Gestodene, sold under the brand names Femodene and Minulet among others, is a progestin medication which is used in birth control pills for women. It is also used in menopausal hormone therapy. The medication is available almost exclusively in combination with an estrogen. It is taken by mouth.
Side effects of the combination of an estrogen and gestodene include menstrual irregularities, headaches, nausea, breast tenderness, mood changes, and others. Gestodene is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone. It has weak androgenic activity, weak antimineralocorticoid activity, and weak glucocorticoid activity.
Gestodene was discovered in 1975 and was introduced for medical use, specifically in birth control pills, in 1987. It was subsequently introduced for use in menopausal hormone therapy as well. Gestodene is sometimes referred to as a "third-generation" progestin. It is marketed in birth control pills widely throughout the world, whereas it is available for use in menopausal hormone therapy only a few countries. Gestodene is not approved in the United States.
Medical uses
Gestodene is neutral in terms of androgenic activity, meaning that contraceptive pills containing gestodene do not exhibit the androgenic side effects (e.g., acne, hirsutism) sometimes associated with second-generation contraceptive pills such as those containing levonorgestrel.
The estrogen dosage in third-generation contraceptive pills (including those containing gestodene) is lower than that in second-generation oral contraceptives, reducing the likelihood of weight gain, breast tenderness, and migraine.
Third-generation oral contraceptives are also suitable for use in patients with diabetes or lipid disorders because they have minimal impact on blood glucose levels and the lipid profile.
Gestodene is also available in combination with estradiol for use in menopausal hormone therapy.
Available forms
Contraceptive products containing gestodene include:
Melodene-15, Mirelle, and Minesse which contain 15 μg of ethinylestradiol and 60 μg of gestodene; Meliane, Sunya, Femodette, and Millinette 20/75 which contain 20 μg of ethinylestradiol and 75 μg of gestodene; and Gynera, Minulet, Femoden, Femodene, Katya and Millinette 30/75 which contain 30 μg of ethinylestradiol and 75 μg of gestodene.
Contraindications
Side effects
Women who take oral contraceptives containing gestodene are 5.6 times as likely to develop venous thromboembolism than women who do not take any contraceptive pill, and 1.6 times as likely to develop venous thromboembolism compared to women taking oral contraceptives containing levonorgestrel.
Overdose
Contraindications
Pharmacology
Pharmacodynamics
Gestodene is a highly potent progestogen, and also possesses weak androgenic, antimineralocorticoid, and glucocorticoid activity. Due to its progestogenic activity, it has antigonadotropic and functional antiestrogenic effects. The medication has little or no estrogenic and no antiandrogenic activity.
Progestogenic activity
Gestodene is a progestogen, and hence is an agonist of the progesterone receptor. Based on the dosage necessary to inhibit ovulation in women, gestodene is the most potent of all of the currently used oral contraceptive progestogens. The oral dosage of gestodene required for ovulation inhibition is 30 or 40 μg per day. This is about 10,000 times lower than the oral dosage of progesterone required to inhibit ovulation (300 mg/day). A dosage of gestodene of 75 μg/day is used in contraceptives.
Androgenic activity
Gestodene has relatively high affinity for the androgen receptor (AR), with twice that of levonorgestrel (which is known to be one of the more androgenic 19-nortestosterone derivatives). However, the ratio of progestogenic to androgenic effects of gestodene is distinctly higher than that of levonorgestrel, and the increase in sex hormone-binding globulin (SHBG) levels (a marker of androgenicity) produced by oral contraceptives containing gestodene is slightly less than that produced by oral contraceptives containing desogestrel (which is known to be one of the more weakly androgenic 19-nortestosterone derivatives). In addition, no difference in acne incidence has been observed with oral contraceptives containing gestodene and oral contraceptives containing desogestrel. Gestodene may also act to some extent as a 5α-reductase inhibitor. Taken together, like desogestrel, gestodene appears to have a low potential for androgenic effects.