
Therefore, we reviewed the molecular mechanisms underlying hormone-OS interactions within the E-P-OS network and elucidated its pathological effects in promoting uterine fibroid progression.
The integrated perspective lays the theoretical foundation for developing novel therapies that simultaneously block hormone signaling and counteract oxidative damage.
Additionally, we summarized current clinical strategies for hormone therapy and antioxidant treatment, identified potential combination therapy approaches, and explored key challenges in their clinical translation.
International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.
Saccone G et al. · International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics (2026)
Vaginal and subcutaneous progesterone offer comparable efficacy to intramuscular formulations, with better tolerability and compliance.
Current evidence does not support universal progesterone supplementation in early pregnancy, but individualized treatment might be considered for women at increased risk, based on clinical history.
Future research should focus on identifying reliable markers of luteal deficiency, refining patient selection and comparing different administration routes and serum thresholds.
Standardized diagnostic frameworks and well designed prospective studies are needed to clarify prognostic factors and optimize therapeutic strategies to improve reproductive outcomes.
Manem N et al. · Current opinion in obstetrics & gynecology (2026)
Systematic review examining Progesterone efficacy
Published in Current opinion in obstetrics & gynecology (2026)
Overall, MHT use in women with or at risk for pulmonary disease should be individualized, integrating symptom burden, cardiometabolic and respiratory risk, disease phenotype and formulation/route.
Hipólito Rodrigues MA et al. · Climacteric : the journal of the International Menopause Society (2026)
In pulmonary hypertension, evidence is conflicting, and clinical decisions must weigh thrombotic risk, strongly influenced by the route of estrogen administration.
Studies on obstructive sleep apnea and sleep-disordered breathing suggest possible modest benefits of MHT in selected populations but are methodologically heterogeneous.
For lung cancer, large cohorts, meta-analyses and randomized trials essentially show no clear increase in incidence with MHT and suggest potential survival advantages in some subgroups.
This narrative review provides an updated overview of the clinical benefits of HRT regimens based on E2/P4, with a focus on their impact on endometrial thickness, venous thromboembolism (VTE), cardiovascular diseases (CVDs), breast cancer risk, cognitive effects, bone protection, and quality of life (QoL).
Foschi M, Groccia G, Rusce ML, Medaglia C, Aio C, Sponzilli A, Setti V, Battipaglia C, Genazzani AD. · Journal of clinical medicine (2025)
Standard regimens generally combine 17β-estradiol (E2) or conjugated equine estrogens (CEEs) with micronized progesterone (P4) or synthetic progestins.
While synthetic progestins ensure endometrial protection against estrogen-induced stimulation of the endometrium, their impact on metabolic, cardiovascular, skeletal, and cognitive systems is heterogeneous and not always beneficial.
In contrast, progesterone, as a micronized preparation (P4), allows for more physiological effects because it is chemically identical to endogenous progesterone.
Conclusions Individualized luteal phase support with DYD supplementation in patients with low luteal serum P4 levels during an HRT cycle for FET achieves LBR comparable to those observed in patients with adequate serum P4 levels, both in this cohort study and in a complementary meta-analysis.
Cucchietti O, Mollevi C, Moulis L, Anahory T, Huberlant S, Brouillet S, Ranisavljevic N, Duraes M. · Journal of assisted reproduction and genetics (2025)
Results Insufficient P4 levels were observed in 28.9% (159/550) of the studied cycles.
LBR was comparable in both groups (24.16% [94/391] in group 1 and 27.22% [43/159] in group 2) and was not associated with the luteal support strategy (aOR 1.01, 95% CI [0.65-1.58], p = 0.96).
In the meta-analysis, the ongoing pregnancy rate was similar in both groups (aOR 1.14, 95% CI [0.91-1.42]).
Findings align with neutral cognitive and cerebrovascular outcomes in this cohort.
Kantarci K, Kara F, Tosakulwong N, Fought AJ, Schwarz CG, Senjem ML, Kendall-Thomas J, Min P, Lowe VJ, Jack CR, Kapoor E, Fields JA, Bailey KR, James TT, Faubion L, Lobo RA, Manson JE, Pal L, Hammers DB, Brinton EA, Malek-Ahmadi M, Cedars MI, Naftolin FN, Santoro N, Miller VM, Harman SM, Dowling NM, Gleason CE. · Alzheimer's & dementia : the journal of the Alzheimer's Association (2026)
Findings support the long-term safety of short-term use of mHT on brain health.
Clinical trials registration NCT00154180 Kronos Early Estrogen Prevention Study (KEEPS) HIGHLIGHTS: There were no menopausal hormone therapy-related adverse effects or benefits on amyloid beta and magnetic resonance imaging biomarkers in the long term.
