madman
Super Moderator
Review of menopausal hormone therapy with estradiol and progesterone versus other estrogens and progestins (2022)
Shelli Graham, David F. Archer, James A. Simon, Kathleen M. Ohleth & Brian Bernick
ABSTRACT
Objective: The objective of the present document was to review/summarize reported outcomes compared between menopausal hormone therapy (MHT) containing estradiol (E2) versus other estrogens and MHT with progesterone (P4) versus progestins (defined as synthetic progestogens).
Methods: PubMed and EMBASE were systematically searched through February 2021 for studies comparing oral E2 versus oral conjugated equine estrogens (CEE) or P4 versus progestins for endometrial outcomes, venous thromboembolism (VTE), cardiovascular outcomes, breast outcomes, cognition, and bone outcomes in postmenopausal women.
Results: A total of 74 comparative publications were identified/summarized. Randomized studies suggested that P4 and progestins are likely equally effective in preventing endometrial hyperplasia/ cancer when used at adequate doses. E2- versus CEE-based MHT had a similar or possibly better risk profile for VTE and cardiovascular outcomes, and P4- versus progestin-based MHT had a similar or possibly better profile for breast cancer and cardiovascular outcomes. E2 may potentially protect better against age-related cognitive decline and bone fractures versus CEE; P4 was similar or possibly better versus progestins for these outcomes. Limitations are that many studies were observational and some were not adequately powered for the reported outcomes.
Conclusions: Evidence suggests a differential effect of MHT containing E2 or P4 and those containing CEE or progestins, with some evidence trending to a potentially better safety profile with E2 and/or P4.
Introduction
Menopausal hormone therapy (MHT) with estrogen alone or in combination with a progestogen is widely used to prevent or treat menopause-related hot flushes, night sweats, dyspareunia, vaginal dryness, and osteoporosis in postmenopausal women [1]. The most commonly prescribed estrogens are estradiol (E2) and conjugated equine estrogens (CEE), while the common progestogen choices include natural progesterone (P4) and those derived from progesterone or testosterone, such as medroxyprogesterone acetate (MPA) and norethisterone acetate (NETA) (i.e. progestins, defined as synthetic progestogens).
Results from the Women’s Health Initiative (WHI) study of CEE plus MPA raised safety concerns of MHT [2, 3]. Many women discontinued MHT, especially oral estrogens or estrogens/ progestins, following these publications [4], and use of E2- and P4-containing MHT increased [5].
*The objective here was to review and summarize clinical data from studies/publications directly comparing the effects of oral E2 versus CEE and P4 versus progestins on endometrial outcomes, venous thromboembolism (VTE), cardiovascular disease (CVD) outcomes, stroke, breast outcomes, cognition, bone outcomes, vasomotor symptom (VMS), and quality of life (QOL).
Results
Article review
Twenty-eight articles comparing oral E2 versus CEE [7–34] and 48 articles comparing oral P4 versus progestins were identified (3 studies had both comparisons; Figure 1) with relevant outcomes [21, 28, 34–79]. Among these articles, 32 reported findings from prospective, randomized studies or RCTs [7, 22–25, 51–77]; 19 from prospective, observational/interventional trials [11–18, 26, 33, 36, 43–50]; 18 from retrospective or cross-sectional, observational studies [8, 19–21, 27–32, 34, 35, 37–40, 78, 79]; and 4 from meta-analyses [9, 10, 41, 42]. A recently presented retrospective observational study comparing E2/P4 versus CEE/MPA was also included [80].
Endometrial outcomes
Details of the clinical studies included in this section can be found in Table 1.
*Thickness, hyperplasia, and cancer
*Uterine bleeding
Cardiovascular and thrombotic outcomes
Details of the design and results of the clinical studies included in this section can be found in Table 2.
*VTE and coagulation factors
*CVD Outcomes
*Lipids
*Blood pressure
Breast
Details of the clinical studies included in this section can be found in Table 3.
*Breast cancer
*Breast density and breast tenderness
*Cognition
*Bone
*Menopausal symptoms and QOL
Conclusion
Current evidence supports that MHT containing E2 and/or P4 is a safe and effective MHT option, and provides a similar and possibly better safety profile for some endpoints compared with CEE-based or progestin-based MHT.
