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Endocrine Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
As with the other progestogenic agents described in this section, norethisterone works by mimicking the action of progesterone itself. It is an agonist of the progesterone receptor but also has weak androgenic and estrogenic activity mostly at high doses, with no other significant hormonal activity. In the UK norethisterone is recommended by NICE for the treatment of breast cancer, endometriosis, dysfunctional uterine bleeding (e.g., menorrhagia), dysmenorrhea, postponement of menstruation, and contraception purposes.
Monographs of Topical Drugs that Have Caused Contact Allergy/Allergic Contact Dermatitis
Published in Anton C. de Groot, Monographs in Contact Allergy, 2021
Norethisterone is a synthetic progestational hormone with actions similar to those of progesterone but functioning as a more potent inhibitor of ovulation. It has weak estrogenic and androgenic properties. The hormone has been used in treating amenorrhea, functional uterine bleeding, endometriosis, and for contraception. In pharmaceutical products, norethisterone is employed as norethisterone acetate (CAS number 51-98-9, EC number 200-132-0, molecular formula C22H28O3) (1).
DRCOG MCQs for Circuit C Answers
Published in Una F. Coales, DRCOG: Practice MCQs and OSCEs: How to Pass First Time three Complete MCQ Practice Exams (180 MCQs) Three Complete OSCE Practice Papers (60 Questions) Detailed Answers and Tips, 2020
All the above are acceptable methods of treatment for endometriosis. Danazol inhibits pituitary gonadotrophin secretion and at 800 mg daily for 6 months suppresses menstruation. Androgenic side-effects include acne, hirsutism, voice deepening (irreversible) and weight gain. Norethisterone, at 10-15 mg daily starting on day 5 for 4-6 months, is also an acceptable progestogen form of therapy for suppression of menstruation. Side effects include nausea, vomiting, weight gain and fluid retention. Surgical methods include diathermy or local excision of the endometriotic tissue or total hysterectomy and BSO.
Novel pharmacological therapies for the treatment of endometriosis
Published in Expert Review of Clinical Pharmacology, 2022
Laura Buggio, Dhouha Dridi, Giussy Barbara, Camilla E.M. Merli, Giulia Emily Cetera, Paolo Vercellini
In June 2022, two replicate phase 3, multicentre, randomized, double-blind, placebo-controlled studies (namely, SPIRIT 1 and 2) evaluated the efficacy and safety of relugolix combination therapy (relugolix 40 mg, estradiol 1 mg, norethisterone acetate 0.5 mg) in the management of endometriosis-associated pain [27]. Subjects were divided into three groups: placebo, relugolix combination therapy, or delayed relugolix combination therapy (relugolix 40 mg alone in the first 12 weeks followed by relugolix combination therapy in the following 12 weeks). A total of 1261 women were recruited (n = 638 SPIRIT 1 and n = 623 SPIRIT 2). The co-primary endpoints in both studies were the proportions of responders at the end of the treatment period in terms of dysmenorrhea and non-menstrual pelvic pain relief. The dysmenorrhea responder rate was substantially higher in the relugolix combination therapy arms than in the placebo arm (75% vs 27% in SPIRIT 1 and 75% vs 30% in SPIRIT 2, both P < 0.0001). The differences in the non-menstrual pelvic pain responder rate between the relugolix combination therapy arms and the placebo arm were slightly smaller (59% vs 40% in SPIRIT 1 and 66% vs 43% in SPIRIT 2, both P < 0.0001). In patients treated with relugolix combination therapy, mean percentage changes in lumbar spine and total hip BMD from baseline to week 12 and 24 were less than 1% in both studies. In the delayed relugolix combination therapy group lumbar spine and total hip BMD substantially declined in the first 12 weeks (relugolix monotherapy) and remained stable during the transition to relugolix combined therapy.
Current approaches to overcome the side effects of GnRH analogs in the treatment of patients with uterine fibroids
Published in Expert Opinion on Drug Safety, 2022
Mohamed Ali, Mohamed Raslan, Michał Ciebiera, Kornelia Zaręba, Ayman Al-Hendy
A scientific working group advocated for the use of suitable add-back therapy in conjunction with GnRH agonist treatment to ameliorate hypoestrogenic symptoms, prevent precancerous endometrial changes and perhaps prolong the duration of medication beyond 6 months while maintaining therapeutic efficacy [58,59]. Earlier and following the results of randomized controlled trials in women with endometriosis, the FDA approved progestin NETA, also known as norethisterone acetate, at a daily dose of 5 mg in combination with a synthetic GnRH agonist (leuprolide acetate), as an add-back therapy in women with endometriosis. NETA has profound tissue-specific progestogenic, estrogenic or antiestrogenic, and androgenic actions, where the average conversion ratio of NETA to ethynyl estradiol (E2) by aromatization is 0.7% to 1% at 5 mg NETA dosages. It is believed that the estrogenic action of NETA may explain its beneficial effect on BMD. Low dosages of E2 1 mg coupled with NETA 0.5 mg have been shown to prevent bone loss in endometriosis patients receiving GnRH agonist treatment [60]. Consequently, this combination is being used for women with UFs who are on long-term GnRH antagonist therapy.
Effects of progestogens used in menopause hormone therapy on the normal breast and benign breast disease in postmenopausal women
Published in Climacteric, 2021
C. Rueda Beltz, A. Rojas Figueroa, S. Hinestroza Antolinez, A. Bastidas
Within the benign histological changes evidenced in the breast, cell proliferation without and with atypia is the main reported finding. Conner et al. analyzed a sample of 50 postmenopausal women on MHT composed of estradiol valerate (2 mg per day) combined with dienogest (2 mg per day) or norethisterone acetate (1 mg per day) and performed a breast biopsy at 3 and 6 months of treatment (135 fine-needle aspiration biopsies in total), measuring an immunohistochemical marker indicative of cell proliferation (Ki-67/MIB-1, a monoclonal antibody that reacts with human nuclear antigen)27. Both progestogens showed a three-fold to four-fold increased risk of cell division (MIB-1 positive: 6.8% in group 1 vs. 9% in group 2 at 6 months), without significant difference between them27. Of utmost importance for the analysis of these conclusions is the fact that 34% of the biopsies were not analyzed due to low cell counts and that five of the patients included in the trial discontinued the intervention treatment and were included in the analysis27. However, the question that arises after considering these results is which of the combined MHT components, estrogenic or progestogen (dienogest and norethisterone acetate), had a stronger effect on the onset of cell proliferation. Similar results in mammary proliferation with norethisterone have been described by Conner et al.28, demonstrated by an increased Ki-67/MIB-1 percentage.