Premphase (conjugated estrogens/medroxyprogesterone acetate) / Pfizer - LARVOL DELTA

Major adverse cardiovascular events risk in menopausal women treated with oral estradiol/micronized progesterone versus conjugated estrogens/medroxyprogesterone: a claims data analysis in the USA. (PubMed, Climacteric) - "In the IPT-weighted analyses, MACE rates were 23.5 versus 85.4 per 10,000 women-years among women treated with E2/P4 and CEE/MPA (IPT-weighted incidence rate ratio [IRR] 0.28, 95% confidence interval [CI] 0.17 - 0.45; IPT-weighted hazard ratio [HR] 0.37, 95% CI 0.27 - 0.50). Real-world evidence suggests that the MACE risk is significantly lower among women treated with E2/P4 compared to CEE/MPA."

Adverse events • Journal • Cardiovascular

The zymogenic form of SARS-CoV-2 main protease: A discrete target for drug discovery. (PubMed, J Biol Chem) - "Additionally, we observed positive modulation of precursor activity at low concentrations of inhibitors. Our findings help expand understanding of the SARS-CoV-2 viral life cycle and may facilitate development of strategies to target preMpro for inhibition or premature activation of Mpro."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Hormone replacement therapy perspectives. (PubMed, Front Glob Womens Health) - "We propose that these formulations have the "black box" warning removed so that doctors feel more confident in prescribing these products for symptoms of menopause and chronic conditions such as cardiovascular health. We propose eliminating the sale of products containing medroxyprogesterone acetate (MPA) because of the increased risk of heart attacks and breast cancers associated with this medication."

Journal • Breast Cancer • Cardiovascular • Myocardial Infarction • Oncology • Solid Tumor • Women's Health

MAJOR ADVERSE CARDIOVASCULAR EVENT RISK IN MENOPAUSAL WOMEN TREATED WITH ORAL ESTRADIOL/MICRONISED PROGESTERONE VERSUS CONJUGATED ESTROGENS/ MEDROXYPROGESTERONE ACETATE: A CLAIMS DATA ANALYSIS IN THE UNITED STATES (ISGE 2024) - "The E2/P4 or CEE/MPA cohorts included 6,520 and 29,426 women respectively (mean follow-up: 1.2 and 1.4 years). At index date, women initiated on E2/P2 were younger (mean age: 54 vs 56 y for CEE/MPA), had less cardiovascular disease (34 vs 44%), and less hypercholesterolemia (24 vs 31%). Covariates were balanced post-IPT weighting."

Adverse events • Clinical • Cardiovascular • Congestive Heart Failure • Dyslipidemia • Heart Failure • Ischemic stroke • Metabolic Disorders • Myocardial Infarction • Women's Health

Drugs for menopausal symptoms. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal

Venous thromboembolism risk in menopausal women treated with oral estradiol/micronised progesterone versus conjugated estrogens/medroxyprogesterone: a claims data analysis in the united states (ISGE 2022) - "Results from these exploratory analyses indicate that the VTE risk may be lower among women initiated on E2/P4 compared to CEE/MPA. Further research is warranted to confirm this finding."

Clinical • Cardiovascular • Dyslipidemia • Metabolic Disorders • Venous Thromboembolism • Women's Health

The effect of hormone therapy on breast density following risk-reducing salpingo-oophorectomy in women with an increased risk for breast and ovarian cancer. (PubMed, Menopause) - "A decline in breast density is seen after premenopausal RRSO despite the use of both CEE + MPA or tibolone, although lower breast density is seen after tibolone use."

