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Life Sciences Jul 2023Medroxyprogesterone acetate (MPA) is the most common fertility-sparing treatment in patients with early-stage endometrial cancer. If MPA treatment fails, hysterectomy is...
AIMS
Medroxyprogesterone acetate (MPA) is the most common fertility-sparing treatment in patients with early-stage endometrial cancer. If MPA treatment fails, hysterectomy is recommended. Thus, there is an urgent need for novel treatment approaches for MPA-resistant endometrial cancer patients who wish to preserve their fertility. Ferroptosis is a recently discovered type of regulated cell death caused by the excessive accumulation of reactive oxygen species (ROS), followed by aberrant lipid peroxidation. Recent studies have shown that inducing ferroptosis is a potential therapeutic strategy for cancer. However, the role of ferroptosis in endometrial cancer treatment remains to be discussed. We therefore investigated the effects of ferroptosis inducers on MPA-resistant endometrial cancer cells.
MAIN METHODS
The levels of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), the main mediators of ferroptosis, were examined. Cell viability was evaluated after treatment with the ferroptosis inducers sulfasalazine, erastin, or RSL3. The degree of intracellular oxidative stress after treatment with these drugs was evaluated by the glutathione level, ROS level, ferrous iron level, lipid peroxidation and changes in mitochondrial morphology. The effect of ferroptosis inducers in vivo was also examined.
KEY FINDINGS
The expression of SLC7A11 and GPX4 in MPA-resistant ECC-1 cells decreased in comparison to parental ECC-1 cells. Sulfasalazine, erastin, and RSL3 significantly reduced cell viability and increased intracellular oxidative stress in MPA-resistant ECC-1 cells. Ferroptosis inducers also suppressed in vivo tumor growth more effectively in MPA-resistant ECC-1.
SIGNIFICANCE
Treatment with ferroptosis inducers could be a novel therapeutic approach for MPA-resistant endometrial cancer.
Topics: Female; Humans; Ferroptosis; Medroxyprogesterone Acetate; Reactive Oxygen Species; Sulfasalazine; Endometrial Neoplasms
PubMed: 37160245
DOI: 10.1016/j.lfs.2023.121753 -
Expert Opinion on Pharmacotherapy Jun 2009Medroxyprogesterone acetate (MPA) is a synthetic, orally active derivative of the natural steroid hormone progesterone, widely used in oncology both in the endocrine... (Review)
Review
BACKGROUND
Medroxyprogesterone acetate (MPA) is a synthetic, orally active derivative of the natural steroid hormone progesterone, widely used in oncology both in the endocrine treatment of hormone-related cancers and as supportive therapy in the cachexia syndrome.
OBJECTIVE
The anticachectic mechanisms of medroxyprogesterone, beyond its endocrine activity, are described to explain its therapeutic efficacy in the treatment of cachexia.
METHODS
After reviewing its pathophysiology and preclinical studies, the main clinical trials on the use of medroxyprogesterone acetate in cancer cachexia, are reviewed.
RESULTS/CONCLUSIONS
Progestagens, including MPA, are at present the only approved drugs in Europe for the clinical treatment of cancer-related anorexia/cachexia syndrome. Placebo-controlled trials on the effect of MPA on cachexia have generally reported an improvement of both anorexia and body weight as well as of quality-of-life parameters. However, the weight gain was due to increased body fat, while fat-free mass was not significantly influenced by MPA treatment. Moreover, very recently the combination of MPA with other new anticachectic agents has been suggested as a way of ameliorating their efficacy in the treatment of cachexia.
Topics: Animals; Cachexia; Humans; Medroxyprogesterone Acetate; Neoplasms
PubMed: 19445562
DOI: 10.1517/14656560902960162 -
CMAJ : Canadian Medical Association... Aug 2021
Topics: Adolescent; Bone Density; Canada; Contraception; Contraceptive Agents, Female; Desogestrel; Female; Humans; Intrauterine Devices, Copper; Levonorgestrel; Long-Acting Reversible Contraception; Medroxyprogesterone Acetate; Pregnancy; Pregnancy, Unplanned; Sexually Transmitted Diseases
PubMed: 34373270
DOI: 10.1503/cmaj.202413 -
Contraception Mar 1994Depo-Provera (depot-medroxyprogesterone acetate or DMPA), administered either subcutaneously or intramuscularly, has undergone a thorough toxicological evaluation in a... (Review)
Review
Depo-Provera (depot-medroxyprogesterone acetate or DMPA), administered either subcutaneously or intramuscularly, has undergone a thorough toxicological evaluation in a number of animal species. DMPA has been tested in short- and long-term toxicity studies in rodents, rabbits, and monkeys. It has been examined for its effects on reproduction in mice, rats, and rabbits, and for carcinogenic potential in rats, mice, beagle dogs, and rhesus monkeys. Genotoxicity tests have been performed in vitro and in vivo. This paper describes the toxicology data submitted to the US FDA in support of the New Drug Application (NDA) for Depo-Provera as well as data published in the literature. When interpreted in the light of the available pharmacokinetic information, these data demonstrate that DMPA is not significantly different from other contraceptive progestogens in its toxic and tumorigenic potential.
