Oral contraceptives:  Does formulation matter?

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Applied Evidence

Oral contraceptives: Does formulation matter?

J Fam Pract. 2013 October;62(10):E1 - E12

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References

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28. Foidart JM, Wuttke W, Bouw GM, et al. A comparative investigation of contraceptive reliability, cycle control, and tolerance of two monophasic oral contraceptives containing either drospirenone or desogestrel. Eur J Contracept Reprod Health Care. 2000;5:124-134.

29. Hussain, SF. Progestogen-only pills and high blood pressure: is there an association? A literature review. Contraception. 2004;69:89-97.

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38. Wong CL, Farquhar C, Roberts H, et al. Oral contraceptive pill for primary dysmenorrhoea. Cochrane Database Syst Rev. 2009, Issue 4.

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40. Brill K, Then A, Beisiegel U, et al. Investigation of the influence of two low-dose monophasic oral contraceptives containing 20 micrograms ethinylestradiol/75 micrograms gestodene and 30 micrograms ethinylestradiol/75 micrograms gestodene, on lipid metabolism in an open randomized trial. Contraception. 1996;54:291-297.

41. Barkfeldt J, Virkkunen A, Dieben T. The effects of two progestogen-only pills containing either desogestrel (75 mcg/day) or levonorgestrel (30 mcg/day) on lipid metabolism. Contraception. 2001; 64:295-299.

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Another RCT examined the difference in bleeding patterns, side effects, and acceptability between a standard 28-day cycle OC and an extended regimen 168-day cycle OC in 32 women. Both OCs contained 20 mcg EE and 100 mcg LNG, and the study was conducted over 6 months. Women in the extended cycle regimen reported significantly fewer days of bloating (0.7 vs 11.1 days; P=0.04), and menstrual pain (1.9 vs 13.3 days; P<0.01). There was no significant difference in reported headache, breast tenderness, nausea, depression, or premenstrual symptoms. Women in the extended cycle group also reported significantly fewer bleeding days that required sanitary pads (18.4 vs 33.8 days; P<0.01). However, there was no statistically significant difference in the total number of days where any degree of bleeding occurred (34.9 days in the monthly cycle group, 25.9 days in the extended cycle group; P=0.33).²⁰

In a study of 126-day extended-cycle OCs with 30 mcg EE and 3 mg drospirenone, the bleeding profile improved over time and endometrial biopsies revealed no hyperplasia.²¹ Another benefit of the extended cycle is personal preference, ie, controlling the timing of one’s menses,²² for example, in athletes during training and competition.

Continuous use of OCs prevents the cyclic fluctuations of serum levels of EE and progestogen and, hence, the cyclic variations of related serum-based metabolic parameters. Extended cycle OCs can make it easier to titrate other medications affected by hormonal fluctuations. Another study of extended cycle drospirenone OCs compared with monthly OCs over 6 months showed no difference in lipid, carbohydrate, and coagulation markers.²³

Six RCTs were reviewed in a Cochrane review of monthly vs extended cycle combined pills. It found no significant differences in efficacy, adherence, discontinuation rates, and patient satisfaction. The only difference was improvement of menstrual-associated symptoms of “headaches, genital irritation, tiredness, bloating and menstrual pain” with the extended cycle regimen.²⁴

OCs effect on weight, BP, and premenstrual symptoms

Weight gain. A 2008 Cochrane review examined 3 placebo-controlled RCTs and concluded that the available evidence was insufficient to determine the effect of combined hormonal contraceptives on weight, and that larger doses of estrogen were not shown to cause larger weight gain.²⁵

One RCT examined the effects of OCs on variations of total body water, fat mass, and fat-free mass throughout the menstrual cycle to determine if different doses of estrogen (15 mcg vs 30 mcg EE) or different types of progestins (gestodene 60 mcg vs drospirenone 3 mg) impact weight gain. This study only included 80 women randomized to the 2 treatment groups and an additional control group using male condoms. No differences were found in total body water or fat mass. There was, however, a significant increase in the fat-free mass in women of the EE/gestodene group when compared to controls, indicating a possible effect of the androgenic properties of gestodene compared with drospirenone (which has anti-androgen properties) in increasing muscle mass.²⁶

In a 6 month study of drospirenone compared with LNG, mean body weight fell by 0.8 to 1.7 kg in women treated with drospirenone compared with a 0.7 kg weight gain in the LNG group (P < 0.05).²⁷ A multicenter RCT comparing OCs with EE 30 mcg/drospirenone 3 mg, and EE 30 mcg/desogestrel 150 mcg, concluded that EE/drospirenone has a more favorable effect on body weight than EE/desogestrel. This finding may have resulted from the antimineralocorticoid, mild diuretic effects of drospirenone.²⁸

Hypertension. In a review of progestin-only OCs in normotensive women, the authors could find no evidence to show a statistically significant increase in blood pressure.²⁹

In a study of 120 women randomized to drospirenone/EE or LNG/EE, the drospirenone group had a mean decrease in systolic blood pressure from 107 to 103 mm Hg, and a significantly lower group mean blood pressure compared with the LNG group.³⁰ Another study of 80 women over 6 months randomized into 3groups each having 3 mg of drospirenone with either a 30-, 20-, or 15-mcg dose of EE found that systolic blood pressure decreased by 1 to 4 mm Hg compared with an elevation of blood pressure of 4 mm Hg in the LNG/EE group.²⁷

In women with well-controlled blood pressure who were less than 35 years old, non-smokers and otherwise healthy, the American College of Obstetricians and Gynecologists (ACOG) recommends³¹ a trial of OCs with monitoring of their blood pressure.

Acne. One Cochrane review looked at studies that compared combined OCs to placebo, and found OCs improved the condition. However, there was insufficient evidence regarding the difference in effectiveness of various formulations of OCs in treating the disease.³² There was no difference between first and second generation progestins,³³ between second and third generations,³⁴ or third generation vs drospirenone.³⁵