Medroxyprogesterone Acetate

證據等級: L5

預測適應症: 10 個

Medroxyprogesterone Acetate: From Original Indication (Not Documented) to Amenorrhea

One-Sentence Summary

The original approved indication for Medroxyprogesterone Acetate could not be determined from this Evidence Pack — the drug is not currently marketed in this jurisdiction and no license records or mechanism-of-action data are available. The TxGNN model predicts it may be effective for Amenorrhea, supported by 10 clinical trials and 20 publications, though only one trial (terminated) directly targets this indication. Because Medroxyprogesterone Acetate (as DMPA) is already well known clinically to induce amenorrhea as a hormonal effect, this is best understood as evidence consolidation of an established pharmacological effect rather than a novel repurposing hypothesis.

Quick Overview

Item	Content
Original Indication	Not documented in this Evidence Pack
Predicted New Indication	Amenorrhea
TxGNN Prediction Score	99.9994%
Evidence Level	L1
New Zealand Market Status	Not Marketed
Number of Authorizations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Currently, detailed mechanism-of-action data is not available from DrugBank in this Evidence Pack (flagged as a High-severity data gap). Based on the repurposing rationale supplied with the prediction, Medroxyprogesterone Acetate is a potent progestin that, with sustained use, induces endometrial atrophy and decidualization — a well-documented pharmacological effect that directly causes amenorrhea. This is precisely the mechanism behind the known side effect of Depot Medroxyprogesterone Acetate (DMPA) injectable contraception, and the compound is also used clinically as a "progestin challenge test" to evaluate the cause of amenorrhea.

Because the original approved indication is not recorded in this pack, the relationship between the (undocumented) original indication and amenorrhea cannot be formally assessed here. However, the mechanistic pathway itself is textbook-level, well-established pharmacology rather than a novel hypothesis — it reflects consolidation of existing clinical knowledge into a structured evidence base rather than discovery of an unexpected new effect.

Since this mechanistic link is already considered established clinical knowledge, the primary value of this prediction is in formalizing existing real-world evidence (e.g., DMPA-induced amenorrhea, progestin withdrawal bleeding physiology) rather than opening a new therapeutic hypothesis requiring exploratory trials.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT02449161	Phase 3	Terminated	60	Most directly relevant trial: effect of post-endometrial-ablation Medroxyprogesterone Acetate on amenorrhea rates; RCT terminated before completion
NCT01463202	Phase 4	Completed	184	Timing of postpartum DMPA administration and its effect on breastfeeding continuation, contraceptive continuation, and postpartum depression
NCT00808132	Phase 3	Completed	1886	Large double-blind RCT of bazedoxifene/conjugated estrogens on endometrial hyperplasia and osteoporosis prevention in postmenopausal women
NCT03309176	Phase 4	Completed	42	Evaluates whether progestin-induced endometrial withdrawal bleeding is necessary before ovulation induction with clomiphene citrate
NCT01300676	Phase 2/3	Completed	79	Tualang honey vs. hormone replacement therapy safety profile in postmenopausal women
NCT03018366	Phase 2	Completed	29	Atherosclerosis and inflammation in young women with functional hypothalamic amenorrhea (hypoestrogenemia)
NCT00392093	Phase 4	Completed	108	Hormone replacement therapy effect on disease activity, menopausal symptoms, and bone mineral density in peri/postmenopausal women with SLE
NCT06671548	Phase 3	Recruiting	120	Relugolix vs. placebo for heavy menstrual bleeding associated with uterine fibroids
NCT02792153	Phase 1	Withdrawn	0	Estradiol and fear extinction for calorie-dense foods in women with anorexia nervosa; withdrawn with zero enrollment
NCT07020429	N/A	Not Yet Recruiting	276	Traditional Chinese herbal formula (Huanjingjian decoction) for premature ovarian insufficiency

Literature Evidence

PMID	Year	Type	Journal	Key Findings
9554247	1998	RCT	Contraception	100 women with DMPA-induced amenorrhea randomized to switch to Cyclofem or continue DMPA; 82% of Cyclofem users had vaginal bleeding return within 6 months vs. 10% of DMPA continuers
38530848	2024	RCT	PLoS One	WHICH randomized trial comparing DMPA-IM vs. norethisterone enanthate effects on estradiol levels and menstrual/psychological/behavioral measures relevant to HIV risk
23641480	2013	Systematic Review	Cochrane Database of Systematic Reviews	Cochrane review of combination injectable contraceptives, including bleeding-pattern and acceptability outcomes
18843662	2008	Systematic Review	Cochrane Database of Systematic Reviews	Earlier Cochrane review of combination injectable contraceptives
6141923	1984	Review	Drug Intelligence & Clinical Pharmacy	Review of drug-induced infertility via hypothalamic-pituitary-gonadal axis or direct gonadal toxicity, including progestin effects
8725701	1996	Review	The Journal of Reproductive Medicine	Counseling framework and side-effect management for DMPA users, including amenorrhea counseling
8829701	1996	Review	International Journal of Fertility and Menopausal Studies	Review of long-acting contraceptive options and their bleeding/amenorrhea profiles
7139435	1982	Review	Canadian Medical Association Journal	Discusses whether DMPA should be considered for additional (non-contraceptive) uses
6119259	1981	Review	International Journal of Gynaecology and Obstetrics	Review of postpartum contraception, including postpartum amenorrhea considerations
120837	1979	Review	IARC Monographs on the Evaluation of Carcinogenic Risk	IARC monograph on Medroxyprogesterone Acetate

New Zealand Market Information

Medroxyprogesterone Acetate is currently not marketed in this jurisdiction (market status: 未上市), and no license records are available in this Evidence Pack.

Safety Considerations

Please refer to the package insert for safety information. Key warnings, contraindications, and drug interaction data for Medroxyprogesterone Acetate are not currently available in this Evidence Pack (regulatory package insert data collection is flagged as a Blocking data gap).

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: The mechanistic link between Medroxyprogesterone Acetate and amenorrhea is well-established pharmacology (progestin-induced endometrial atrophy), and one RCT directly investigates this indication (NCT02449161), though it was terminated. Overall evidence is directionally strong but incomplete for a full safety/efficacy package.

To proceed, the following is needed:

TFDA/regulatory package insert warnings and contraindications (currently a Blocking data gap)
Confirmed original indication and DrugBank mechanism-of-action data
Completion or replacement of the terminated NCT02449161 trial, or additional prospective data specifically on Medroxyprogesterone Acetate for amenorrhea (rather than adjacent HRT/contraception trials)
Drug interaction (DDI) data, currently unavailable ("not_found")
Disclaimer

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