Desogestrel
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Desogestrel: From Hormonal Contraception to Amenorrhea
One-Sentence Summary
Desogestrel is a progestin used in hormonal contraception and is marketed in Singapore as a single-ingredient tablet (Mercilon). The TxGNN model predicts it may be effective for amenorrhea, with 1 clinical trial and 11 publications currently linked to this direction. The trial does not clearly test desogestrel directly, and most of the publications are reviews or indirect studies.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available (the Singapore license record contains no approved indication text; the drug is known as a hormonal contraceptive) |
| Predicted New Indication | Amenorrhea |
| TxGNN Prediction Score | 99.96% |
| Evidence Level | L2 (capped, because the Phase 3 trial's intervention arms do not clearly include desogestrel) |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known information, desogestrel is a progestin that suppresses gonadotropin secretion. In combination with ethinylestradiol it can provide hormone replacement and endometrial support in hypothalamic oligo/amenorrhea.
The link between contraception and amenorrhea is mainly endocrine. Both involve regulation of the reproductive hormone axis. A cohort study of young women with hypothalamic oligoamenorrhea treated with oral contraceptives (PMID 11725730) examined bone mineral density, which supports biological plausibility.
There are important limits. The Phase 3 trial (NCT00946192) studies fat-mediated modulation of reproductive function in young athletes. It tests transdermal or oral estrogen, and it does not appear to test desogestrel directly. Direct randomized evidence for desogestrel in amenorrhea has therefore not been established.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00946192 | Phase 3 | Completed | 121 | Hormonal and body-composition differences in athletes with and without menstrual loss. Tests whether transdermal or oral estrogen improves bone density in estrogen-deficient adolescent athletes. Desogestrel's role is unconfirmed. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 11725730 | 2001 | Cohort/Clinical study | J Reprod Med | Bone mineral density in young women with hypothalamic oligoamenorrhea treated with oral contraceptives, comparing decreasing ethinyl estradiol doses |
| 8218004 | 1993 | Comparative clinical study | Br J Obstet Gynaecol | Two desogestrel 150 µg pills (20 µg vs 30 µg ethinyl estradiol) compared for reliability, cycle control and side effects |
| 3161265 | 1985 | Pharmacodynamic study | Acta Obstet Gynecol Scand Suppl | Androgenicity of desogestrel alone and with ethinylestradiol; relevant to conditions such as PCOS with amenorrhea |
| 8447356 | 1993 | Review | Am J Obstet Gynecol | Tolerability and non-contraceptive benefits of desogestrel/ethinyl estradiol |
| 8324604 | 1993 | Review | Br Med Bull | Acceptability, safety and effective use of combined oral contraceptives |
| 1436906 | 1992 | Review | Obstet Gynecol Surv | Newer progestogens (gestodene, norgestimate, desogestrel); desogestrel is a prohormone needing metabolic activation |
| 35261299 | 2022 | Clinical study | Gynecol Endocrinol | Bleeding profile of a drospirenone-only pill versus desogestrel 0.075 mg (different drug as the main subject) |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN06136P | MERCILON TABLET (N V Organon) | Tablet (oral) | Not recorded in the license data |
Safety Considerations
- Contraindication signals from the knowledge graph (drug-disease contraindication links, not label text): hypertension, epilepsy, porphyria, liver disease, gallbladder disease, diabetes mellitus and hyperglycemia, hypertriglyceridemia, hypothyroidism, systemic lupus erythematosus, asthma, thrombophlebitis, female breast carcinoma, uterine leiomyoma, hypercalcemia, and anxiety and dysthymic disorders.
- Drug Interactions: 43 interactions were found, and 20 moderate-level interactions are listed in the data. They are concentrated among antidiabetic agents (insulins, metformin, DPP-4 inhibitors, GLP-1 agonists, SGLT2 inhibitors, nateglinide, rosiglitazone, metreleptin). Others include aprepitant and glycerol phenylbutyrate.
- A literature item (PMID 10652979) addresses venous thromboembolism risk with combined oral contraceptives.
Please also refer to the package insert for full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: Amenorrhea has a very high model score and plausible hormonal biology. However, the only Phase 3 trial does not clearly test desogestrel, and the supporting literature is mostly reviews and indirect studies. Evidence does not yet support moving forward.
To proceed, the following is needed:
- Confirmation of the intervention arms of NCT00946192 (whether desogestrel is used at all)
- Direct comparative studies of desogestrel-containing regimens in hypothalamic or other amenorrhea
- Package insert warnings and contraindications from the HSA, plus approved indication text for SIN06136P
- Mechanism of action data
- A safety review for women with the contraindication signals listed above, including cardiovascular, metabolic and thromboembolic risk
Other predicted indications (for reference): Acne has the next strongest support (evidence level L2). Supporting studies (PMIDs 8894800, 8689881) compare desogestrel-containing combined pills with cyproterone acetate or gestodene, but the registered trial (NCT01466673) focuses on a norgestimate pill, and the effect is shared across combined oral contraceptives. Lactation disease (L4) reflects contraceptive use during lactation rather than treatment of a disease. The remaining predictions (benign breast conditions, breast abscess, primary ovarian failure, fragile X carrier symptoms) rest on model prediction alone, and several have no plausible mechanism.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.