Side Effects of norethindrone: A Synthesis of Findings from 22 Studies

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Original Abstract of the Article

Major Research Findings

Norethindrone is a synthetic progestin often used to treat gynecological conditions such as endometriosis, uterine fibroids, and dysmenorrhea. Numerous studies have demonstrated norethindrone's effectiveness in alleviating these conditions' symptoms. 17 , 13 , 4 . However, it's important to note that norethindrone can also have side effects. Common side effects include irregular bleeding, weight gain, decreased libido, and headaches. 17 , 13 . These side effects are believed to be related to norethindrone's impact on the body's hormonal balance.

Reasons for Side Effects

Norethindrone, a synthetic progestin, works by altering the body's balance of female hormones. This change in hormonal balance is thought to be the primary cause of side effects such as irregular bleeding, weight gain, decreased libido, and headaches.

Common Side Effects

Irregular Bleeding

Norethindrone can lead to irregular bleeding. 17 , 13 . This occurs because norethindrone can affect the thickness of the uterine lining.

Weight Gain

Weight gain is a potential side effect of norethindrone. 17 . This can be attributed to norethindrone's influence on appetite and metabolism.

Decreased Libido

Norethindrone can result in decreased libido. 17 . This is likely due to the impact of norethindrone on the balance of sex hormones in the body.

Headaches

Headaches are another possible side effect of norethindrone. 17 . This is believed to be caused by norethindrone's effect on blood vessels, causing vasoconstriction.

Mood Swings

Norethindrone can contribute to mood swings. 19 . This is likely due to norethindrone's influence on neurotransmitters in the brain.

Nausea and Vomiting

Nausea and vomiting are potential side effects of norethindrone. 19 . This is believed to be caused by the impact of norethindrone on the digestive system.

Countermeasures for Side Effects

Irregular Bleeding

If you are experiencing irregular bleeding, it's essential to consult your doctor. They can determine the cause of the bleeding and recommend the appropriate course of treatment.

Weight Gain

If weight gain is a concern, talk to your doctor. They can help identify the underlying cause of the weight gain and recommend appropriate measures. Lifestyle modifications, such as dietary changes and exercise, may be beneficial.

Decreased Libido

If you're experiencing a decrease in libido, consulting with your doctor is recommended. They can help determine the cause of the decreased libido and recommend appropriate treatment.

Headaches

If you are experiencing headaches, it's advisable to seek medical advice. Your doctor can identify the cause of the headaches and recommend appropriate treatment. If over-the-counter pain relievers don't provide relief, a doctor's consultation is necessary.

Mood Swings

If mood swings are a concern, seeking help from a healthcare professional is recommended. They can identify the cause of the mood swings and recommend appropriate treatment. Counseling or psychotherapy may be helpful in managing mood swings.

Nausea and Vomiting

If you are experiencing nausea and vomiting, consult your doctor. They can identify the cause of these symptoms and recommend appropriate treatment.

Comparison Across Studies

Commonalities in Studies

A consistent finding across numerous studies is that norethindrone can lead to side effects such as irregular bleeding, weight gain, decreased libido, and headaches. 17 , 13 .

Differences in Studies

The frequency and severity of side effects can vary depending on the specific study. This variability may be attributed to factors such as the age of the study participants, the type of condition being treated, and the dosage of norethindrone.

Points to Note When Applying to Real Life

Norethindrone is an effective medication for treating various gynecological conditions, but it's crucial to acknowledge the potential for side effects. Before starting norethindrone, consulting with your doctor to discuss the risks and benefits is essential.

Limitations of Current Research

The current body of research on the side effects of norethindrone is not yet exhaustive. Further research is needed to gain a more comprehensive understanding of these side effects.

Future Research Directions

Developing new treatment approaches that minimize the side effects of norethindrone is a significant area for future research. Additionally, elucidating the mechanisms underlying norethindrone's side effects is crucial for developing safer and more effective medications.

Conclusion

Norethindrone is a valuable medication for treating gynecological conditions, but it's important to be aware of the potential for side effects. Before starting norethindrone, a conversation with your doctor to discuss the risks and benefits is highly recommended. Future research aimed at developing new treatments that minimize side effects and a better understanding of the mechanisms involved in norethindrone's side effects are eagerly anticipated.

Literature analysis of 22 papers
Positive Content
20
Neutral Content
1
Negative Content
1
Article Type
5
1
1
4
21
1.

Oral Gonadotropin-Releasing Hormone Antagonists for the Treatment of Uterine Leiomyomas.

Author: NeblettMichael F, StewartElizabeth A

Amenorrhea
Anemia improvement
Leiomyoma bleeding reduction
Leiomyoma pain reduction
Reduced hypogonadal side effects
Uterine volume reduction
Hypogonadal side effects

This overview reviews the efficacy and safety of oral gonadotropin-releasing hormone (GnRH) antagonists for the management of uterine leiomyomas. Oral GnRH antagonists provide rapid suppression of sex steroids and can reduce leiomyoma-associated heavy menstrual bleeding, pain, and anemia.

