Desogestrel is a progestin medication which is used in birth control pills. It is also used in the treatment of menopausal symptoms in women. The medication is available and used alone or in combination with an estrogen. It is taken by mouth.
Side effects of desogestrel include menstrual irregularities, headaches, nausea, breast tenderness, mood changes, acne, increased hair growth, and others. Desogestrel 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 very weak androgenic and glucocorticoid activity and no other important hormonal activity. The medication is a prodrug of etonogestrel (3-ketodesogestrel) in the body.
Desogestrel was discovered in 1972 and was introduced for medical use in Europe in 1981. It became available in the United States in 1992. Desogestrel is sometimes referred to as a "third-generation" progestin. Like norethisterone and Norgestrel, Desogestrel is widely available as a progestogen-only "mini pill" for birth control. Desogestrel is marketed widely throughout the world. It is available as a generic medication. In 2020, the version with ethinylestradiol was the 120th most commonly prescribed medication in the United States, with more than 5million prescriptions.
Medical uses Desogestrel is a hormone blocker, progesterone receptors agonist, and antiandrogen. It is used in conjunction with estrogens and testosterones. Medications containing desogestrel and estrogen are used to treat endometriosis and as a component of menopausal hormone therapy. While commonly used as a female contraceptive, desogestrel suppresses spermogenesis and has been shown to have potential as a male contraceptive.
Desogestrel and norethisterone are the only progestins that are widely used as a progestogen-only "mini pill". It is also the only newer-generation progestin with reduced androgenic activity that is used in such formulations.
Available forms
Desogestrel is available alone in the form of 75 μg oral tablets and at a dose of 150 μg in combination with 20 or 30 μg ethinylestradiol in oral tablets. These formulations are all indicated specifically for contraceptive purposes.
Contraindications Contraindications of desogestrel include: Allergy to desogestrel or any other ingredients Active thrombosis (deep vein thrombosis or pulmonary embolism) Jaundice or severe liver disease Hormone-sensitive cancers (e.g., breast cancer) Unexplained vaginal bleeding
Desogestrel is not indicated for use in pregnancy. It is not contraindicated during lactation and breastfeeding.
Side effects
Common side effects of desogestrel may include menstrual irregularities, amenorrhea, headaches, nausea, breast tenderness, and mood changes (e.g., depression), as well as weight gain, acne, and hirsutism. However, it has also been reported to not adversely affect weight. In addition, acne and hirsutism are negligible when combined with ethinylestradiol, and this combination can actually be used to treat such symptoms. Desogestrel can also cause changes in total, , and cholesterol. Uncommon side effects of desogestrel may include vaginal infection, contact lens intolerance, vomiting, hair loss, dysmenorrhea, ovarian cysts, and fatigue, while rare side effects include rash, urticaria, and erythema nodosum. Breast discharge, ectopic pregnancies, and aggravation of angioedema may also occur with desogestrel. Serious side effects of combined oral contraceptives containing desogestrel may include venous thromboembolism, arterial thromboembolism, hormone-dependent tumors (e.g., liver tumors, breast cancer), and melasma.
Overdose No serious harmful effects have been reported with overdose of desogestrel. Symptoms may include nausea, vomiting, and, in young girls, slight vaginal bleeding. In safety studies, dosages of up to 750 μg/day desogestrel in women showed no adverse effects on laboratory and various other parameters and produced no reported subjective side effects. There is no antidote to desogestrel overdose and treatment should be based on symptoms.
Interactions
Inducers of liver enzymes can increase the metabolism of desogestrel and etonogestrel and reduce their circulating levels. This may result in contraceptive failure. Examples of liver enzyme inducers include barbiturates (e.g., phenobarbital), bosentan, carbamazepine, efavirenz, phenytoin, primidone, rifampicin, and possibly also felbamate, griseofulvin, oxcarbazepine, rifabutin, St. John's Wort, and topiramate. Many antivirals for HIV/AIDS and HCV, such as boceprevir, nelfinavir, nevirapine, ritonavir, and telaprevir, may increase or decrease levels of desogestrel and etonogestrel. CYP3A4 inhibitors including strong inhibitors like clarithromycin, itraconazole, and ketoconazole and moderate inhibitors like diltiazem, erythromycin, and fluconazole may increase levels of desogestrel and etonogestrel. Hormonal contraceptives may interfere with the metabolism of other drugs, resulting in increased levels (e.g., ciclosporine) or decreased levels (e.g., lamotrigine).
Pharmacology
Pharmacodynamics
Desogestrel is a prodrug of etonogestrel (3-ketodesogestrel), and, via this active metabolite, it has progestogenic activity, antigonadotropic effects, very weak androgenic activity, very weak glucocorticoid activity, and no other hormonal activity.