Apolipoprotein E ε4 carrier status did not modify these findings.
Conclusion Oral dydrogesterone seems to be a good alternative to vaginal micronized progesterone for LPS treatment during an artificial cycle, especially in combination with a weekly injection of intramuscular progesterone in the course of oocyte donation.
Lorillon M, Robin G, Keller L, Cailliau E, Delcourt C, Simon V, Decanter C, Catteau-Jonard S. · Reproductive biology and endocrinology : RB&E (2024)
The primary endpoint was the clinical pregnancy rate.
Results Our study analysed 372 oocyte donation cycles with embryo transfer: 162 embryo transfers with DYD + IM progesterone and 210 embryo transfers with MVP + IM progesterone.
Conclusion Oral dydrogesterone seems to be a good alternative to vaginal micronized progesterone for LPS treatment during an artificial cycle, especially in combination with a weekly injection of intramuscular progesterone in the course of oocyte donation.
Trial registration The study has been retrospectively registered with the Clinical Trials registry reference number ISRCTN52148405 ( http://isrctn.org/ ).
Rinaldi L, Crescenzi F, Selman H. · BMC pregnancy and childbirth (2024)
A P ≤ 0.05 was considered statistically significant.
Results No differences were observed between the two groups in terms of pregnancy rate (Group A 34,9% vs.
Group B 35,7%), live birth rate (Group A 30,6% vs.
Unopposed estrogen is associated with increased rates of endometrial hyperplasia; the addition of a progestin... protects the endometrium.
Writing Group for the PEPI Trial · JAMA (1996)
Randomized, placebo-controlled trial of postmenopausal women assigned to placebo, conjugated estrogen alone, or estrogen plus a progestogen (including micronized progesterone)
Unopposed estrogen produced markedly higher rates of endometrial hyperplasia (a precursor to cancer); adding a progestogen, including micronized progesterone, brought hyperplasia rates back toward placebo
The foundational evidence that progesterone's role in HRT is ENDOMETRIAL PROTECTION — why any woman with a uterus on systemic estrogen needs a progestogen
Luteal phase support with progesterone... was associated with higher rates of live birth or ongoing pregnancy compared with placebo or no treatment.
van der Linden M, Buckingham K, Farquhar C, Kremer JA, Metwally M · Cochrane Database of Systematic Reviews (2015)
Cochrane systematic review and meta-analysis of 94 randomized trials (26,198 women) of luteal-phase support in assisted reproduction
Progesterone for luteal-phase support improved pregnancy outcomes versus placebo/no treatment, and adding a GnRH agonist to progesterone showed additional benefit
The top-of-pyramid synthesis anchoring progesterone's IVF luteal-support indication in pooled randomized data
The incidence of live births was not significantly higher in the progesterone group than in the placebo group... a subgroup analysis according to the number of previous miscarriages suggested a benefit.
Coomarasamy A, Devall AJ, Cheed V, Harb H, Middleton LJ, Gallos ID, et al.; PRISM Trial Investigators. · The New England journal of medicine (2019)
PRISM: a large randomized, double-blind, placebo-controlled trial of vaginal micronized progesterone in women with early-pregnancy bleeding and a viable intrauterine pregnancy
Progesterone did NOT significantly increase live births overall — an honest negative primary result
A prespecified subgroup with one or more previous miscarriages DID appear to benefit, which is the basis for the narrow, indication-specific use
Progesterone administration prevented the sleep disturbances induced by experimental sleep fragmentation and restored normal sleep in postmenopausal women.
Caufriez A, Leproult R, L'Hermite-Balériaux M, Kerkhofs M, Copinschi G · The Journal of Clinical Endocrinology and Metabolism (2011)
Randomized, double-blind, placebo-controlled crossover study of oral micronized progesterone (300 mg at bedtime) in healthy postmenopausal women
Progesterone prevented experimentally induced sleep disturbances and restored normal sleep architecture, acting as a 'physiologic' sleep regulator
Mechanistic and clinical support for the off-label menopausal-sleep use, consistent with the sedating allopregnanolone/GABA action
Estrogen-progesterone... was not associated with a significant increase in breast cancer risk, in contrast to estrogen combined with synthetic progestins.
Fournier A, Berrino F, Clavel-Chapelon F · Breast cancer research and treatment (2008)
Large prospective French E3N cohort relating different HRT regimens to breast-cancer risk in postmenopausal women
Estrogen combined with MICRONIZED PROGESTERONE (or dydrogesterone) was associated with little or no increased breast-cancer risk over several years, unlike estrogen plus synthetic progestins, which raised risk
Key evidence that the breast signal should be attributed to SYNTHETIC progestins (as in the WHI), not assumed for micronized progesterone