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Fertility and Sterility Mar 2017For decades, combined estrogen-progestin oral contraceptive pills (OCPs) have been the first-line treatment for menstrual and pelvic pain associated with endometriosis... (Review)
Review
For decades, combined estrogen-progestin oral contraceptive pills (OCPs) have been the first-line treatment for menstrual and pelvic pain associated with endometriosis without any clinical evidence of efficacy. Initial relief provided by OCPs is likely a result of improvement in primary dysmenorrhea. Biologic data and limited clinical evidence support a potential adverse effect of long-term use of OCPs on the progression of endometriosis. In contrast, there is randomized, controlled trial data to support the use of oral progestin-only treatment for pelvic pain associated with endometriosis and for suppressing the anatomic extent of endometriotic lesions. Both norethindrone acetate and dienogest have regulatory approval for treating endometriosis and may be better than OCPs as a first-line therapy.
Topics: Administration, Oral; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Endometriosis; Endometrium; Female; Humans; Menstrual Cycle; Nandrolone; Norethindrone; Norethindrone Acetate; Pelvic Pain; Progestins; Treatment Outcome
PubMed: 28162779
DOI: 10.1016/j.fertnstert.2017.01.003 -
Drugs Oct 2022An oral fixed-dose combination of relugolix/estradiol/norethisterone (also known as norethindrone) acetate (Ryeqo; Myfembree) has been approved for the management of... (Review)
Review
An oral fixed-dose combination of relugolix/estradiol/norethisterone (also known as norethindrone) acetate (Ryeqo; Myfembree) has been approved for the management of heavy menstrual bleeding associated with uterine fibroids in the USA and management of moderate to severe symptoms of uterine fibroids in the EU. Relugolix is a gonadotropin releasing hormone (GnRH) receptor antagonist that decreases serum estradiol and progesterone concentrations to postmenopausal levels. The addition of estradiol/norethisterone acetate to relugolix ameliorates relugolix-induced bone loss and hot flush. In the two phase 3 LIBERTY trials, relugolix + estradiol/norethisterone substantially decreased menstrual bleeding and improved a range of other uterine fibroid symptoms in women with uterine fibroids-associated heavy menstrual bleeding. The combination was generally well tolerated, with vasomotor symptoms being the most common adverse reaction. Treatment with this combination for over up to 2 years did not induce a clinically meaningful bone loss in the majority of women. Relugolix/estradiol/norethisterone acetate, with its convenient once-daily administration, is a useful addition to current pharmacological treatment options for premenopausal women with symptomatic uterine fibroids.
Topics: Female; Humans; Norethindrone Acetate; Menorrhagia; Uterine Neoplasms; Leiomyoma; Norethindrone; Estradiol; Acetates
PubMed: 36331779
DOI: 10.1007/s40265-022-01790-4 -
Obstetrics and Gynecology Sep 2022To evaluate associations between use of seven progestogens and incident acute venous thromboembolism (VTE) among women of reproductive age.
OBJECTIVE
To evaluate associations between use of seven progestogens and incident acute venous thromboembolism (VTE) among women of reproductive age.
METHODS
This nested matched case-control study identified women aged 15-49 years from January 1, 2010, through October 8, 2018, in the IBM MarketScan databases, a nationwide sample of private insurance claims in the United States. After exclusions, 21,405 women with incident acute VTE (case group), identified by diagnosis codes, were matched 1:5 by year of birth and index date through risk set sampling to 107,025 women without prior VTE (control group). From lowest to highest systemic dose based on a modified hierarchy, progestogens studied were levonorgestrel-releasing intrauterine device (LNG-IUD), oral norethindrone, etonogestrel implant, oral progesterone, oral medroxyprogesterone acetate, oral norethindrone acetate, and depot medroxyprogesterone acetate (DMPA). Conditional logistic regression models adjusted for 16 VTE risk factors were used to estimate odds ratios and 99% CIs for incident acute VTE associated with current progestogen use compared with nonuse. The primary analysis treated each progestogen as a binary exposure. Dose, which varied for oral formulations, and chronicity were explored separately. Significance was set at P <.01 to allow for multiple comparisons.
RESULTS
Current use of higher-dose progestogens was significantly associated with increased odds of VTE compared with nonuse (oral norethindrone acetate: adjusted odds ratio [aOR] 3.00, 99% CI 1.96-4.59; DMPA: aOR 2.37, 99% CI 1.95-2.88; and oral medroxyprogesterone acetate: aOR 1.98, 99% CI 1.41-2.80). Current use of other progestogens was not significantly different from nonuse (LNG-IUD, etonogestrel implant, and oral progesterone) or had reduced odds of VTE (oral norethindrone). Sensitivity analyses that assessed misclassification bias supported the primary findings.
