Effects of norethindrone: A Synthesis of Findings from 17 Studies

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Original Abstract of the Article

Major Research Findings

Norethindrone has been found to have various effects on human and animal health. In 10 , it was found to improve sexual function in postmenopausal women more effectively than a combination of estradiol and norethindrone acetate. Meanwhile, 9 showed that norethindrone, when combined with estradiol, can alleviate menopausal symptoms and improve lipid profiles in postmenopausal women. On the other hand, some research indicates that norethindrone can have adverse effects on fish. 2 and 6 suggest that norethindrone can disrupt thyroid function and promote masculinization in fish. Moreover, 5 suggests that norethindrone might reduce the neuroprotective effects of progesterone in Wobbler mice. These studies highlight that while norethindrone can be beneficial for postmenopausal women, it also has the potential to cause harm to fish and mammals.

Benefits and Risks

Benefit Summary

Norethindrone can improve the quality of life for postmenopausal women by potentially improving sexual function, alleviating menopausal symptoms, and improving blood lipid levels. 10 , 9

Risk Summary

Norethindrone has the potential to harm fish and mammals. It can disrupt thyroid function and promote masculinization in fish. It might also diminish the neuroprotective effects of progesterone in mammals. 2 , 6 , 5

Comparison between Studies

Commonalities

Multiple studies consistently suggest that norethindrone can improve quality of life for postmenopausal women, but also carries the potential for adverse effects on fish and mammals.

Differences

There are inconsistencies regarding the effects of norethindrone on sexual function. While 10 suggests that norethindrone is more effective in improving sexual function than a combination of estradiol and norethindrone acetate, 9 indicates no noticeable impact on sexual function when combined with estradiol. Furthermore, the impact of norethindrone on fish varies by species. 2 and 6 demonstrate adverse effects on medaka fish, while the impact on other fish species remains unclear. The impact of norethindrone on mammals can also vary based on animal species and dosage. 5 shows a negative effect on neuroprotection in Wobbler mice, but the effects on other mammalian species are yet to be established.

Consistency and Contradictions in Findings

Although norethindrone appears beneficial for improving the quality of life in postmenopausal women, there are potential harmful effects on fish and mammals. These findings highlight the need for further research to better understand the safety and efficacy of norethindrone.

Points to Note Regarding Real-Life Applications

While norethindrone can be effective for managing menopausal symptoms, it's crucial to be aware of its potential negative impacts on fish and mammals. Consulting with a doctor and avoiding self-medication are vital when considering norethindrone. Additionally, proper disposal methods should be used for medication containing norethindrone to minimize environmental impact and potential harm to aquatic life.

Limitations of Current Research

Research regarding norethindrone is still ongoing and needs to be expanded. Notably, the long-term impacts of norethindrone use and its effects on diverse animal species require further investigation.

Future Research Directions

Future research should delve into the long-term effects of norethindrone use and its impacts on various animal species. Additionally, comprehensive studies focusing on the environmental implications of norethindrone are crucial. Such research will provide a deeper understanding of the safety and effectiveness of norethindrone.

Conclusion

Norethindrone offers potential benefits for improving the quality of life for postmenopausal women. However, it's vital to be aware of its possible adverse effects on fish and mammals. Consulting with a doctor and avoiding self-medication are crucial when considering norethindrone. Further research focusing on the long-term effects of norethindrone and its impact on diverse animal species and the environment is essential to ensure its safe and effective use.

Literature analysis of 17 papers
Positive Content
8
Neutral Content
1
Negative Content
8
Article Type
6
1
0
0
16
1.

Effects of sodium etidronate in combination with low-dose norethindrone in patients administered a long-acting GnRH agonist: a preliminary report.

Author: SurreyE S, FournetN, VoigtB, JuddH L

Bone density
Vasomotor stability
HDL cholesterol decrease
LDL/HDL ratio increase

The addition of cyclic sodium etidronate in combination with low-dose norethindrone to GnRH agonists is an effective means of ameliorating the hypoestrogenic side effects induced by GnRH agonist alone.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

4.

The effects of norethindrone on the ontogeny of gene expression along the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes in zebrafish (Danio rerio).

Author: LuoYixuan, ChenHongxing, LiDan, ZhanManjun, HouLiping, DongWu, LuoYongju, XieLingtian

Precocious effects

Norethindrone (NET) exposure altered the expression of HPA- and HPG-axes related genes in zebrafish embryos/early larvae, suggesting potential precocious effects on sexual development.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

5.

Comparative effects of progesterone and the synthetic progestin norethindrone on neuroprotection in a model of spontaneous motoneuron degeneration.

Author: Gargiulo-MonachelliGisella, MeyerMaria, LaraAgustina, GarayLaura, LimaAnalia, RoigPaulina, De NicolaAlejandro F, Gonzalez DeniselleMaria Claudia

ALS Treatment
Thymus Atrophy

This study investigated the effects of natural progesterone (PROG) and synthetic progestin norethindrone (NOR) in Wobbler mice, a model of amyotrophic lateral sclerosis (ALS). PROG showed neuroprotective effects, while NOR had detrimental effects on motor function and inflammation.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

8.

Synergistic effects of E2MATE and norethindrone acetate on steroid sulfatase inhibition: a randomized phase I proof-of-principle clinical study in women of reproductive age.

