ORAL CONTRACEPTIVES STUDIED IN ACNE

Many oral contraceptives have been studied in the treatment of acne (Table 3).
These include those containing ethinyl estradiol in combination with cyproter-
one acetate (Diane, Dianette), ethynodiol diacetate (Demulen), levonorgestrel
(TriPhasil, Alesse), norgestimate (Ortho Tri-Cyclenw), desogesterel (Desogen),
and drosperinone (Yasmin, Yaz). Numerous studies point to the efficacy of
ethinyl estradiol/cyproterone acetate oral contraceptives (Diane and Dianette) in
the treatment of acne. Reductions in inflammatory lesion count on the order of
50% to 75% have been reported (44,45). Two large studies involving a total of
approximately 500 women with moderate acne were conducted with ethinyl
estradiol 35 mg/norgestimate (Ortho Tri-Cyclen). Improvement in inflammatory
lesions, total lesions, and global assessment was noted with this oral contraceptive
after six months of treatment (46,47). There was a 50% to 60% improvement in
inflammatory lesions. Decreases in serum free testosterone and an increase in sex
hormone-binding globulin were noted in the active group. Two large, six-month,
placebo-controlled trials (350 and 371 women, respectively) were conducted
using ethinyl estradiol 20 mg/levonorgestrel (Alesse) in the treatment of acne
(48,49). In each study, the oral contraceptive demonstrated significantly greater
reduction in acne lesion counts and improvement in global assessment scores com-
paredwith placebo. The reduction in inflammatory lesion count was on the order of
47%. A study of 128 women with mild-to-moderate acne compared the efficacy of
ethinyl estradiol 30 mg/drospirenone (Yasmin) and ethinyl estradiol 35 mg/cypro-
terone acetate (Diane-35) in the treatment of acne for nine cycles (50). Both treat-
ments produced comparable reductions in acne lesion counts, with an
approximate 60% reduction in inflammatory lesion count. Both treatments also
reduced sebum production and yielded comparable increases in sex hormone-
binding globulin. Two large placebo-controlled studies involving a total of approxi-
mately 593 women with moderate acne, found improvement in inflammatory
lesions, total lesions, global assessment, and quality of life in women who were
treated for six months with a triphasic oral contraceptive that contains doses of
20 to 35 mg of ethinyl estradiol in combination with 1.0 mg norethindrone acetate
(Estrostep) (51). In these studies, inflammatory lesion counts were reduced by
approximately 47% (51).
Oral contraceptives that have been approved for the treatment of acne in the
United States include ethinyl estradiol 35 mg/norgestimate (Ortho Tri-Cyclen)
ethinyl estradiol 20 to 35 mg/norethindrone acetate (Estrostep), and ethinyl estra-
diol 20 mg/drospirenone (Yaz).
ORAL CONTRACEPTIVES AND ANTIBIOTICS
The concern regarding oral contraceptives and antibiotics is essentially theoretical,
owing to the action of broad-spectrum antibiotics, which reduce the gut flora bac-
teria and thus may result in decreased absorption of estrogen. This could lead to a
possible reduction in the efficacy of oral contraceptives, although pharmacokinetic
studies suggest that serum levels of estrogen are unaffected by antibiotics such as
tetracycline, doxycycline, and others (52,53). Nevertheless, there have been very
few reports in the literature of pregnancies associated with the use of antibiotics
in conjunction with oral contraceptives (54,55). Existing reports have focused on
tetracycline, and the incidence was 1.2 to 1.4 pregnancies/100 woman years of
use of the oral contraceptive. These data are no greater than the background
failure rate of oral contraceptives (54,55).
NEWER FORMS OF CONTRACEPTIVES
Recently, newer forms of contraceptives have been developed, such as contracep-
tive patches, vaginal rings, and injectable combination hormones. Each of these is
designed to suppress ovulation and in this regardwill lower the ovarian production
of androgens. As of yet, these formulations have not been studied in the treatment
of acne. The contraceptive patch (Ortho Evra) contains 20 mg of ethinyl estradiol
and 150 mg of the progestin, norelgestromin. The patch is worn for three weeks
and removed for one week, during which time menstrual bleeding will occur.
The advantages of this formulation are better patient compliance, dosing that is
not affected by gastrointestinal disturbances, and more consistent serum levels of
estrogen serum levels compared to oral dosing (56). The vaginal ring (NuvaRing)
is a contraceptive vaginal ring that releases 15 mg of ethinyl estradiol and 120 mg
of the progestin, etonogestrel. It is placed within the vagina for three weeks and
removed for one week. In one study, the incidence of irregular bleeding was less
compared with an oral combination contraceptive (57). An injectable combination
of estradiol cypionate and medroxyprogesterone acetate (Lunelle) has been devel-
oped. This is given as a monthly contraceptive injection. Contraceptive efficacy was
shown to be comparable to a triphasic oral contraceptive containing ethinyl estra-
diol and norethindrone (Ortho 7/7/7) (58).