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

2.

Differential off-target glucocorticoid activity of progestins used in endocrine therapy.

Author: KomaneMaleshigo, AvenantChanel, Louw-du ToitRenate, AfricanderDonita J, HapgoodJanet P

Contraception
Endocrine therapy
Side effects

This study compared the glucocorticoid receptor (GR) activity of several progestins commonly used in endocrine therapy. The results suggest that MPA is likely to have GR-mediated side effects, while ETG and NES may have selective effects, and LNG and NET are unlikely to have significant GR activity.

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.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

4.

Elagolix treatment in women with heavy menstrual bleeding associated with uterine fibroid: a systematic review and meta-analysis.

Author: MuhammadJuliawati, YusofYusnita, AhmadImran, NorhayatiMohd Noor

Menorrhagia treatment
Hypoestrogenism

This systematic review and meta-analysis evaluated the effectiveness of elagolix for treating menorrhagia in women with uterine fibroids. Elagolix was effective compared to placebo, and the addition of estradiol/norethindrone acetate mitigated the hypoestrogenism associated with elagolix.

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.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

5.

Association of Hormonal Contraceptive Use With Adverse Health Outcomes: An Umbrella Review of Meta-analyses of Randomized Clinical Trials and Cohort Studies.

Author: BrabaharanSharmila, VeettilSajesh K, KaiserJennifer E, Raja RaoVrosha Rau, WattanayingcharoenchaiRujira, MaharajanMarikannan, InsinPutsarat, TalungchitPattarawalai, AnothaisintaweeThunyarat, ThakkinstianAmmarin, ChaiyakunaprukNathorn

Hormonal contraception
Cancer risk
Cardiovascular risk

This umbrella review found that the associations between hormonal contraceptive use and adverse health outcomes were not supported by high-quality evidence. The review included 13 meta-analyses of randomized controlled trials (RCTs) and 45 meta-analyses of cohort studies. Of the 60 associations described in meta-analyses of RCTs, 14 were nominally statistically significant (P ≤ .05). Of the 96 associations described in meta-analyses of cohort studies, 40 were nominally statistically significant.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

6.

Current approaches to overcome the side effects of GnRH analogs in the treatment of patients with uterine fibroids.

Author: AliMohamed, RaslanMohamed, CiebieraMichał, ZarębaKornelia, Al-HendyAyman

Uterine fibroid treatment

Uterine fibroids are common and costly. There is a need for noninvasive treatments for uterine fibroids.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

8.

The Use of Norethisterone for the Treatment of Severe Uterine Bleeding in Adolescents: An Audit of Our Experience.

Author: PapapanagiotouIoannis K, CharamantaMaria, RoidiStella, Al-AchmarNikolaos Samer, SoldatouAlexandra, MichalaLina

Effective AUB treatment
Safe for adolescents
Minor side effects

Norethisterone (NET) is an effective and reliable treatment option for abnormal uterine bleeding (AUB) in adolescents. In this study, bleeding stopped within 46.1 hours of NET administration, with no serious adverse events reported.

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

Language : English

9.

Dienogest or Norethindrone acetate for the treatment of ovarian endometriomas: Can we avoid surgery?

Author: Del FornoSimona, MabroukMohamed, ArenaAlessandro, MattioliGiulia, GiaquintoIlaria, ParadisiRoberto, SeracchioliRenato

Reduced endometrioma size
Symptom relief
Uterine bleeding
Weight gain

Progestin therapy with dienogest (D) or norethindrone acetate (N) is effective in reducing the size of ovarian endometriomas and related symptoms, but dienogest appears to be more effective in relieving symptoms and better tolerated.

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.

Language : English

10.

Differential metabolism of clinically-relevant progestogens in cell lines and tissue: Implications for biological mechanisms.

Author: SkosanaSalndave B, WoodlandJohn G, CartwrightMeghan, EnfieldKim, KomaneMaleshigo, Louw-du ToitRenate, van der SpuyZephne, AvenantChanel, AfricanderDonita, StorbeckKarl-Heinz, HapgoodJanet P

Contraception
Hormonal replacement therapy

Progestogen metabolism is progestin- and cell line-specific. This may confound results of in vitro studies on progestogen mechanisms of action.

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.

Language : English

11.

Long-Term Effects of Gonadotropin-Releasing Hormone Agonists and Add-Back in Adolescent Endometriosis.

Author: GallagherJenny Sadler, MissmerStacey A, HornsteinMark D, LauferMarc R, GordonCatherine M, DiVastaAmy D

GnRHa efficacy
GnRHa side effects

Gonadotropin-releasing hormone agonist (GnRHa) with add-back therapy was effective for endometriosis pain in adolescents, but side effects were common, with almost half considered irreversible. Two-drug add-back regimens were more successful than standard add-back.

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.