Clinical • Journal • Breast Cancer • Gynecology • Oncology • Ovarian Cancer • Solid Tumor

"Cranked out Rxs one right after the other 20 years ago for Prempro. Today, haven't seen an Rx for it in years" (@JasonSkelton79)

MHT and cognition.. CNGOF and GEMVi clinical practice guidelines (PubMed, Gynecol Obstet Fertil Senol) - "The molecules which are used in France, 17-beta estradiol and natural progesterone (or its isomer, dydrogesterone) are very different from the equine conjugated estrogens and medroxyprogesterone acetate used in the WHI. Moreover, cognition remains relatively stable at the beginning of menopause since the cognitive reserve as well as the different compensation circuits allow compensation for estrogen deficiency. This does not in any way prejudge a possible positive effect of MHT on AD, which is very difficult to demonstrate, as the age of onset of this dementia is very late, 20 or 30 years after the initiation of treatment."

Clinical • Clinical guideline • Alzheimer's Disease • Cardiovascular • CNS Disorders • Dementia

Preventing estrogen receptor alpha-positive breast cancer outgrowth with the use of hormone replacement therapy (AACR 2018) - "...Follow-up sudies suggest that breast cancer cases from PremPro treatment were primarily due to the outgrowth of occult tumors, not the formation of new disease. Duavee, a more recent form of HRT that combines CE and bazedoxifene (BZA), a selective estrogen receptor modulator (SERM) and degrader (SERD), has been approved by the FDA for treatment of moderate to severe hot flashes and to reduce the risk of osteoporosis...In addition, CE+BZA was able to decrease the rate of tumor growth in an ER-positive patient-derived xenograft (PDX) mouse model. An improved understanding of the molecular mechanisms of CE+BZA action in hormone sensitive breast cancer cell and animal models should have important implications for women considering HRT."

Hormone Receptor Breast Cancer

Drugs for menopausal symptoms. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal

Novel Melatonin, Estrogen, and Progesterone Hormone Therapy Demonstrates Anti-Cancer Actions in MCF-7 and MDA-MB-231 Breast Cancer Cells. (PubMed, Breast Cancer (Auckl)) - "A novel melatonin, estrogen, and progesterone hormone therapy was developed as a safe bio-identical alternative hormone therapy for menopausal women based on the Women's Health Initiative findings that PremPro™ increased breast cancer risk and mortality of all types of breast cancer in postmenopausal women...Inhibition of MEK1/2 and 5 using PD98059 and BIX02189, respectively, inhibited proliferation and migration in MDA-MB-231 cells and proliferation in MCF-7 cells; however, when combined with melatonin, estrogen, and progesterone, BIX02189 blocked melatonin, estrogen, and progesterone-mediated inhibition of migration in MCF-7 cells and induced Elf-5. For MDA-MB-231 cells, BIX02189 combined with melatonin, estrogen, and progesterone inhibited proliferation and increased pERK1/2 and β1-INTEGRIN; levels of pERK5 remained low/nearly absent in both breast cancer lines. These findings demonstrate novel anti-cancer actions of melatonin, estrogen, and progesterone in ER+..."

Journal • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • Women's Health • HER-2

Endometrial cancer: The unopposed estrogen hypothesis (Empowher) - Postmenopausal HRT became popular in 1970's, & was followed by rise in endometrial cancer in 1980's; These initial pills were estrogen only; Increased cancer risk is factor of 2 to 10, depending on how many years hormones are used; Progestins were added to most hormone replacement pills like prempro to reduce risk; Mueck reported that combined oral contraceptives reduce risk of endometrial cancer, while Karageorgi reported that postmenopausal HRT increases risk

Analysis • None

Pfizer settled about half of Prempro cases, adds to reserve (Businessweek) - Pfizer has settled almost half of the lawsuits over its menopause drugs & increased the funds set aside to resolve the cases, the company said in a regulatory filing

Lawsuit update • Vaginal Atrophy

Pfizer expects to wrap up Prempro suits for $1.2B total (Fierce Pharma) - Drugmaker has paid $896M to wrap up about 60% of the patient lawsuits; That's about 6,000 cases, all alleging that its hormone-replacement drugs caused breast cancer; Pfizer has also set aside more money $330M to cover rest of its Prempro liability

Product liability lawsuit • Vaginal Atrophy

Estradiol/progesterone (Bijuva) for menopausal vasomotor symptoms. (PubMed, Med Lett Drugs Ther) - No abstract available.