Topics: Animals; Female; Medroxyprogesterone Acetate; Mutagenesis; Neoplasms, Experimental; Pregnancy
PubMed: 8200213
DOI: 10.1016/0010-7824(94)90037-x -
Bulletin of the World Health... 1993Depot-medroxyprogesterone acetate (DMPA) is a long-acting progestational contraceptive, which is administered by injection. It was developed in the mid-1960s, when it... (Review)
Review
Depot-medroxyprogesterone acetate (DMPA) is a long-acting progestational contraceptive, which is administered by injection. It was developed in the mid-1960s, when it was seen as a method that would be particularly useful for women seeking reversible contraception who had difficulty taking a pill every day. DMPA has been shown to be a highly effective contraceptive, and it has proved acceptable in a variety of settings. The drug is licensed as a contraceptive in more than 90 countries and has been widely used in a number of them, such as Thailand and New Zealand. On a worldwide basis, the licensing, acceptability, and prevalence of use have been influenced by concern that DMPA may increase the risk of cancer. Cancer of the breast has been a particular concern. This Memorandum reviews comprehensively the results of toxicological tests in animals and epidemiological studies in humans concerning the carcinogenicity of DMPA.
Topics: Animals; Delayed-Action Preparations; Drug Approval; Epidemiologic Methods; Humans; Medroxyprogesterone Acetate; Neoplasms; Patient Acceptance of Health Care
PubMed: 8313485
DOI: No ID Found -
Medical Science Monitor : International... Jun 2022BACKGROUND Abnormal uterine bleeding (AUB) lowers the quality of life of women. This study attempted to determine which treatment protocol of medroxyprogesterone acetate...
BACKGROUND Abnormal uterine bleeding (AUB) lowers the quality of life of women. This study attempted to determine which treatment protocol of medroxyprogesterone acetate (MPA), 15 vs 10 day-administration in a luteal phase, provides better outcomes in women with ovulatory dysfunction-related AUB (AUB-O). MATERIAL AND METHODS The study included a total of 52 patients with AUB-O: Women in Group A were given MPA between days 11 and 25 of the menstrual cycle (15-day protocol), whereas women in Group B were given MPA between days 16 and 25 (10-day protocol). Outcomes were compared between the 2 groups. RESULTS Women in group B, compared with those in group A, more often showed regular menstrual cycles and decrement of AUB. In group B, 3 cycles of treatment were sufficient to achieve AUB-stop (p<0.05). Post-treatment hemogram parameters and surgical treatment requirements were not different between the 2 groups. CONCLUSIONS In the second half of the cycle/predicted luteal phase, 10-day cyclic use of MPA (the group B) better regulated the menstrual cycle and more frequently stopped AUB-O.
Topics: Clinical Protocols; Female; Humans; Medroxyprogesterone Acetate; Menstrual Cycle; Quality of Life; Uterine Hemorrhage
PubMed: 35746846
DOI: 10.12659/MSM.936727 -
The Journal of Steroid Biochemistry and... Jul 2014Medroxyprogesterone acetate (MPA) has been in clinical use for over 30 years, and was generally considered to be safe until the results of long-term studies of... (Review)
Review
Medroxyprogesterone acetate (MPA) has been in clinical use for over 30 years, and was generally considered to be safe until the results of long-term studies of postmenopausal hormone therapy (HT) using treatment with conjugated equine estrogens (CEE) combined with MPA and CEE alone suggested that MPA, and perhaps other progestogens, may play a role in the increased risk of breast cancer and cardiovascular diseases. This review examines critically the safety of MPA in terms of breast cancer and cardiovascular disease risk, and its effects on brain function. Research into mechanisms by which MPA might cause adverse effects in these areas, combined with the available clinical evidence, suggests a small increase in relative risk for breast cancer and stroke, and a decline in cognitive function, in older women using MPA with an estrogen for postmenopausal HT. However, short-term (less than 5 years) use of MPA with an estrogen in the years immediately after the onset of menopause for the management of vasomotor symptoms does not appear to be associated with any increased risk of these disorders.
Topics: Animals; Blood Coagulation; Brain; Breast Neoplasms; Cardiovascular Diseases; Cognition; Estrogen Replacement Therapy; Female; Humans; Medroxyprogesterone Acetate; Postmenopause
PubMed: 24291402
DOI: 10.1016/j.jsbmb.2013.11.011 -
The Primary Care Companion For CNS... Nov 2023
Topics: Humans; Medroxyprogesterone Acetate; Paraphilic Disorders; Sex Offenses
PubMed: 37976224
DOI: 10.4088/PCC.23cr03558 -
The Journal of Family Planning and... Apr 2013
Topics: Contraceptive Agents, Female; Female; Humans; Injections, Intramuscular; Injections, Subcutaneous; Medroxyprogesterone Acetate; Self Administration; Treatment Outcome
PubMed: 23493590
DOI: 10.1136/jfprhc-2012-100517 -
Contraception Aug 2003Depot-medroxyprogesterone acetate (Depo-Provera(R)) is a highly effective, nondaily hormonal contraceptive option that has been available in the United States for a... (Review)
Review
Depot-medroxyprogesterone acetate (Depo-Provera(R)) is a highly effective, nondaily hormonal contraceptive option that has been available in the United States for a decade, and worldwide for 40 years. Benefits and risks of hormonal therapy are often under scrutiny; however, long-term clinical experience has established the safety of this long-acting contraceptive. This article reviews the contraceptive efficacy, potential noncontraceptive health benefits and long-term safety of with regard to risk of cardiovascular events, breast and gynecologic malignancy and osteopenia. Comparisons with other hormonal contraceptives are made as clinically appropriate. Common patient management issues, including effects on menstrual cycle, body weight and mood, are also addressed. Finally, this review provides recommendations for appropriate patient selection.
Topics: Contraceptive Agents, Female; Female; Humans; Medroxyprogesterone Acetate
PubMed: 12954518
DOI: 10.1016/s0010-7824(03)00136-7