Medroxyprogesterone Acetate

證據等級: L5

預測適應症: 10 個

Medroxyprogesterone Acetate: From Hormonal Contraception/Menstrual Disorder Management to Amenorrhoea

One-Sentence Summary

Medroxyprogesterone acetate (MPA) is a synthetic progestogen long used as a contraceptive (oral and depot injection) and for managing menstrual disorders. The TxGNN model predicts it may be effective for amenorrhoea, a use that is largely already recognised in existing pharmacology rather than a novel discovery, with 10 clinical trials and 20 publications currently identified as supporting evidence.

Quick Overview

Item	Content
Original Indication	Not available from this Evidence Pack (0 ARTG entries); MPA is generally known for contraception (oral/depot injection) and management of secondary amenorrhoea/abnormal uterine bleeding
Predicted New Indication	Amenorrhoea (disease)
TxGNN Prediction Score	99.9994%
Evidence Level	L2
Australia Market Status	Not Marketed
Number of ARTG Entries	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Detailed mechanism of action data was not returned by DrugBank for this drug. Based on well-established pharmacology, medroxyprogesterone acetate is a synthetic progestogen (progesterone-receptor agonist), available as an oral tablet and as a long-acting depot injection (DMPA). It suppresses the hypothalamic–pituitary–ovarian axis (inhibiting GnRH/LH pulsatility) and induces endometrial atrophy/decidualisation — the basis for its long-standing clinical use in inducing withdrawal bleeding, treating secondary amenorrhoea and abnormal uterine bleeding, and providing long-acting contraception.

Amenorrhoea is therefore not a truly novel indication for MPA: it is mechanistically continuous with the drug’s known progestogenic effects. MPA is used therapeutically to manage amenorrhoea/abnormal bleeding, and at contraceptive doses (DMPA) commonly causes amenorrhoea as an expected on-therapy effect. The evidence pack’s own rationale flags this directly — describing the mechanism as “textbook-level” for MPA and closer to reinforcement of an existing indication than a new repurposing hypothesis.

The strongest single trial (NCT02449161, Phase 3) directly tested post-ablation MPA for endometrial amenorrhoea rates, but it was terminated with a small sample (n=60), limiting definitive conclusions. Supporting literature spans DMPA-induced amenorrhoea management and endometrial/hormonal correlates, consistent with this mechanistic picture.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrolment	Key Findings
NCT02792153	Phase 1	Withdrawn	0	Estradiol and fear extinction for calorie-dense foods in weight-restored anorexia nervosa; withdrawn, no enrolment — limited relevance
NCT07020429	N/A	Not yet recruiting	276	Chinese herbal formula (Huanjingjian decoction) for premature ovarian insufficiency; no MPA arm
NCT03309176	Phase 4	Completed	42	Tested whether progesterone-induced withdrawal bleeding is necessary before ovulation induction in women with oligo-/amenorrhoea
NCT00808132	Phase 3	Completed	1886	Large RCT of bazedoxifene/conjugated estrogens for menopausal symptoms, endometrial protection and osteoporosis prevention
NCT03018366	Phase 2	Completed	29	Functional hypothalamic amenorrhoea and cardiovascular risk markers associated with low-estrogen states
NCT00392093	Phase 4	Completed	108	HRT effects on disease activity, menopausal symptoms and bone mineral density in peri/postmenopausal women with SLE
NCT02449161	Phase 3	Terminated	60	Direct test of post-ablation MPA on endometrial amenorrhoea rates — most directly relevant trial, but terminated early with small sample
NCT01300676	Phase 2/3	Completed	79	Tualang honey vs HRT safety profile in postmenopausal women
NCT06671548	Phase 3	Recruiting	120	Relugolix vs placebo for heavy menstrual bleeding associated with uterine fibroids
NCT01463202	Phase 4	Completed	184	Timing of postpartum DMPA administration and its effect on breastfeeding continuation, contraceptive continuation and postpartum depression

No ANZCTR (Australian New Zealand Clinical Trials Registry) entries were identified for this indication.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
38530848	2024	RCT	PLoS One	WHICH randomised trial comparing DMPA-IM and NET-EN effects on estradiol levels, mood, sexual activity and menstrual patterns relevant to HIV risk
9554247	1998	RCT	Contraception	Women with DMPA-induced amenorrhoea randomised to switch to Cyclofem or continue DMPA; 82% resumed bleeding on Cyclofem vs 10% on DMPA
23641480	2013	Systematic Review (Cochrane)	Cochrane Database Syst Rev	Review of combination injectable contraceptives’ efficacy and acceptability
842303	1977	Comparative Study	Acta Obstet Gynecol Scand	Endometrial histology and circulating MPA/estradiol/gonadotropin levels compared between MPA-induced and secondary amenorrhoea
8725701	1996	Review	J Reprod Med	Counselling framework and management of DMPA side effects, including amenorrhoea
6141923	1984	Review	Drug Intell Clin Pharm	Review of drug-induced infertility via hypothalamic-pituitary-gonadal axis effects, including progestogens
6119259	1981	Review	Int J Gynaecol Obstet	Postpartum contraception review, including timing relative to postpartum amenorrhoea
120837	1979	Review	IARC Monographs	Pharmacological/toxicological monograph on medroxyprogesterone acetate
8492647	1993	Review	MCN Am J Matern Child Nurs	Overview of Depo-Provera (DMPA) clinical use
12222332	1991	Review	Entre Nous	Overview of once-a-month estrogen/progestogen injectable contraceptives

Australia Market Information

MPA currently has no ARTG (Australian Register of Therapeutic Goods) entries in this Evidence Pack — market status is recorded as Not Marketed, with 0 registered licences.

Safety Considerations

Please refer to the TGA-approved Product Information (PI) for safety information. No key warnings, contraindications or drug interaction data were available in this Evidence Pack.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: The mechanistic case is strong and well-established (MPA’s progestogenic suppression of the HPO axis and endometrial effects already underpin its known role in amenorrhoea/abnormal bleeding management), and evidence level reaches L2. However, this is offset by the absence of Australian market presence (0 ARTG entries), missing MOA confirmation, and a Blocking data gap on TFDA/PI warnings and contraindications, which prevents a full safety assessment.

To proceed, the following is needed:

TGA-approved Product Information (warnings, contraindications) — currently a Blocking data gap
Confirmed mechanism of action detail from DrugBank
Clarification of MPA’s current registration status in Australia, given 0 ARTG entries
Follow-up on the terminated NCT02449161 trial or a replacement adequately powered study, since it is the only trial directly testing MPA for amenorrhoea
Disclaimer

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