Abstract
Objectives
To obtain more precise and detailed information regarding the bleeding patterns of
nomegestrol acetate (NOMAC)/17β-estradiol (E2) and drospirenone/ethinyl estradiol
(DRSP/EE) and to identify whether baseline demographic characteristics were associated
with unscheduled bleeding, absent scheduled bleeding, or amenorrhea.
Study design
This analysis pooled results from two pivotal open-label, randomized trials that compared
bleeding patterns of NOMAC/E2 and DRSP/EE. In the two studies 4317 women aged 18–50
years from 24 countries across the Americas, Europe, and Asia underwent treatment.
Results
2835 women taking NOMAC/E2 (2.5 mg/1.5 mg) in a 24/4-day regimen and 938 women taking
DRSP/EE (3 mg/30 μg) in a 21/7-day regimen had at least 1 evaluable cycle for vaginal
bleeding analyses. The frequency of absent scheduled bleeding was higher (p<.0001)
for women using NOMAC/E2 than DRSP/EE across all 11 cycles (cycles 2–12), ranging
between 17.6% and 31.6% and between 3.4% and 5.8%, respectively. For women who had
absent scheduled bleeding in cycles 2, 3, or 4 the incidence of absent scheduled bleeding
in subsequent cycles was high and ranged between approximately 50%–60% for NOMAC/E2
and approximately 40%–50% for DRSP/EE. Amenorrhea increased over time with both regimens,
being higher with NOMAC/E2. Both absent scheduled bleeding and amenorrhea with NOMAC/E2
were more common in older women, overweight women, switchers, and smokers; unscheduled
bleeding was more common in starters, but had no association with age, body mass index,
and smoking.
Conclusions
NOMAC/E2 is associated with a higher prevalence of absent scheduled bleeding compared
with DRSP/EE. Absent scheduled bleeding and amenorrhea were associated with age, body
weight, switching and smoking. Unscheduled bleeding was more common in starters.
Implications
Information about the factors associated with bleeding patterns may help clinicians
provide guidance to women considering use of the NOMAC/E2 oral contraceptive.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to ContraceptionAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17 beta-oestradiol on ovarian function in comparison to a monophasic combined oral contraceptive containing drospirenone and ethinylestradiol.Eur J Contracept Reprod Health Care. 2010; 15: 314-325
- Nomegestrol acetate: pharmacology, safety profile and therapeutic efficacy.Drugs. 2010; 70: 541-559
- An overview of nomegestrol acetate selective receptor binding and lack of estrogenic action on hormone-dependent cancer cells.J Steroid Biochem Mol Biol. 2003; 87: 111-122
- Nomegestrol acetate: steroid receptor transactivation profile in Chinese hamster ovary cells and ovulation inhibition in rat and monkey.Contraception. 2011; 84: 199-204
- Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17β-oestradiol compared with one containing levonorgestrel and ethinylestradiol on haemostasis, lipids and carbohydrate metabolism.Eur J Contracept Reprod Health Care. 2011; 16: 444-457
- Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17β-oestradiol in comparison to one containing levonorgestrel and ethinylestradiol on markers of endocrine function.Eur J Contracept Reprod Health Care. 2011; 16: 458-467
- Inhibition of ovulation by NOMAC/E2, a novel monophasic oral contraceptive combining nomegestrol acetate and 17β-oestradiol: a double-blind, randomised, dose-finding pilot study.Eur J Contracept Reprod Health Care. 2011; 16: 76-84
- Comparison of a 24-day and a 21-day pill regimen for the novel combined oral contraceptive, nomegestrol acetate and 17β-estradiol (NOMAC/E2): a double-blind, randomized study.Hum Reprod. 2011; 26: 1338-1347
- Haemostatic effects of a new combined oral contraceptive, nomegestrol acetate/17β-estradiol, compared with those of levonorgestrel/ethinyl estradiol. A double-blind, randomised study.Thromb Haemost. 2011; 105: 560-567
- Efficacy and tolerability of a monophasic combined oral contraceptive containing nomegestrol acetate and 17β-oestradiol in a 24/4 regimen, in comparison to an oral contraceptive containing ethinylestradiol and drospirenone in a 21/7 regimen.Eur J Contracept Reprod Health Care. 2011; 16: 430-443
- Effects on bone mineral density of a monophasic combined oral contraceptive containing nomegestrol acetate/17β-estradiol in comparison to levonorgestrel/ethinylestradiol.Acta Obstet Gynecol Scand. 2012; 91: 1279-1285
- Efficacy, safety, and tolerability of a monophasic oral contraceptive containing nomegestrol acetate and 17β-estradiol: a randomized controlled trial.Obstet Gynecol. 2012; 119: 989-999
- Efficacy and safety of a new 24-day oral contraceptive regimen of norethindrone acetate 1 mg/ethinyl estradiol 20 micro g (Loestrin 24 Fe).Contraception. 2007; 75: 16-22
- Menstrual bleeding expectations and short-term contraception discontinuation in Mexico.Stud Fam Plann. 1983; 14: 127-133
- Pharmacokinetic profile of nomegestrol acetate and 17β-estradiol after multiple and single dosing in healthy women.Contraception. 2013; 87: 193-200
- Changing convention in combination oral contraceptives: estradiol and nomegestrol acetate in a monophasic 24/4 regimen.J Fam Plann Reprod Health Care. 2013; 39: 211-216
- Cycle control and bleeding pattern of a 24/4 regimen of drospirenone 3 mg/ethinylestradiol 20 μg compared with a 21/7 regimen of desogestrel 150 μg/ethinylestradiol 20 μg: a pooled analysis.Clin Drug Investig. 2011; 31: 519-525
- Cycle control with a 21-day compared with a 24-day oral contraceptive pill: a randomized controlled trial.Obstet Gynecol. 2009; 114: 1205-1212
- Women's and providers' attitudes toward menstrual suppression with extended use of oral contraceptives.Contraception. 2004; 70: 359-363
- Amenorrhea associated with contraception-an international study on acceptability.Contraception. 2003; 67: 1-8
- Preferred frequency and characteristics of menstrual bleeding in relation to reproductive status, oral contraceptive use, and hormone replacement therapy use.Contraception. 1999; 59: 357-362
Article info
Publication history
Published online: December 21, 2016
Accepted:
December 12,
2016
Received in revised form:
December 8,
2016
Received:
April 25,
2016
Footnotes
☆Role of the Funding Source: Financial support for the conduct of the research and the preparation of this article was provided by Merck & Co., Inc., Kenilworth, NJ, USA. The sponsor was involved in study design; in the collection, analysis and interpretation of data from the original studies; and in providing data for the present analysis.
☆☆Clinical trial registration numbers: NCT00413062 and NCT00511199.
★Conflicts of Interest: Dr. Mansour has received financial support to attend pharmaceutical advisory board meetings, undertake research studies, and to speak at educational meetings and conferences from Astellas, Bayer, Consilient Healthcare, HRA Pharma, Merck & Co., Inc., Pfizer, and Vifor Pharma. Dr. Korver is a former employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, and currently provides consultancy services to the company. Dr. Kher is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ. Dr. Westhoff is a DSMB member for FDA- and EMA-mandated post-approval safety studies sponsored by Bayer and Merck, including post-approval safety studies of both NOMAC/E2 and drospirenone oral contraceptives.
Identification
Copyright
© 2016 Elsevier Inc. All rights reserved.
