Desogestrel

證據等級: L5

預測適應症: 10 個

Desogestrel: From Contraception to Amenorrhea

One-Sentence Summary

Desogestrel is a third-generation progestin used as a progestin-only contraceptive pill (75 mcg/day), indicated for pregnancy prevention in women of reproductive age. The TxGNN model predicts it may be effective for Amenorrhea, with 2 clinical trials and 16 publications currently supporting this direction — though the mechanistic relationship is complex and paradoxical, warranting caution before advancing to clinical development.

Quick Overview

Item	Content
Original Indication	Contraception (progestin-only oral contraceptive)
Predicted New Indication	Amenorrhea
TxGNN Prediction Score	99.96%
Evidence Level	L3
India Market Status	✗ Not Marketed
Number of Registrations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available for Desogestrel in this evidence pack. Based on known pharmacological information, Desogestrel is a third-generation progestin belonging to the gonane family and is classified as a prohormone — it must first be metabolised into its biologically active form (etonogestrel) in the liver. As a progestin-only pill (POP, Cerazette 75 mcg/day), it suppresses the LH surge and inhibits ovulation in approximately 97% of cycles, more consistently than first- and second-generation POPs. Through HPO (hypothalamic-pituitary-ovarian) axis modulation, it alters follicular development, cervical mucus viscosity, and endometrial receptivity without the estrogen component present in combined oral contraceptives.

The mechanistic relationship with amenorrhea is notably bidirectional and paradoxical for repurposing purposes. Clinically, 20–30% of Desogestrel POP users develop amenorrhea as a recognised side effect — meaning the drug is well-documented to suppress, not restore, menstruation. The TxGNN model likely identified the HPO axis interaction node shared between Desogestrel’s pharmacology and amenorrhea pathophysiology as a knowledge graph connection. However, using Desogestrel to treat amenorrhea (e.g., hypothalamic amenorrhea caused by energy deficiency, or primary amenorrhea from ovarian insufficiency) lacks mechanistic justification: these conditions already involve insufficient gonadotropin drive or ovarian reserve, which progestin monotherapy does not address and may exacerbate.

Both identified clinical trials confirm this concern — amenorrhea appears as an observed outcome or safety measure, not as a treatment target. The prediction therefore captures a real biological relationship, but in the wrong direction for a therapeutic claim. A narrower sub-indication (e.g., progestin-challenge test for anovulatory oligoamenorrhea, or cyclical withdrawal bleeding in PCOS-associated amenorrhea) might offer a more defensible pathway, but would require substantial evidence development.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00946192	Phase 3	Completed	121	Investigates fat-mediated modulation of reproductive/endocrine function in young athletes with exercise-induced amenorrhea; compares transdermal vs oral estrogen for bone density restoration. Desogestrel is not the primary intervention — amenorrhea is the patient population criterion, not the treatment target.
NCT01588873	Phase 4	Unknown	42	Compares hormonal contraceptive pill vs vaginal ring on androgen secretion, insulin/glucose metabolism, lipid profile, and SHBG in women with PCOS over 59 weeks. Amenorrhea is an observational outcome, not a therapeutic endpoint. Small sample and unknown completion status limit data reliability.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
18843653	2008	Systematic Review / Meta-analysis	Cochrane Database of Systematic Reviews	Compares 20 µg vs >20 µg estrogen COCs; lower estrogen doses associated with higher rates of amenorrhea and unscheduled bleeding — relevant background on dose-response relationship
21249657	2011	Systematic Review	Cochrane Database of Systematic Reviews	Updated Cochrane review confirming lower-dose estrogen formulations (including Desogestrel-containing pills) produce more irregular bleeding and amenorrhea
35261299	2022	Observational Study	Gynecological Endocrinology	Head-to-head comparison of Drospirenone 4 mg vs Desogestrel 75 mcg on bleeding patterns in women with cardiovascular risk factors; Desogestrel showed poor cycle control with amenorrhea in a significant proportion of users
3161265	1985	Pharmacodynamic Study	Acta Obstetricia et Gynecologica Scandinavica	Seminal pharmacodynamic evaluation of Desogestrel’s androgenicity compared to other progestogens; low androgenic profile documented; discusses PCO-related amenorrhea as comparative context
11725730	2001	Clinical Study	Journal of Reproductive Medicine	Evaluates different EE doses on bone mineral density in hypothalamic oligoamenorrhea; provides clinical context for OCP management of amenorrhea subtypes
8218004	1993	Comparative Trial	British Journal of Obstetrics and Gynaecology	RCT comparing Desogestrel 150 µg with 20 µg vs 30 µg EE (Mercilon vs Marvelon); higher amenorrhea and spotting rates with lower estrogen formulation
1436906	1992	Review	Obstetrical & Gynecological Survey	Overview of three new progestogens (Desogestrel, norgestimate, gestodene); Desogestrel described as a prohormone metabolised to etonogestrel, with lower androgenic activity than earlier-generation agents
8447356	1993	Review	American Journal of Obstetrics and Gynecology	Comprehensive tolerability profile of Desogestrel/EE combination; documents non-contraceptive benefits (dysmenorrhea, endometriosis, PID reduction) and menstrual pattern changes including amenorrhea
8324604	1993	Review	British Medical Bulletin	Reviews COC safety and efficacy in 60 million+ users; discusses clinical management based on dose, potency, and biological activity — relevant safety background
23221134	2012	Clinical Study	Georgian Medical News	Examines central genesis of dysfunctional menstrual disorders including oligomenorrhea and amenorrhea in infertile women (n=159); compares pathogenesis-directed management vs standard hormone therapy — provides context for hypothalamic amenorrhea treatment approaches