CONCLUSION
Among reproductive-aged women using one of seven progestogens, only use of norethindrone acetate and medroxyprogesterone acetate-considered higher-dose progestogens-was significantly associated with increased odds of incident acute VTE. The roles of progestogen type, dose, and indication for use warrant further study.
Topics: Adult; Female; Humans; Case-Control Studies; Intrauterine Devices, Medicated; Levonorgestrel; Medroxyprogesterone Acetate; Norethindrone; Norethindrone Acetate; Progesterone; Progestins; Venous Thromboembolism
PubMed: 35926206
DOI: 10.1097/AOG.0000000000004896 -
The New England Journal of Medicine Dec 2005Oral contraceptives are rarely prescribed for women with systemic lupus erythematosus, because of concern about potential negative side effects. In this double-blind,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Oral contraceptives are rarely prescribed for women with systemic lupus erythematosus, because of concern about potential negative side effects. In this double-blind, randomized, noninferiority trial, we prospectively evaluated the effect of oral contraceptives on lupus activity in premenopausal women with systemic lupus erythematosus.
METHODS
A total of 183 women with inactive (76 percent) or stable active (24 percent) systemic lupus erythematosus at 15 U.S. sites were randomly assigned to receive either oral contraceptives (triphasic ethinyl estradiol at a dose of 35 microg plus norethindrone at a dose of 0.5 to 1 mg for 12 cycles of 28 days each; 91 women) or placebo (92 women) and were evaluated at months 1, 2, 3, 6, 9, and 12. Subjects were excluded if they had moderate or high levels of anticardiolipin antibodies, lupus anticoagulant, or a history of thrombosis.
RESULTS
The primary end point, a severe lupus flare, occurred in 7 of 91 subjects receiving oral contraceptives (7.7 percent) as compared with 7 of 92 subjects receiving placebo (7.6 percent). The 12-month rates of severe flare were similar: 0.084 for the group receiving oral contraceptives and 0.087 for the placebo group (P=0.95; upper limit of the one-sided 95 percent confidence interval for this difference, 0.069, which is within the prespecified 9 percent margin for noninferiority). Rates of mild or moderate flares were 1.40 flares per person-year for subjects receiving oral contraceptives and 1.44 flares per person-year for subjects receiving placebo (relative risk, 0.98; P=0.86). In the group that was randomized to receive oral contraceptives, there was one deep venous thrombosis and one clotted graft; in the placebo group, there was one deep venous thrombosis, one ocular thrombosis, one superficial thrombophlebitis, and one death (after cessation of the trial).
CONCLUSIONS
Our study indicates that oral contraceptives do not increase the risk of flare among women with systemic lupus erythematosus whose disease is stable.
Topics: Adolescent; Adult; Contraceptives, Oral, Combined; Double-Blind Method; Ethinyl Estradiol; Female; Humans; Lupus Erythematosus, Systemic; Norethindrone; Pregnancy; Severity of Illness Index
PubMed: 16354891
DOI: 10.1056/NEJMoa051135 -
Women's Health (London, England) Jan 2016Women with benign heavy menstrual bleeding have the choice of a number of medical treatment options to reduce their blood loss and improve quality of life. The role of... (Review)
Review
Women with benign heavy menstrual bleeding have the choice of a number of medical treatment options to reduce their blood loss and improve quality of life. The role of the clinician is to provide information to facilitate women in making an appropriate choice. Unfortunately, many options can be associated with hormonal side effects, prevention of fertility and lack of efficacy, leading to discontinuation and progression to surgical interventions. Herein, we discuss the various options currently available to women, including antifibrinolytics, nonsteroidal anti-inflammatory preparations, oral contraceptive pills and oral, injectable and intrauterine progestogens. In addition, we describe the more novel option of selective progesterone receptor modulators and their current benefits and limitations.