Journal

Colorectal cancer screening. (PubMed, Med Lett Drugs Ther) - No abstract available.

Journal

Human versus non-human sex steroid use in hormone replacement therapies part 1: Preclinical data. (PubMed, Mol Cell Endocrinol) - "However, adverse findings from the Women's Health Initiative (WHI) studies that examined the 2 major forms of HRT in use in the US at that time - Premarin (conjugated equine estrogens; CEE) and Prempro (CEE + medroxyprogesterone acetate; MPA), cast a shadow over the use of any form of HRT. Moreover, unlike P, MPA is clearly antagonistic of the positive effects of E and CEE on tissue function. These data indicate that minor chemical changes to human sex steroids result in physiologically distinct actions that are not optimal for tissue health and functioning."

Journal • Preclinical • Review

Uterine bleeding rates with hormone therapies in menopausal women with vasomotor symptoms (EMAS 2019) - P3; " Bleeding data were identified for Bijuva (E2/P4 [mg/mg] 1/100), Prempro ® (CEE/MPA [mg/mg] 0.625/5; 0.625/2.5; 0.45/1.5; 0.3/1.5), Activella ® (E2/NETA [mg/mg] 1/0.5; 0.5/0.1) Angeliq ® (E2/DRSP [mg/mg] 1/0.5), Climara Pro ® (E2/LNG [mg/mg] 0.045/0.015) and CombiPatch ® (E2/NETA [mg/mg] 0.05/0.14; 0.05/0.25). Comparing amenorrhea rates over time of E2/P4 from REPLENISH with those reported in published product information for other HT with synthetic progestins in separate studies, using different methodologies, suggests a potentially improved bleeding profile with E2/P4. Endometrial bleeding incidence with CHT products (other than in one survey) has not been published, even though many women choose to use them to treat their VMS."

Clinical

Predictors Of Vaginal/Uterine Bleeding With Oral TX-001HR (Estradiol and Progesterone) Capsules Taken For Menopausal Vasomotor Symptoms (ENDO 2019) - P3; "...Cumulative amenorrhea rates (no bleeding or spotting for 13 cycles) ranging from 23% to 49% with current HT options1-3 are relatively lower than the 56% to 73% observed in the REPLENISH trial.4 The REPLENISH trial (NCT01942668) was a 12-month, phase 3, randomized, double-blind, placebo-controlled, multicenter trial that evaluated TX-001HR (bioidentical 17β-estradiol and progesterone [E2/P4] combined in a single, oral softgel capsule; 1 mg E2/100 mg P4 FDA approved as BIJUVATM; TherapeuticsMD, Boca Raton, FL) vs placebo in 1835 menopausal women (40−65 y; intact uterus) for the treatment of menopausal, moderate to severe vasomotor symptoms (VMS)...Prempro tablets PI...Activella tablets PI...Angeliq Tablets PI...Obstet Gynecol. 2018;132:161-170."

Predictors Of Vaginal/Uterine Bleeding With Oral TX-001HR (Estradiol and Progesterone) Capsules Taken For Menopausal Vasomotor Symptoms (ENDO 2019) - P3; "...Cumulative amenorrhea rates (no bleeding or spotting for 13 cycles) ranging from 23% to 49% with current HT options1-3 are relatively lower than the 56% to 73% observed in the REPLENISH trial.4 The REPLENISH trial (NCT01942668) was a 12-month, phase 3, randomized, double-blind, placebo-controlled, multicenter trial that evaluated TX-001HR (bioidentical 17β-estradiol and progesterone [E2/P4] combined in a single, oral softgel capsule; 1 mg E2/100 mg P4 FDA approved as BIJUVATM; TherapeuticsMD, Boca Raton, FL) vs placebo in 1835 menopausal women (40−65 y; intact uterus) for the treatment of menopausal, moderate to severe vasomotor symptoms (VMS)...Prempro tablets PI...Activella tablets PI...Angeliq Tablets PI...Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*"