Progestin medroxyprogesterone acetate
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Medroxyprogesterone Acetate: Applications and Implications
Fertility-Sparing Treatment with Medroxyprogesterone Acetate
Medroxyprogesterone Acetate (MPA) in Endometrial Hyperplasia and Cancer
Medroxyprogesterone acetate (MPA) is a progestin used in fertility-sparing treatments for patients with atypical endometrial hyperplasia (AEH) and endometrial cancer (EC). Studies have shown that while MPA therapy has a high remission rate, it is also associated with a high rate of relapse. Combining MPA with metformin has been investigated to reduce relapse rates, with promising results indicating that metformin may inhibit disease relapse after remission1.
MPA in Advanced or Recurrent Endometrial Carcinoma
Efficacy of Oral MPA in Endometrial Carcinoma
MPA has demonstrated activity against advanced or recurrent endometrial carcinoma. A study comparing low-dose (200 mg/day) and high-dose (1,000 mg/day) oral MPA found that the low-dose regimen had a higher overall response rate (25%) compared to the high-dose regimen (15%). The study concluded that oral MPA is effective, particularly in patients with well-differentiated histology and positive progesterone receptor status, and that higher doses do not necessarily improve outcomes2.
Environmental and Biological Impact of MPA
Effects on Aquatic Life
MPA, along with other synthetic progestins like dydrogesterone, has been shown to adversely affect aquatic organisms such as zebrafish. Exposure to these compounds can impair reproductive capacities, cause histological alterations in gonads, and induce multiple transcriptional responses even at environmentally relevant concentrations. These findings highlight the potential environmental risks associated with the use of synthetic progestins3.
Impact on Immune Responses
MPA can modulate immune responses by decreasing Th1 and Th17 responses while increasing Th22 responses via AHR signaling. This modulation could affect susceptibility to infections and inflammatory diseases, suggesting that MPA has significant immunological effects that need to be considered in clinical use4.
Androgenic Properties and Cognitive Effects
Androgen Receptor Activity
MPA and norethisterone acetate (NET-A) have been found to act as androgen receptor (AR) agonists, unlike natural progesterone. This androgenic activity may contribute to some of the side effects observed with MPA use, such as increased risk of breast cancer and HIV-1 transmission. The differential promoter-specific actions via the AR suggest that MPA and NET-A can exert significant off-target effects5.
Cognitive Impairment in Menopausal Models
In aged surgically menopausal rats, MPA has been shown to impair memory and alter the GABAergic system. High-dose MPA, in particular, exacerbated memory retention issues and affected GAD levels in cognitive brain regions. These findings suggest that MPA may have detrimental effects on brain health and function, particularly in the context of hormone therapy6.
MPA in Gender-Affirming Therapy
Use in Transwomen
MPA is commonly used in feminizing hormone therapy for transwomen. A retrospective study found that MPA treatment was associated with minimal side effects, unchanged estradiol levels, and a significant decline in testosterone levels, which are consistent with feminization. However, some patients reported mood swings, indicating the need for further prospective studies to confirm these findings7.
Conclusion
Medroxyprogesterone acetate (MPA) is a versatile progestin with applications ranging from fertility-sparing treatments to hormone therapy in transwomen. While it has demonstrated efficacy in various clinical settings, its use is also associated with significant side effects and environmental impacts. Further research is needed to optimize its use and mitigate potential risks.
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Most relevant research papers on this topic
Medroxyprogesterone acetate plus metformin for fertility-sparing treatment of atypical endometrial hyperplasia and endometrial carcinoma: trial protocol for a prospective, randomised, open, blinded-endpoint design, dose-response trial (FELICIA trial)
Medroxyprogesterone acetate plus metformin may be an effective fertility-sparing treatment for patients with atypical endometrial hyperplasia and endometrial cancer, with metformin inhibiting disease relapse after remission.
RCT
Rigorous JournalOral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose-response study by the Gynecologic Oncology Group.
Oral medroxyprogesterone acetate 200 mg/d is a reasonable initial approach for treating advanced or recurrent endometrial carcinoma, particularly in well-differentiated and progesterone receptor-positive lesions.
RCT
Highly CitedSynthetic progestins medroxyprogesterone acetate and dydrogesterone and their binary mixtures adversely affect reproduction and lead to histological and transcriptional alterations in zebrafish (Danio rerio).
MPA and DDG and their binary mixtures negatively affect reproduction and gonad histology in zebrafish, leading to transcriptional and histological alterations at environmentally relevant concentrations.
Highly CitedMedroxyprogesterone Acetate Decreases Th1, Th17, and Increases Th22 Responses via AHR Signaling Which Could Affect Susceptibility to Infections and Inflammatory Disease
Medroxyprogesterone acetate (MPA) can inhibit Th1 responses against bacteria, fungi, and parasites, but increases IL-22 production by Th22 cells, potentially affecting susceptibility to infections and inflammation.
In Vitro StudyA comparative study of the androgenic properties of progesterone and the progestins, medroxyprogesterone acetate (MPA) and norethisterone acetate (NET-A)
MPA and NET-A, used in hormonal therapy, compete with DHT and exert significant off-target transcriptional effects via the androgen receptor, potentially contributing to some side-effects observed in clinical use.
In Vitro StudyMedroxyprogesterone acetate impairs memory and alters the GABAergic system in aged surgically menopausal rats
Medroxyprogesterone acetate (MPA) impairs memory and alters the GABAergic system in aged surgically menopausal rats, indicating negative effects for brain health and function.
Non-RCT
Animal StudyHighly CitedMedroxyprogesterone Acetate in Gender-Affirming Therapy for Transwomen: Results from a Retrospective Study.
In transwomen, minimal side effects, unchanged estradiol levels, and a decline in testosterone are associated with MPA use, consistent with feminization.
Observational StudyRigorous JournalAn updated review on the effects of depot medroxyprogesterone acetate on the mucosal biology of the female genital tract
Depot medroxyprogesterone acetate (DMPA) is a safe and effective contraceptive with low failure rates and convenient administration schedule, but its effects on the mucosal biology of the female genital tract need further investigation.
Literature ReviewClassification and pharmacology of progestins.
Progestins have diverse biological effects, ranging from contraceptive effectiveness to uterine contractions, and their classification and pharmacology are crucial for medical treatment planning.
Highly CitedProgestin-Primed Ovarian Stimulation with Dydrogesterone versus Medroxyprogesterone Acetate in Women with Polycystic Ovarian Syndrome for in vitro Fertilization: A Retrospective Cohort Study
Dydrogesterone in a PPOS protocol can achieve comparable oocyte retrieval and pregnancy outcomes to medroxyprogesterone acetate, while significantly reducing gonadotropin consumption in PCOS women undergoing IVF treatment.
Observational StudyRigorous Journal