India Market Information

Desogestrel is currently not marketed in India. No drug registrations were identified in the regulatory database (total licenses = 0). This means there is no existing regulatory approval, pricing precedent, or distribution infrastructure to leverage for a repurposing pathway in the Indian market.

Safety Considerations

Drug Interactions (43 total interactions documented; representative moderate-level interactions shown below):

A notable clustering of interactions involves antidiabetic agents, reflecting Desogestrel’s known effect on glucose tolerance and insulin sensitivity. All listed interactions are Moderate severity (source: DDInter).

Interacting Drug	Level	Class / Clinical Relevance
Metformin	Moderate	Biguanide; progestins may impair glucose tolerance — monitor glycemic control
Insulin aspart, Insulin detemir, Insulin degludec, Insulin glulisine, Insulin lispro (protamine), Insulin human (zinc)	Moderate	Multiple insulin formulations; Desogestrel may reduce insulin sensitivity — dose adjustment may be needed
Liraglutide, Albiglutide, Lixisenatide	Moderate	GLP-1 receptor agonists; pharmacodynamic interaction via metabolic/hormonal axis
Dapagliflozin, Ertugliflozin	Moderate	SGLT2 inhibitors; monitor for changes in glycemic control during co-administration
Alogliptin, Linagliptin	Moderate	DPP-4 inhibitors; antidiabetic efficacy may be altered
Nateglinide	Moderate	Meglitinide; glucose-lowering effect may be diminished
Rosiglitazone	Moderate	Thiazolidinedione; monitor insulin sensitivity markers
Aprepitant	Moderate	NK1 receptor antagonist / CYP3A4 inducer; may reduce Desogestrel plasma concentrations, potentially reducing contraceptive efficacy
Glycerol phenylbutyrate	Moderate	Nitrogen scavenger; hormonal interaction pathway
Metreleptin	Moderate	Leptin analogue; potential interaction at the metabolic-reproductive hormonal axis

Please refer to the package insert for complete warnings and contraindications (TFDA prescribing information currently unavailable in this evidence pack).

Conclusion and Next Steps

Decision: Hold

Rationale: The TxGNN prediction connecting Desogestrel to amenorrhea reflects a pharmacologically real but therapeutically inverted relationship — clinical data consistently shows Desogestrel induces amenorrhea in 20–30% of users as an adverse effect, and neither of the identified clinical trials tests it as a therapy for amenorrhea. Combined with zero India market registrations and absent regulatory documentation, there is no viable near-term repurposing pathway for this indication as currently framed.

To proceed, the following is needed:

Indication refinement: Clarify whether a specific subtype of amenorrhea is hypothesised to benefit (e.g., progestin challenge-responsive anovulatory amenorrhea in PCOS, or cyclical withdrawal bleeding protocols) rather than amenorrhea as a broad category
MOA documentation: Retrieve full mechanism of action data from DrugBank (DB00304) to support or refute any therapeutic — rather than side-effect — rationale for the amenorrhea linkage
Regulatory data gap resolution: Download and parse the TFDA/CDSCO package insert PDF to obtain warnings, contraindications, and approved indication text (identified as a blocking data gap: DG001)
Targeted literature review: Conduct a focused search on progestin-only pills in the treatment of specific amenorrhea subtypes (hypothalamic, PCOS-associated, post-pill) to distinguish from the existing evidence base documenting amenorrhea as a POP side effect
Mechanistic plausibility workshop: If a specific subtype rationale is identified, a scientific advisory panel review is recommended before committing to any prospective study design
India regulatory pathway assessment: Given zero current registrations, a market entry strategy would need to be developed in parallel with any clinical development plan
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.