Norethindrone Acetate in the Medical Management of Adenomyosis

Muneyyirci-Delale, Ozgul; Chandrareddy, Ashadeep; Mankame, Siddhi; Osei-Tutu, N.; Gizycki, Hans von

doi:10.3390/ph5101120

Cited by 22 publications

(14 citation statements)

References 26 publications

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“…The definitive treatment and diagnosis of adenomyosis is hysterectomy and pathological examination of extirpated uterus. However, conservative management such as norethindrone acetate, levonorgestrol impregnated IUD (mirena), estrogen, danazol, GnRH agonists, resection of lesions, hysteroscopic endometrial ablation, uterine artery embolization (UAE) and magnetic resonance guided focused ultrasound surgery (MRgFUS) can be employed [24,25].…”

Section: Resultsmentioning

confidence: 99%

Association between etiopathogenesis of morbidly adherent placenta and adenomyosis

Enakpene¹,

Muneyyirci-Delale²

2012

OJOG

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The association between etio-pathogenesis of morbidly adherent placenta (MAP) or placenta cretas and adenomyosis has never been described in medical literature. Contrary to the believe that MAP is due to direct invasion of trophoblastic tissues into the adjacent normal myometrium due to prior uterine surgeries, this article describes how pre-existence of adenomyosis acts as a precursor for the development of placenta cretas. It elucidates how prior uterine traumas such as surgeries, repeated childbirths and endometritis cause endometrial tissues to invade the myometrium as a result of disruption of decidua basalis. The invaded endometrial tissues cause hyper-plasia and hypertrophy of surrounding myometrium to form the clinical entity called adenomyosis. The over-expression of bcl-2 oncogene in the endometrium causes inhibition of apoptosis of endometrial cells removing the barrier of trophoblastic tissues to invade the myometrium to form MAP. This hypothesis is based on the similarity of their clinical perspectives, similar pathological description of the two disease entities and their common molecular components. Both diseases increase with age; more in women older than 35 years and also in those with history of previous endometrial traumas such as surgeries, childbirth and endometritis. Both diseases also share common pathological factors and molecular components due to absence of deciduas basalis and over-expression of bcl-2 oncoprotein gene, inhibition of cell apoptosis and failure to find genetic abnormalities such as mutations of K-ras, P53 or LOH. An ongoing study looking at uterine specimens from cesarean hysterectomies and pelvic MRI evaluation of patients with retained placentas to prove that pre-existing adenomyosis may be a precursor to the development of morbidly adherent placenta is near to conclusion

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Section: Resultsmentioning

confidence: 99%

Association between etiopathogenesis of morbidly adherent placenta and adenomyosis

Enakpene¹,

Muneyyirci-Delale²

2012

OJOG

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“…15 Only one study has evaluated oral norethindrone acetate (5 mg daily), approved by the Food and Drug Administration (FDA) for the treatment of endometriosis, and found improvement in menstrual bleeding in women with adenomyosis by patientreported bleeding scores, which quantified the number of bleeding days by heaviness of bleeding. 16 Painful menses, assessed by VAS, is improved by the use of COC; however, LNG-IUS is more well studied and in one RCT by Shaaban et al, it was noted to be superior to COC. 9 LNG-IUS showed both initial and prolonged (12-60 months) improvements in VAS scores.…”

Section: Contraceptive Steroidsmentioning

confidence: 99%

“…[18][19][20] Notably, norethindrone acetate, another 19-norsteroid that is available in the United States, taken for 3 weeks followed by 1 week without medication showed improvement in patient-reported pain scores. 16…”

Section: Contraceptive Steroidsmentioning

confidence: 99%

Current and Future Medical Therapies for Adenomyosis

Cope

Stewart

2020

Semin Reprod Med

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There is no approved medical therapy for adenomyosis and limited evidence to guide treatments in part due to the complexity of nonhistologic diagnosis and the prevalence of concomitant gynecologic conditions. Most available evidence focuses on the treatment of heavy menstrual bleeding, painful menses, and pelvic pain. Data evaluating fertility outcomes, sexual function, and quality of life following treatment are lacking. Additionally, there is no disease-specific measure of quality of life for adenomyosis. The levonorgestrel-releasing intrauterine system appears to be the most effective first-line therapy based on efficacy compared with oral agents, maintenance of steady-state hormonal levels, and contraceptive benefit. In areas where it is marketed, the progestin dienogest appears superior to combined oral contraceptives. Long-acting gonadotropin-releasing hormone agonists are effective and should be considered second-line therapy but are limited by hypogonadal effects. Additional data regarding oral gonadotropin-releasing hormone antagonists are required. While aromatase inhibitors demonstrate improvement in heavy menstrual bleeding and pelvic pain, further research is needed to determine their role in the management of adenomyosis. Progesterone receptor modulators may have a role for this disease if released again to market with appropriate safety parameters. Finally, modulation of prolactin and/or oxytocin may provide novel nonsteroidal treatment options.

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“…Because these esters act as prodrugs, they are cleaved into active compounds upon biotransformation. The public information of Aygestin ® (NETA tablets, USP), a drug that has been approved by the United States Food and Drug Administration (Muneyyirci-Delale et al, 2012), illustrates that NETA is twice as potent as NET on a weight basis. The long-term efficacy of NETA has also been repeatedly demonstrated (Muneyyirci-Delale and Jalou, 2001;Ferrero et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Probing the binding of two 19‐nortestosterone derivatives to human serum albumin: insights into the interactions of steroid hormone drugs with functional biomacromolecule

Wang

et al. 2016

J of Molecular Recognition

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Norethindrone acetate (NETA) is a fatty acid ester of norethindrone (NET) that can convert to its more active parent compound NET when orally administered. To study the interactions of NETA and NET with human serum albumin (HSA), we applied fluorescence spectroscopy, circular dichroism (CD), and molecular docking. The effects of metal ions on the HSA-NETA/NET system were also explored. Fluorescence data showed that the quenching mechanism of HSA by NETA and NET was consistent with a static model and that the binding constant of NETA was higher than that of NET. Thermodynamic parameters indicated that hydrogen bonds and van der Waals forces were the main forces maintaining the stability of the HSA-NETA/NET complex. Molecular modeling studies revealed that NETA and NET were bound within subdomain IIA of HSA, in accordance with the site probe results. Synchronous fluorescence spectroscopy, CD, and three-dimensional fluorescence spectroscopy further confirmed that the binding of NETA/NET to HSA changed the secondary structure of the protein. All other metal ions, except for Ca(2+) , decreased the K value of the HSA-NETA/NET system with enhancement of the maximum effectiveness of NETA/NET. Three commercially available steroid hormone drugs influenced the binding ability of NETA on HSA to different extents. This study provides novel insights into the interactions between HSA and NETA/NET, as well as a solid foundation for future research on drug pharmacokinetics and pharmacodynamics. Copyright © 2016 John Wiley & Sons, Ltd.

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Norethindrone Acetate in the Medical Management of Adenomyosis

Cited by 22 publications

References 26 publications

Association between etiopathogenesis of morbidly adherent placenta and adenomyosis

Association between etiopathogenesis of morbidly adherent placenta and adenomyosis

Current and Future Medical Therapies for Adenomyosis

Probing the binding of two 19‐nortestosterone derivatives to human serum albumin: insights into the interactions of steroid hormone drugs with functional biomacromolecule

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