Shelli Graham, David F. Archer, James A. Simon, Kathleen M. Ohleth & Brian Bernick
ABSTRACT
Objective: The objective of the present document was to review/summarize reported outcomes compared between menopausal hormone therapy (MHT) containing estradiol (E2) versus other estrogens and MHT with progesterone (P4) versus progestins (defined as synthetic progestogens).
Methods: PubMed and EMBASE were systematically searched through February 2021 for studies comparing oral E2 versus oral conjugated equine estrogens (CEE) or P4 versus progestins for endometrial outcomes, venous thromboembolism (VTE), cardiovascular outcomes, breast outcomes, cognition, and bone outcomes in postmenopausal women.
Results: A total of 74 comparative publications were identified/summarized. Randomized studies suggested that P4 and progestins are likely equally effective in preventing endometrial hyperplasia/ cancer when used at adequate doses. E2- versus CEE-based MHT had a similar or possibly better risk profile for VTE and cardiovascular outcomes, and P4- versus progestin-based MHT had a similar or possibly better profile for breast cancer and cardiovascular outcomes. E2 may potentially protect better against age-related cognitive decline and bone fractures versus CEE; P4 was similar or possibly better versus progestins for these outcomes. Limitations are that many studies were observational and some were not adequately powered for the reported outcomes.
Conclusions: Evidence suggests a differential effect of MHT containing E2 or P4 and those containing CEE or progestins, with some evidence trending to a potentially better safety profile with E2 and/or P4.
Introduction
Menopausal hormone therapy (MHT) with estrogen alone or in combination with a progestogen is widely used to prevent or treat menopause-related hot flushes, night sweats, dyspareunia, vaginal dryness, and osteoporosis in postmenopausal women [1]. The most commonly prescribed estrogens are estradiol (E2) and conjugated equine estrogens (CEE), while the common progestogen choices include natural progesterone (P4) and those derived from progesterone or testosterone, such as medroxyprogesterone acetate (MPA) and norethisterone acetate (NETA) (i.e. progestins, defined as synthetic progestogens).
Results from the Women’s Health Initiative (WHI) study of CEE plus MPA raised safety concerns of MHT [2, 3]. Many women discontinued MHT, especially oral estrogens or estrogens/ progestins, following these publications [4], and use of E2- and P4-containing MHT increased [5].
*The objective here was to review and summarize clinical data from studies/publications directly comparing the effects of oral E2 versus CEE and P4 versus progestins on endometrial outcomes, venous thromboembolism (VTE), cardiovascular disease (CVD) outcomes, stroke, breast outcomes, cognition, bone outcomes, vasomotor symptom (VMS), and quality of life (QOL).
Results
Article review
Twenty-eight articles comparing oral E2 versus CEE [7–34] and 48 articles comparing oral P4 versus progestins were identified (3 studies had both comparisons; Figure 1) with relevant outcomes [21, 28, 34–79]. Among these articles, 32 reported findings from prospective, randomized studies or RCTs [7, 22–25, 51–77]; 19 from prospective, observational/interventional trials [11–18, 26, 33, 36, 43–50]; 18 from retrospective or cross-sectional, observational studies [8, 19–21, 27–32, 34, 35, 37–40, 78, 79]; and 4 from meta-analyses [9, 10, 41, 42]. A recently presented retrospective observational study comparing E2/P4 versus CEE/MPA was also included [80].
Endometrial outcomes
Details of the clinical studies included in this section can be found in Table 1.
*Thickness, hyperplasia, and cancer
*Uterine bleeding
Cardiovascular and thrombotic outcomes
Details of the design and results of the clinical studies included in this section can be found in Table 2.
*VTE and coagulation factors
*CVD Outcomes
*Lipids
*Blood pressure
Breast
Details of the clinical studies included in this section can be found in Table 3.
*Breast cancer
*Breast density and breast tenderness
*Cognition
*Bone
*Menopausal symptoms and QOL
Conclusion
Current evidence supports that MHT containing E2 and/or P4 is a safe and effective MHT option, and provides a similar and possibly better safety profile for some endpoints compared with CEE-based or progestin-based MHT.
