Desogestrel
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Desogestrel: From Contraception to Amenorrhea
One-Sentence Summary
Desogestrel is a progestin used in hormonal contraceptives and is currently marketed in Canada under 12 licences. The TxGNN model predicts it may be useful for amenorrhea, with 1 clinical trial (indirect relevance) and 11 publications currently supporting this direction. The evidence is limited and mostly indirect, because the trial does not clearly test desogestrel.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available from the Canadian licence data compiled for this report (desogestrel is a progestin used in oral contraceptives) |
| Predicted New Indication | Amenorrhea |
| TxGNN Prediction Score | 0.9996 |
| Evidence Level | L5 |
| Canada Market Status | Marketed (marketed DINs: 12 of 12) |
| Number of DINs | 12 (marketed: 12) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, desogestrel is a progestin that suppresses gonadotropins. It is used with ethinylestradiol in combined oral contraceptives, and its contraceptive use is well established. Mechanistically, it may be applicable to amenorrhea.
In hypothalamic oligo/amenorrhea, combined oral contraceptives are used to restore the hormonal environment and protect bone. One cohort study of young women with hypothalamic oligoamenorrhea treated with oral contraceptives examined bone mineral density.
There is an important limitation. The combined pill induces withdrawal bleeding rather than restoring natural ovulatory function. It therefore manages the condition and does not treat its cause. The bone-protection benefit of oral contraceptives in this setting also comes from the oestrogen component and is not specific to desogestrel.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00946192 | Phase 3 | Completed | 121 | Young athletes who stop menstruating compared with those who continue and with non-athletes. Tests whether transdermal or oral estrogen improves bone density in oestrogen-deficient adolescent athletes. Desogestrel is not confirmed as the intervention. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 11725730 | 2001 | Cohort | J Reprod Med | Bone mineral density in young women with hypothalamic oligoamenorrhea treated with oral contraceptives of decreasing ethinyl estradiol dose |
| 35261299 | 2022 | Cohort | Gynecol Endocrinol | Bleeding profile of a drospirenone-only pill versus desogestrel 0.075 mg; desogestrel shows poor cycle control |
| 8218004 | 1993 | Comparative clinical study | Br J Obstet Gynaecol | Two desogestrel pills (20 vs 30 µg ethinyl estradiol) compared for reliability, cycle control and side effects |
| 8447356 | 1993 | Tolerability study | Am J Obstet Gynecol | Tolerability of desogestrel/ethinyl estradiol; non-contraceptive benefits include reduced dysmenorrhea and endometriosis |
| 3161265 | 1985 | Pharmacodynamic study | Acta Obstet Gynecol Scand Suppl | Androgenicity of desogestrel, relevant to conditions such as PCOS with amenorrhea |
| 8324604 | 1993 | Review | Br Med Bull | Acceptability and effective use of combined oral contraceptives |
| 1436906 | 1992 | Review | Obstet Gynecol Surv | Pills containing the newer progestins gestodene, norgestimate and desogestrel |
| 2576257 | 1989 | Review | Int J Fertil | Overview of a gestodene triphasic contraceptive, with a desogestrel comparator study |
| 1604074 | 1992 | Review | Rev Med Liege | Overview of hormonal contraception |
| 7838435 | 1994 | Review | Nurse Pract | Brief review of combined oral contraceptive pills |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02410257 | MIRVALA 28 | Not listed | Not listed |
| 02272903 | LINESSA 21 | Not listed | Not listed |
| 02257238 | LINESSA 28 | Not listed | Not listed |
| 02556561 | MILEY 28 | Not listed | Not listed |
| 02556553 | MILEY 21 | Not listed | Not listed |
The other seven licences are APRI 28, APRI 21, MARVELON 28, MARVELON 21, MIRVALA 21, FREYA 28 and FREYA 21. All 12 licences are valid.
Safety Considerations
- Contraindication signals from the knowledge graph (these are model-derived drug-disease links, not label text): hypertension, epilepsy, anxiety and neurotic disorders, porphyria, liver disease, gallbladder disease, hyperglycaemia and diabetes mellitus, diabetic ketoacidosis, hypertriglyceridaemia, hypothyroidism, systemic lupus erythematosus, asthma, hypercalcaemia, female breast carcinoma, thrombophlebitis and uterine leiomyoma.
- Drug interactions: 43 interactions were identified, and the 20 listed are all rated Moderate. Most involve glucose-lowering agents, including insulins (aspart, degludec, detemir, glulisine, lispro, human), metformin, the DPP-4 inhibitors alogliptin and linagliptin, the GLP-1 agonists albiglutide, liraglutide and lixisenatide, the SGLT2 inhibitors dapagliflozin and ertugliflozin, nateglinide, rosiglitazone and metreleptin. Other interactions include aprepitant and glycerol phenylbutyrate.
- Literature in the data set also notes that combined oral contraceptives are associated with venous thromboembolism risk.
Please refer to the package insert for the official warnings and contraindications, which were not available for this report.
Conclusion and Next Steps
Decision: Hold
Rationale: The amenorrhea prediction has a high model score and a plausible role for hormonal therapy. However, the only clinical trial does not clearly test desogestrel and focuses on estrogen for bone health in athletes. The literature is mostly older reviews and small cohort studies. The combined pill induces bleeding and does not treat the cause of amenorrhea. The safety profile shows many contraindication signals, and label-based safety data have not yet been reviewed.
To proceed, the following is needed:
- Health Canada package insert warnings and contraindications, to allow safety screening
- Mechanism of action data from DrugBank
- Approved indication text for the Canadian licences, to confirm the original indication
- Desogestrel-specific clinical evidence in amenorrhea (for example hypothalamic or athlete-associated), separate from class effects of combined oral contraceptives
- Review of the cardiovascular and metabolic risks, particularly in patients with diabetes or hypertension
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.