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Progestational hormones

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Miramontes notebook

Luis E. Miramontes signed laboratory notebook. October 15, 1951

A progestin is a synthetic progestogen that has some biological activity similar to progesterone and is most well known for the applications in hormonal contraception, but progestins (and progesterone) also have applications in the treatment of dysmenorrhea, endometriosis, functional uterine bleeding, and amenorrhea. They have also been used to treat habitual miscarriages due to progesterone's role in sustaining pregnancy, but this has not always been successful due to the fact that miscarriage is not always due to hormonal deficiency.

The recognition of progesterone's ability to suppress ovulation during pregnancy spawned a search for a similar hormone that could bypass the problems associated with administering progesterone (low bioavailability when administered orally and local irritation and pain when continually administered parentally) and, at the same time, serve the purpose of controlling ovulation. The many synthetic hormones that resulted are known as progestins. Some examples of progestins that have been used in hormonal contraceptives are norethynodrel (Enovid), norethindrone (many brand names, most notably Ortho-Novum and Ovcon) norgestimate (Ortho Tricyclen, Ortho-Cyclen), norgestrel, levonorgestrel (Alesse, Trivora-28), medroxyprogesterone (Provera, Depo-Provera) and desogestrel.

The first orally active progestin, norethindrone (norethisterone), was synthesized in 1951 by the Mexican chemist Luis E. Miramontes at Syntex under the supervision of Carl Djerassi and George Rosenkranz, and was used in some of the first oral contraceptives in the early 1960s. Norethynodrel, an isomer of norethindrone, first synthesized in 1952 by Frank Colton at Searle, was the progestin used in Enovid, the first approved oral contraceptive in 1960.

Methods of progestin-based contraception Edit

It was found that the most effective method of contraception was with a combination of estrogen and progestin. This can be done in a monophasic, biphasic, or in a triphasic manner. In the monophasic method, both an estrogen and a progestin are administered for 20 or 21 days and stopped for a 7 or 8 day period that includes the 5 day menstrual period. Sometimes, a 28 day regimen is used that includes 6 or 7 inert tablets. Newer biphasic and triphasic methods are now used to more closely simulate the normal menstrual cycle. Yet another method is to administer a small dose of progestin only (no estrogen) in order to decrease certain risks associated with administering estrogen, but a major side effect is irregular bleeding that is usually observed during the first 18 months of such therapy.

Different progestins have different combinations of androgen (testosterone-like) activity 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: [How to reference and link to summary or text]

Progestin Progestational activity Androgen activity
norethindrone 1 1
norethindrone acetate 1.2 1.6
desogestrel 9 3.4
drospirenone 1.5 0
ethynodiol diacetate 1.4 0.6
norelgestromin 1.3 1.9
norgestimate 1.3 1.9
levonorgestrel 5.3 8.3
dl-norgestrel 2.6 4.2
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