Topics: Antifibrinolytic Agents; Contraceptives, Oral, Hormonal; Female; Humans; Intrauterine Devices, Medicated; Levonorgestrel; Medroxyprogesterone; Menorrhagia; Norethindrone; Progesterone; Quality of Life; Women's Health
PubMed: 26695687
DOI: 10.2217/whe.15.100 -
Proceedings of the Royal Society of... Feb 1973
Topics: Adolescent; Adult; Age Factors; Aged; Blood Pressure; Castration; Climacteric; Endometrial Hyperplasia; Estradiol; Estrogens; Estrogens, Conjugated (USP); Female; Humans; Hysterectomy; Libido; Male; Medroxyprogesterone; Menopause; Methyltestosterone; Middle Aged; Norethindrone; Osteoporosis; Progesterone
PubMed: 4351701
DOI: No ID Found -
BMJ Sexual & Reproductive Health Apr 2021Progestogens (progestins) are widely used for contraception, in postmenopausal hormone therapy, and in treatment of abnormal uterine bleeding and endometriosis.... (Review)
Review
INTRODUCTION
Progestogens (progestins) are widely used for contraception, in postmenopausal hormone therapy, and in treatment of abnormal uterine bleeding and endometriosis. Norethisterone (NET) and its acetate (NETA) differ from other progestogens by their partial conversion to ethinylestradiol (EE). We review their special characteristics and focus on the clinically relevant risk factors associated with estrogen action, such as migraine with aura and risk of thrombosis.
METHODS
Narrative review based on a medical literature (OvidMedline and PubMed) search.
RESULTS
NET converts to significant amounts of EE; 10-20 mg NET corresponds to 20-30 µg EE. The effects of NET on the endometrium are pronounced, making it a good choice for treating abnormal uterine bleeding, endometriosis, and endometrial hyperplasia. NET also has beneficial effects on bone mineral density and positive or neutral effects on cardiovascular health. Conversely, long-term use of NET is associated with a slightly increased breast cancer risk, and the risk of venous thromboembolism is moderately increased. This risk seems to be dose-dependent; contraceptive use carries no risk, but therapeutic doses might be associated with an increased risk. Studies suggest an association between combinations of EE and progestogens and ischaemic stroke, which in particular concerns women with migraine. No studies have, however, assessed this risk related to the therapeutic use of NET.
CONCLUSIONS
NET is a potent progestogen, especially when considering the endometrium. Its partial conversion to EE, however, is important to remember. Clinical consideration is required with women at high risk for either breast cancer or thromboembolism, or experiencing migraine with aura.
Topics: Biological Factors; Breast Neoplasms; Contraceptive Agents, Hormonal; Endometrium; Female; Humans; Norethindrone; Norethindrone Acetate; Thrombosis
PubMed: 32398290
DOI: 10.1136/bmjsrh-2020-200619 -
Journal of Pediatric Endocrinology &... Aug 2023We sought to study factors predictive of achieving menstrual suppression with norethindrone vs. norethindrone acetate in adolescents, as optimal dosing is unknown....
OBJECTIVES
We sought to study factors predictive of achieving menstrual suppression with norethindrone vs. norethindrone acetate in adolescents, as optimal dosing is unknown. Secondary outcomes included analyzing prescriber practices and patient satisfaction.
METHODS
We performed a retrospective chart review of adolescents ages <18 years presenting to an academic medical center from 2010 to 2022. Data collected included demographics, menstrual history, and norethindrone and norethindrone acetate use. Follow-up was measured at one, three, and 12 months. Main outcome measures were starting norethindrone 0.35 mg, continuing norethindrone 0.35 mg, achieving menstrual suppression, and patient satisfaction. Analysis included Chi-square and multivariate logistic regression.
RESULTS
Of 262 adolescents initiating norethindrone or norethindrone acetate, 219 completed ≥1 follow-up. Providers less often started norethindrone 0.35 mg for patients with body mass index ≥25 kg/m, prolonged bleeding, or younger age at menarche, but more often for patients who were younger, had migraines with aura, or were at risk of venous thromboembolism. Those with prolonged bleeding or older age at menarche were less likely to continue norethindrone 0.35 mg. Obesity, heavy menstrual bleeding, and younger age were negatively associated with achieving menstrual suppression. Patients with disabilities reported greater satisfaction.
CONCLUSIONS
While younger patients more often received norethindrone 0.35 mg vs. norethindrone acetate, they were less likely to achieve menstrual suppression. Patients with obesity or heavy menstrual bleeding may achieve suppression with higher doses of norethindrone acetate. These results reveal opportunities to improve norethindrone and norethindrone acetate prescribing practices for adolescent menstrual suppression.
Topics: Female; Adolescent; Humans; Norethindrone; Menorrhagia; Norethindrone Acetate; Retrospective Studies; Obesity
PubMed: 37279406
DOI: 10.1515/jpem-2023-0133 -
British Medical Journal May 1971
Topics: Candidiasis, Vulvovaginal; Contraceptives, Oral; Dyspareunia; Female; Humans; Libido; Norethindrone
PubMed: 5572399
DOI: 10.1136/bmj.2.5756.277-c