Relative affinities (%) of desogestrel and metabolites Compound Desogestrel 1 0 0 0 0 0 0 Etonogestrel () 150 20 0 14 0 15 0 3α-Hydroxydesogestrel 5 0 0 ? ? ? ? 3β-Hydroxydesogestrel 13 3 2 ? ? ? ? 5α-Dihydroetonogestrel 9 17 0 ? ? ? ? 3α-Hydroxy-5α-dihydroetonogestrel 0 0 0 ? ? ? ? 3β-Hydroxy-5α-dihydroetonogestrel 1 0 1 ? ? ? ? Notes: Values are percentages (%). Reference ligands (100%) were promegestone for the , metribolone for the , for the , for the , aldosterone for the , for , and cortisol for . Sources:
Progestogenic activity Desogestrel is a progestogen, or an agonist of the progesterone receptor (PR). It is an inactive prodrug of etonogestrel with essentially no affinity for the PR itself (about 1% of that of promegestone). Hence, etonogestrel is exclusively responsible for the effects of desogestrel. Etonogestrel has about 150% of the affinity of promegestone and 300% of the affinity of progesterone for the PR. Desogestrel (via etonogestrel) is a very potent progestogen and inhibits ovulation at very low doses, in the low microgram range. The effective minimum dosage for inhibition of ovulation is 60 μg/day desogestrel (alone, not in combination with an estrogen). However, some studies in combination with oral estradiol have suggested that higher doses may be necessary. Desogestrel and etonogestrel are among the most potent progestogens available, along with gestodene and levonorgestrel (which have effective ovulation-inhibiting dosages 40 μg/day and 60 μg/day, respectively). Oral desogestrel is clinically on the order of 5,000 times more potent than oral micronized progesterone (which has an effective ovulation-inhibiting dosage of more than 300 mg/day) in humans.
Due to its progestogenic activity, desogestrel has potent functional antiestrogenic effects in certain tissues. It dose-dependently antagonizes the effects of ethinylestradiol on the vaginal epithelium, cervical mucus, and endometrium, with marked progestogenic effects occurring at a dosage of 60 μg/day. There is a rise in body temperature in some women at 30 μg/day and in all women at 60 μg/day. Desogestrel also has antigonadotropic effects, which are similarly due to its progestogenic activity. The contraceptive effects of desogestrel in women are mediated not only by prevention of ovulation via its antigonadotropic effects but also by its marked progestogenic and antiestrogenic effects on cervical mucus and the endometrium.
Aside from its progestogenic activity, desogestrel also has some off-target hormonal activity at other steroid hormone receptors (see below). However, these activities are relatively weak, and desogestrel is said to be one of the most selective and pure progestogens used in oral contraceptives.
Antigonadotropic effects Desogestrel has antigonadotropic effects via its progestogenic activity, similarly to other progestogens. It has been found to reduce testosterone levels by 15% in women at a dosage of 125 μg/day. In addition, desogestrel has been extensively investigated as an antigonadotropin at dosages of 150 to 300 μg/day in combination with testosterone in male contraceptive regimens. One study found that 150 μg/day and 300 μg/day desogestrel alone in healthy young men suppressed luteinizing hormone (LH) levels by about 35% and 42%, respectively; follicle-stimulating hormone (FSH) levels by about 47% and 55%, respectively; and testosterone levels by about 59% and 68%, respectively. LH levels were suppressed maximally by desogestrel within 3 days, whereas 14 days were necessary for maximal suppression of FSH and testosterone levels. A previous study by the same authors found that increasing the dosage of desogestrel from 300 μg/day to 450 μg/day resulted in no further suppression of gonadotropin concentrations. The addition of a low dose of 50 or 100 mg/week intramuscular testosterone enanthate after 3 weeks increased testosterone levels and further suppressed LH and FSH levels, to the limits of assay detection (i.e., to undetectable or near-undetectable levels), in both the 150 μg/day and 300 μg/day desogestrel groups. Upon cessation of treatment, levels of LH, FSH, and testosterone all recovered to baseline values within 4 weeks.
Androgenic activity Etonogestrel has about 20% of the affinity of metribolone and 50% of the affinity of levonorgestrel for the androgen receptor (AR) while desogestrel has no affinity for this receptor. The 5α-reduced metabolite of etonogestrel, 5α-dihydroetonogestrel (3-keto-5α-dihydrodesogestrel), also has some affinity for the AR (about 17% of that of metribolone). Desogestrel (via etonogestrel) has very low androgenic potency, about 1.9 to 7.4% of that of methyltestosterone in animal assays, and hence is considered to be a very weak androgen. Although etonogestrel has about the same affinity for the AR as norethisterone, due to the relatively increased progestogenic potency and decreased androgenic activity of etonogestrel, the drug has markedly higher selectivity for the PR over the AR than older 19-nortestosterone progestins like norethisterone and levonorgestrel. Conversely, its selectivity for the PR over the AR is similar to other newer 19-nortestosterone progestins like gestodene and norgestimate. It has been estimated that 150 μg/day desogestrel has less than one-sixth of the androgenic effect of 1 mg/day norethisterone (these being common dosages of the drugs used in combined oral contraceptives). Clinical studies with norethisterone even at very high dosages (e.g., 10 to 60 mg/day) have observed only mild androgenic effects in a minority of women including acne, increased sebum production, hirsutism, and slight virilization of female fetuses.