Progestins are classified according to their structure in C19 and C21 progestagens. The C19 ones are derived from testosterone, the C21 ones from progesterone. C21 progestagens include cyproterone acetate, dydrogesterone, medroxyprogesterone acetate, chlormadinone acetate, megestrol and promegestone. Of these, dydrogesterone is structurally most similar to progesterone. C19 progestagens include norethisterone, (levo)norgestrel, lynestrenol, desogestrel, norgestimate, gestodene and tibolone.

Different progestins have different combinations of androgen (testosterone-like) and progesterone activity. If the activity of 1 mg of norethindrone is taken as the baseline, 1 mg of the other progestins have activities as follows:

Norethindrone was synthetized for the first time in 1951 by the Mexican chemist Luis E. Miramontes. This substance became the basis for the contraceptive pill.

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OCs called 'fabulous' adjunctive Tx for acne
From OB/GYN News, 5/1/05 by Patrice Wendling

NEW ORLEANS -- Oral contraceptives are a safe and effective treatment for acne but are best used as adjunct therapy, Julie C. Harper, M.D., reported at the annual meeting of the American Academy of Dermatology.

Topical retinoids such as adapalene, tazarotene, and tretinoin remain the first-line treatment for all grades of acne, followed by oral or topical antibiotics, and then hormonal therapy.

"They [oral contraceptives] are fabulous to add to your acne treatment, but they aren't stand-alone medications or first-line treatments," Dr. Harper said.

Ortho Tri-Cyclen (norgestimate/ethinyl estradiol) and Estrostep (norethindrone acetate/ethinyl estradiol) have been approved by the Food and Drug Administration for the treatment of acne.

Newer contraceptives such as Yasmin, which contains the novel progestin drospirenone also are effective, said Dr. Harper of the department of dermatology at the University of Alabama, Birmingham.

A recent study showed that Yasmin was superior to Ortho Tri-Cyclen in reducing the total number of skin lesions in women with mild to moderate acne vulgaris after 6 months, and was rated superior by investigators for its therapeutic effect (Cutis. 2004;74:123-30).

Yasmin "tops" the other OCs in treating acne, but the difference is not dramatic, Dr. Harper said. It may take several months to see an improvement in acne on Yasmin, and she recommends a minimum of 3 months of treatment.

Yasmin combines ethinyl estradiol and 3 mg of drospirenone, a spironolactone analogue that has antimineralocorticoid and antiandrogenic activity. Androgens stimulate sebaceous epithelial cell (sebocyte) differentiation and sebum production. Excess sebum is a key factor in the development of acne.

All combined oral contraceptives have the potential to improve acne because they increase sex hormone-binding globulin, thereby decreasing serum androgen. This is true even when a woman's serum levels are in the normal range.

Most women with acne have normal circulating levels of androgen hormones, she said, adding that scientists now suspect an end-organ hyperresponsiveness to androgens in patients with acne.

OCs are used most safely to treat acne in younger women who don't smoke, do not have a history of migraines, and are normotensive. Dr. Harper will not prescribe OCs to women who smoke, are aged 35 years or older, or on rifampin.

Spironolactone 50-100 mg is recommended for women who aren't candidates for OCs and have failed conservative treatments.

The relative risk of breast cancer is 1.24 times higher in current OC users, she said.

The relative risk of stroke is 2.5 times higher in current contraceptive users, although there has been no evidence that Yasmin significantly increases thrombolytic events, compared with other OCs, Dr. Harper said.

BY PATRICE WENDLING

Chicago Bureau

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