From the Editor

Big step forward and downward: An OC with 10 μg of estrogen

Lo Loestrin Fe delivers an ultra-low dose of ethinyl estradiol—a novel and noteworthy option when you’re considering an estrogen-progestin contraceptive.



Correction: Drug dosage, Editorial, April 2011

The subcutaneous dosage of terbutaline given in the “Checklist” on page 8 is incorrect. The dosage of terbutaline should be given as 0.25 mg.

We regret this editing error. The corrected “Checklist” appears at CLICK HERE

—The Editors

Let’s be honest, OK? The original estrogen-progestin oral contraceptives (OCs) contained far too much estrogen. True, they were effective—yielding a reliable pattern of uterine withdrawal bleeding—but those high, high-dose estrogen formulations, such as Enovid, also carried an excessive rate of deep venous thrombosis (DVT) and pulmonary embolism (PE). In the 1960s, many women turned away from OCs because they had a justifiable fear of side effects.

We’ve come a long way from the 1960s, when OCs that delivered a daily dose of 150 μg of mestranol (mestranol is 3-methoxy ethinyl estradiol) or 50 μg of ethinyl estradiol were widely prescribed. Now, effective low-dose OCs routinely deliver a daily dose of 20 to 30 μg of ethinyl estradiol. With that decrease in the dosage of estrogen, we have clearly observed a decrease in serious side effects, such as DVT and PE.

Now, Lo Loestrin FE (Warner Chilcott), which delivers a daily dose of 10 μg of ethinyl estradiol, represents the next big step in the historic march to an ever-lower dose of estrogen (see “The ultra-low estrogen formulation,” on this page). This is truly an extraordinary advance.

The ultra-low estrogen formulation

Lo Loestrin Fe comprises 28 tablets in this order:

  • 24 blue tablets, each containing 10 mg of ethinyl estradiol and 1 mg of norethindrone acetate
  • 2 white tablets, each containing 10 mg of ethinyl estradiol but no norethindrone acetate
  • 2 brown tablets, each containing 75 mg of ferrous fumarate only

How does the estrogen-progestin contraceptive work?

The principal mechanism of estrogen-progestin OCs is suppression of ovulation. They also work by altering endometrial development and reducing sperm transport from the vagina into the upper reproductive tract.

Estrogen-progestin pills that contain 30 to 35 μg of ethinyl estradiol have an ovulation suppression rate of 98%; those that contain 15 to 20 μg of ethinyl estradiol have an ovulation suppression rate of 99%. In contrast, progestin-only OCs (i.e., no estrogen) have an ovulation suppression rate of only 67%.1

Estrogen-progestin OCs likely work to suppress ovulation by decreasing hypothalamic kisspeptin activity. That decrease reduces gonadotropin-releasing hormone (GnRH) secretion, in turn 1) decreasing pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and 2) blocking development of a dominant ovarian follicle. In addition, estrogen-progestin contraceptives directly block LH and FSH release at the level of the pituitary.

In the absence of a dominant ovarian follicle, no LH surge occurs, and ovulation cannot occur.

The impact of 26 days of hormone-active pills

The standard estrogen-progestin OC has 21 active (containing hormone) tablets and 7 tablet days without hormonal treatment. The 7-day hormone-free interval is associated with increased LH and FSH secretion and increased ovarian follicle activity.

Adding estrogen-progestin pills or estrogen-only pills to the standard 7-day hormone-free interval (as Lo Loestrin Fe does) decreases both secretion of LH and FSH and ovarian follicle activity.2,3 By adding hormone treatment to the standard 7-day hormone-free interval, therefore, the daily dose of hormones can be decreased without reducing contraceptive efficacy. Lo Loestrin Fe takes advantage of this phenomenon by having 26 days of hormone treatment in every 28-day cycle. Instead of only 21 estrogen-progestin pills, Lo Loestrin Fe contains 24 estrogen-progestin pills and two estrogen-only pills.

20 μg or less of ethinyl estradiol: Benefits and side effects

In a clinical trial, women taking a higher dose (35 μg) of ethinyl estradiol (in a tricyclic preparation) were approximately 50% more likely to report bloating, breast tenderness, and nausea, compared with women taking a lower dose (20 μg) (in a monophasic formulation).4 It’s conceivable that an ultra-low estrogen pill will be associated with even fewer episodes of bloating, breast tenderness, and nausea than an OC containing a higher dose.

On the other hand, an ultra-low estrogen pill may be associated more often than a high-estrogen pill with abnormal patterns of bleeding. In a systematic review, contraceptives that contained 20 μg or less of ethinyl estradiol were associated with an increased risk of bleeding irregularities—including infrequent bleeding, prolonged or frequent bleeding, and unscheduled bleeding or spotting—than contraceptives that contained more than 20 μg of ethinyl estradiol.5

How potent a progestin is norethindrone acetate?

A widely used method of assessing the potency of a synthetic progestin in women is the so-called delay of menses test, based on the principle that surgical removal of a corpus luteum any time after ovulation results in uterine bleeding within 48 hours because of the withdrawal of progesterone support.


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