Language : English

12.

Shifting from Oral Contraceptives to Norethisterone Acetate, or Vice Versa, because of Drug Intolerance: Does the Change Benefit Women with Endometriosis?

Author: VercelliniPaolo, OttoliniFederica, FrattaruoloMaria Pina, BuggioLaura, RobertoAnna, SomiglianaEdgardo

Improved tolerability
Side effects

This study investigated whether shifting from low-dose oral contraceptives (OC) to norethisterone acetate (NETA), or vice versa, improved tolerability in women with symptomatic endometriosis.

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

Language : English

13.

Is Shifting to a Progestin Worthwhile When Estrogen-Progestins Are Inefficacious for Endometriosis-Associated Pain?

Author: VercelliniPaolo, OttoliniFederica, FrattaruoloMaria Pina, BuggioLaura, RobertoAnna, SomiglianaEdgardo

Endometriosis treatment
Quality of life
Side effect risk

The study assessed the satisfaction of patients who switched from a low-dose oral contraceptive to norethisterone acetate for endometriosis. 70% of participants were satisfied with NETA treatment, and improvements were seen in health-related quality of life, psychological status, and sexual function.

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

16.

Evaluation of an ultra-low-dose oral contraceptive for dysmenorrhea: a placebo-controlled, double-blind, randomized trial.

Author: HaradaTasuku, MomoedaMikio

Relieved dysmenorrhea
Increased side effects

An ultra-low-dose oral contraceptive (NPC-01) was as effective as a standard dose (IKH-01) in relieving dysmenorrhea, but with a higher incidence of side effects. NPC-01 could represent a new option for long-term treatment of dysmenorrhea.

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.

Language : English

17.

Surgery versus hormonal therapy for deep endometriosis: is it a choice of the physician?

Author: BerlandaNicola, SomiglianaEdgardo, FrattaruoloMaria Pina, BuggioLaura, DridiDhouha, VercelliniPaolo

Endometriosis treatment
Pain relief
Anastomotic leakage
Decreased libido
Erratic bleeding
Headache
Rectovaginal fistula
Ureterovaginal fistula
Weight gain

This article provides an overview of the management of deep endometriosis, focusing on hormonal treatment and surgical excision. The article emphasizes the need for a personalized approach to treatment based on the patient's symptoms, priorities, and expectations.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

18.

Comparison of combined low-dose hormone therapy vs. tibolone in the prevention of bone loss.

Author: KalderM, KyvernitakisI, HarsO, KaukaA, HadjiP

HT improves bone density
Tibolone effective

This study compared the effects of two hormone therapies (HT) on bone mineral density (BMD) in postmenopausal women. After 2 years, low-dose combined HT (estradiol and norethisterone acetate) and tibolone showed similar effects on BMD at the lumbar spine, femoral neck, and total hip. QUS measurements also showed similar results.

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.

Language : English

19.

The Effects of Gonadotropin-Releasing Hormone Agonist Combined with Add-Back Therapy on Quality of Life for Adolescents with Endometriosis: A Randomized Controlled Trial.

Author: Sadler GallagherJenny, FeldmanHenry A, StokesNatalie A, LauferMarc R, HornsteinMark D, GordonCatherine M, DiVastaAmy D

Endometriosis treatment
Improved quality of life
Mood effects
Vasomotor effects

This study examines the impact of gonadotropin-releasing hormone agonists (GnRHa) on quality of life (QOL) in female adolescents with endometriosis, comparing an add-back regimen of norethindrone acetate (NA) with conjugated estrogens (CEE) to NA alone for preventing side effects.

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.

Language : English

20.

Depo-Provera Versus Norethisterone Acetate in Management of Endometrial Hyperplasia Without Atypia.

Author: NoohAhmed Mohamed, AbdeldayemHussein Mohammed, GirbashEhab F, ArafaEssa M, AtwaKhalid, Abdel-RaoufSamar M

Regression of EH
Side effects

Depo-Provera (medroxyprogesterone acetate) is an effective and safe treatment for endometrial hyperplasia without atypia. It is more effective than oral norethisterone acetate in achieving regression of nonatypical endometrial hyperplasia.

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.

Language : English

21.

Medical management of heavy menstrual bleeding.

Author: MaybinJacqueline A, CritchleyHilary O D

Menstrual bleeding reduction
Quality of life improvement
Hormonal side effects
Infertility
Lack of efficacy

This article discusses the various medical treatment options available for women with heavy menstrual bleeding, including their benefits and limitations.

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.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

22.

Effect of transdermal hormone therapy on platelet haemostasis in menopausal women.

Author: StachowiakGrzegorz, PertyńskiTomasz, Pertyńska-MarczewskaMagdalena

Improved platelet hemostasis

Transdermal hormone therapy (HT) in the form of combined, estrogen-progestogen patches positively modified platelet hemostasis in postmenopausal women. This therapy reversed the adverse effects that occur after menopause.

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

Language : English

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