Medroxyprogesterone Acetate

證據等級: L5

預測適應症: 10 個

Medroxyprogesterone Acetate: From Hormonal Contraception to Amenorrhea

One-Sentence Summary

Medroxyprogesterone acetate (MPA, DrugBank DB00603) is a synthetic progestin most widely known as a depot injectable contraceptive (e.g., Depo-Provera) and menstrual-cycle regulator. The TxGNN model predicts it may also be effective for treating Amenorrhea, with 10 clinical trials and 20 publications currently identified as supporting evidence, including a Phase 3 RCT that directly evaluated post-ablation MPA for endometrial amenorrhea.

Quick Overview

Item	Content
Original Indication	Hormonal contraception (depot injectable, e.g. Depo-Provera) — inferred from literature evidence; not documented in the South Africa regulatory dataset
Predicted New Indication	Amenorrhea
TxGNN Prediction Score	99.99%
Evidence Level	L2
South Africa Market Status	Not marketed
Number of SAHPRA Registrations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Detailed mechanism-of-action data is not available in the evidence pack (Data Gap DG002). Based on well-established pharmacology, medroxyprogesterone acetate is a synthetic progestin that suppresses hypothalamic-pituitary-gonadal axis signalling (reducing GnRH/LH pulsatility) and acts directly on the endometrium, driving secretory transformation and eventual atrophy/shedding of the endometrial lining.

This is the same mechanism already exploited when MPA is used as a depot contraceptive: a very high proportion of long-term DMPA users develop treatment-induced amenorrhea as a recognised pharmacological effect, a phenomenon documented in the literature for decades (e.g., PMID 842303, PMID 9554247). In other words, “amenorrhea” is not a biologically novel target for MPA — it is a direct, mechanistically predictable extension of an effect the drug already produces in its established contraceptive use, now being considered as a deliberate therapeutic endpoint (e.g., managing heavy menstrual bleeding, post-ablation bleeding control, or endometrial suppression).

This is further supported by NCT02449161, a Phase 3 RCT that directly assessed post-ablation MPA on endometrial amenorrhea rates, though the trial was terminated early with a small enrollment (n=60), which tempers the strength of the direct clinical evidence. Combined with the broad, decades-long real-world experience of MPA-induced amenorrhea in contraceptive populations, the mechanistic plausibility of this prediction is high, even though confirmatory large-scale RCTs specifically targeting amenorrhea as a primary therapeutic endpoint (rather than a contraceptive side effect) remain limited.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT02449161	Phase 3	Terminated	60	RCT evaluating the effect of post-endometrial-ablation MPA on endometrial amenorrhea rates in women with heavy menstrual bleeding; terminated early.
NCT03309176	Phase 4	Completed	42	Assessed whether progesterone-induced withdrawal bleeding is necessary before ovulation induction with clomiphene citrate in women with oligo-/amenorrhea.
NCT07020429	N/A	Not yet recruiting	276	RCT of a traditional Chinese herbal formula (Huanjingjian decoction) for premature ovarian insufficiency; not an MPA trial, disease-area overlap only.
NCT06671548	Phase 3	Recruiting	120	Double-blind, placebo-controlled study of relugolix for heavy menstrual bleeding associated with uterine fibroids; MPA-specific relevance unconfirmed.
NCT00392093	Phase 4	Completed	108	Hormone replacement therapy effects on disease activity, menopausal symptoms and bone mineral density in peri/postmenopausal women with SLE.
NCT02792153	Phase 1	Withdrawn	0	Estradiol and fear-extinction study in weight-restored women with anorexia nervosa; withdrawn (enrollment 0), low relevance.
NCT01463202	Phase 4	Completed	184	Timing of postpartum depot MPA administration and its effect on breastfeeding continuation, contraceptive continuation, and postpartum depression.
NCT03018366	Phase 2	Completed	29	Compared cardiovascular risk markers in young women with functional hypothalamic amenorrhea versus regularly cycling controls.
NCT01300676	Phase 2/3	Completed	79	Safety profile of Tualang honey combined with hormone replacement therapy in postmenopausal women.
NCT00808132	Phase 3	Completed	1886	Large RCT of bazedoxifene/conjugated estrogens on endometrial hyperplasia and osteoporosis prevention in postmenopausal women.

No South African National Clinical Trials Register (SANCTR) or Pan African Clinical Trials Registry (PACTR) entries were identified for this indication.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
38530848	2024	Cohort (RCT)	PLoS ONE	WHICH randomized trial: effects of DMPA vs. norethisterone enanthate on estradiol levels and menstrual/psychological/behavioural measures relevant to HIV risk.
9554247	1998	Clinical Trial	Contraception	Randomized comparison showing Cyclofem restored bleeding in 82% of women with DMPA-induced amenorrhea vs. 10% continuing DMPA.
842303	1977	Observational	Acta Obstet Gynecol Scand	Endometrial histology and hormone levels in women with MPA-induced amenorrhoea compared with women with secondary amenorrhoea.
23641480	2013	Systematic Review	Cochrane Database Syst Rev	Cochrane review of combination injectable contraceptives, including bleeding-pattern effects.
8725701	1996	Review	J Reprod Med	Counseling and management of side effects, including amenorrhea, in women using depot MPA contraception.
8492647	1993	Review	MCN Am J Matern Child Nurs	Overview of Depo-Provera use, mechanism, and menstrual effects.
120837	1979	Review	IARC Monographs	General monograph on medroxyprogesterone acetate pharmacology and use.
6119259	1981	Review	Int J Gynaecol Obstet	Postpartum contraception review, including postpartum amenorrhea considerations.
1604074	1992	Review	Rev Med Liege	General review of hormonal contraception.
6141923	1984	Review	Drug Intell Clin Pharm	Review of drug-induced infertility, including progestin-related mechanisms.

South Africa Market Information

Medroxyprogesterone acetate currently has no SAHPRA product registrations on record, and the regulatory dataset lists its South African market status as Not marketed. No dosage-form, brand-name, or Essential Medicines List (EML) inclusion data is available for this evidence pack at this time.

Safety Considerations

Please refer to the SAHPRA-approved Professional Information (PI) for safety information. Report adverse drug reactions to SAHPRA.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale:

The prediction is mechanistically well-grounded: MPA-induced amenorrhea is an established, decades-documented pharmacological effect in contraceptive use, and one directly relevant Phase 3 RCT (NCT02449161, though terminated early with n=60) supports its intentional use for endometrial amenorrhea. This corresponds to Evidence Level L2, sufficient to move past pure model prediction but short of confirmatory large-scale trial evidence.

To proceed, the following is needed:

TFDA/SAHPRA-equivalent Professional Information (PI) warnings and contraindications (currently a Blocking data gap — DG001), required before any S1 safety pre-assessment can proceed
Detailed mechanism-of-action documentation from DrugBank (High-priority data gap — DG002)
SAHPRA registration or market-entry pathway assessment, since MPA currently has zero registrations and is not marketed in South Africa
A confirmatory, adequately powered Phase 2/3 RCT specifically targeting amenorrhea as a primary therapeutic endpoint (rather than as a contraceptive side effect)
Clarification of the full trial design/title for NCT06671548 and NCT00808132, whose relevance to MPA specifically could not be confirmed from truncated records
Disclaimer

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