The potency of a specific dose of a progestin is tested by administering the compound daily, starting on Day 20 or Day 21 of the cycle, and continuing to do so for at least 21 days. To help improve the reliability of the test, 100 μg of mestranol is also given daily to stabilize estrogen levels during the testing interval. If menses do not occur until after the 21 days of progestin, that dose is considered adequate to support the endometrium.
Using this approach to assess the potency of progestin, norethindrone acetate is about twice as potent as an equivalent amount of norethindrone. 6,7
Lo Loestrin Fe contains 24 pills with 1 mg of norethindrone acetate; each pill, therefore, is pharmacologically equivalent to a pill that contains 2 mg of norethindrone. Because norethindrone, at a daily dose of 0.35 mg, is an FDA-approved progestin-only contraceptive, it isn’t surprising that a dose of norethindrone acetate equivalent to 2 mg of norethindrone, for 24 out of 28 days each cycle, would also be an effective contraceptive.
Circumstances in which a low-estrogen OC might be especially useful
Pelvic pain caused by endometriosis. Endometriosis is an estrogen-dependent disease process that responds well to interventions that reduce ovarian estrogen production, such as bilateral oophorectomy or hormone therapy with a GnRH analogue, progestin or danazol.8 Although the notion is somewhat counterintuitive, an estrogen-progestin OC is also effective for treating the pelvic pain caused by endometriosis.9,10
The progestin dominance of the modern estrogen-progestin pill probably accounts for why it is an effective treatment for endometriosis. Given that endometriosis is an estrogen-dependent disease process, it would be logical to use an estrogen-progestin OC with the lowest dose of estrogen, to avoid stimulating the growth of endometriosis lesions. The 10 μg of ethinyl estradiol in Lo Loestrin Fe makes it an interesting option for treatment of an estrogen-dependent disease.
After surgery for endometriosis, an estrogen-progestin OC may help prevent the return of pelvic pain, regrowth of endometriosis lesions, and recurrence of endometriosis ovarian cysts.11,12 An ultra-low-dose estrogen-containing contraceptive may therefore deserve consideration for long-term treatment following surgery for endometriosis.
The perimenopausal woman. During the perimenopause, many women have cycles characterized by markedly abnormal hormone levels. For example, some cycles in perimenopausal women are characterized by excessively high estradiol secretion and very low progesterone secretion. Other cycles are characterized by low estradiol secretion for an extended length of time. These abnormal patterns of hormone secretion contribute to menstrual cycle length irregularity, menorrhagia, and vasomotor symptoms.
Treatment with a progestin-dominant OC is often a first-line option for these women. Because Lo Loestrin Fe contains an ultra-low dose of ethinyl estradiol, it might be a good option for perimenopausal women who suffer a menstrual disorder.
The young smoker. Approximately 27% of women between the ages of 18 to 44 years who smoke use an OC; 35% of nonsmoking women in the same age range use an oral contraceptive.13 When I think about prescribing an OC to a smoker, I always vividly recall the black-box warning in the Food and Drug Administration’s prescribing information for all estrogen-progestin contraceptives:
Women over 35 years old who smoke should not use an estrogen-progestin contraceptive and cigarette smoking increases the risk of serious cardiovascular events from estrogen-progestin use.
I know that the progestin is likely not the cause of these associations, and that higher doses of estrogen are associated with an increased risk of cardiovascular events. Consequently, it seems prudent, when considering an estrogen-progestin OC for a young smoker, to prescribe the lowest dose of ethinyl estradiol available.
A basic principle of pharmacology applies
The lowest effective dose of a drug is, we know, typically a good choice because it’s likely to minimize the risk of side effects. The history of the oral contraceptive is characterized by a continuous decrease in the daily dose of ethinyl estradiol—and that downward trend has prevented many cases of DVT and PE. Lo Loestrin Fe, delivering an ultra-low dose—10 μg daily—of ethinyl estradiol, is a novel option for women in whom you are considering an estrogen-progestin contraceptive.
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