Author: PohlOliver, BestelElke, GottelandJean-Pierre

Endometriosis treatment

This study investigated the pharmacodynamics, pharmacokinetics, and safety of the steroid sulfatase (STS) inhibitor PGL2001 (E2MATE) and norethindrone acetate (NETA) in healthy women. The combination of PGL2001 and NETA showed synergistic effects on STS activity, suggesting a potential new treatment option for endometriosis.

Clinical Trial, Phase IThe first stage of clinical trials in humans. Evaluates the safety, tolerability, and pharmacokinetics of a new drug/treatment.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

9.

Effects of short-term estradiol and norethindrone acetate treatment on the breasts of normal postmenopausal women.

Author: ChengGuojun, ButlerRyan, WarnerMargaret, GustafssonJan-Åke, WilczekBrigitte, LandgrenBritt-Marie

Hot flash relief
Lipid reduction
Sweating relief

Estradiol and estrogen-progestogen treatment up-regulated progesterone receptors but did not significantly affect estrogen receptors, androgen receptor, proliferation, or breast density.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

Effects of a continuous-combined regimen of low-dose hormone therapy (oestradiol and norethindrone acetate) and tibolone on the quality of life in symptomatic postmenopausal women: a double-blind, randomised study.

Author: PolisseniAlvaro Fernando, AndradeAmaury Teixeira Leite, RibeiroLuiz Claudio, CastroIsabela Queirós, BrandãoMarcos, PolisseniFernanda, GuerraMartha de Oliveira

Hormone therapy efficacy
LD-HT efficacy
Postmenopausal QoL
Tibolone efficacy

Low-dose hormone therapy (LD-HT) improved quality of life (QoL) in symptomatic postmenopausal women, especially regarding sexual function. Tibolone mainly improved sexual function, while LD-HT was more effective than tibolone or calcium/vitamin D3 for vasomotor symptoms.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

11.

Does hormone therapy improve age-related skin changes in postmenopausal women? A randomized, double-blind, double-dummy, placebo-controlled multicenter study assessing the effects of norethindrone acetate and ethinyl estradiol in the improvement of mild to moderate age-related skin changes in postmenopausal women.

Author: PhillipsTania J, SymonsJames, MenonSandeep,

Low-dose hormone therapy for 48 weeks in postmenopausal women does not significantly alter mild to moderate age-related facial skin changes.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

12.

Effects of low-dose norethindrone acetate plus ethinyl estradiol (0.5 mg/2.5 microg) in women with postmenopausal symptoms: updated analysis of three randomized, controlled trials.

Author: RowanJean P, SimonJames A, SperoffLeon, EllmanHerman

Vasomotor symptom relief

This analysis assessed the efficacy of a low-dose combination of norethindrone acetate and ethinyl estradiol for menopausal symptoms, adhering to conservative FDA guidelines. The analysis aimed to further evaluate the efficacy of this combination in women with more frequent and intense vasomotor symptoms than previously studied.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.

Language : English

13.

Oral hormone therapy with 17beta-estradiol and 17beta-estradiol in combination with norethindrone acetate in the prevention of bone loss in early postmenopausal women: dose-dependent effects.

Author: GreenwaldMaria W, GluckOscar S, LangEva, RakovViatcheslav

Bone loss prevention

A 2-year multicenter, double-blind, randomized, placebo-controlled study examined the efficacy and safety of different doses of 17beta-estradiol (E(2)) alone and continuous-combined oral formulations of E(2) and norethindrone acetate (NETA) versus placebo in the prevention of bone loss in newly menopausal women.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

14.

Interaction of St. John's Wort with oral contraceptives: effects on the pharmacokinetics of norethindrone and ethinyl estradiol, ovarian activity and breakthrough bleeding.

Author: MurphyPatricia A, KernSteven E, StanczykFrank Z, WesthoffCarolyn L

Breakthrough bleeding
Contraceptive effectiveness
Ovulation

St. John's Wort is associated with increased metabolism of norethindrone and ethinyl estradiol, breakthrough bleeding, follicle growth and ovulation. Women using OCs should be cautioned that St. John's Wort might interfere with contraceptive effectiveness.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Controlled Clinical TrialA clinical trial that evaluates the effectiveness of a treatment by comparing a group that receives the intervention with a group that receives a placebo or standard treatment.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

16.

Effects of levonorgestrel, medroxyprogesterone acetate, norethindrone, and 17beta-estradiol on vascular endothelial growth factor isomers 121 and 165 in Ishikawa cells.

Author: ArcherDavid F, NavarroFrancisco J, LeslieSusan, MirkinSebastian

Irregular bleeding

Estradiol and progestins increased the expression of vascular endothelial growth factor (VEGF) isoforms 121 and 165 in Ishikawa cells in vitro.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

17.

A randomized, double-blind, placebo-controlled, multicenter study that assessed the endometrial effects of norethindrone acetate plus ethinyl estradiol versus ethinyl estradiol alone.

Author: PortmanDavid J, SymonsJames P, WilbornWalter, KempfertNona J

Endometrial protection

Norethindrone acetate effectively protects the endometrium from estrogen-induced hyperplasia. Norethindrone acetate/ethinyl estradiol combinations also significantly reduce endometrial proliferation compared to conjugated equine estrogens/medroxyprogesterone acetate.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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