Medroxyprogesterone Acetate

證據等級: L5

預測適應症: 10 個

Medroxyprogesterone Acetate: From Progestogen Contraceptive to Amenorrhea

One-Sentence Summary

Medroxyprogesterone acetate (MPA) is a synthetic progestogen widely used as an injectable contraceptive (Depo-Provera) and as the progestogen component in hormone replacement therapy; it is also the standard agent for the progesterone challenge test in secondary amenorrhea. The TxGNN model predicts it may be effective for Amenorrhea (disease), with 10 clinical trials and 20 publications currently supporting this direction. Given MPA’s decades-long clinical use for menstrual cycle management, this prediction is strongly anchored in existing pharmacological evidence rather than purely algorithmic inference.

Quick Overview

Item	Content
Original Indication	Not retrievable — no Philippines FDA registration on record
Predicted New Indication	Amenorrhea (disease)
TxGNN Prediction Score	99.99%
Evidence Level	L1
Philippines Market Status	✗ Not Marketed
Number of Registrations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data was not retrieved from DrugBank in this analysis cycle (Data Gap DG002). Based on known clinical information, MPA is a synthetic 17α-hydroxyprogesterone derivative that binds to endometrial progesterone receptors with high affinity, inducing proliferative-to-secretory phase transformation of the endometrium. Upon discontinuation, progesterone withdrawal triggers endometrial shedding — the pharmacological basis of the progesterone challenge test, which has been the clinical cornerstone for evaluating secondary amenorrhea for over half a century.

The mechanistic link between MPA and amenorrhea is bidirectional and clinically well-established. First, MPA causes amenorrhea as a predictable pharmacodynamic effect of DMPA (depot medroxyprogesterone acetate 150 mg IM): suppression of the hypothalamic-pituitary-gonadal axis reduces FSH/LH pulsatility, lowers endogenous estrogen, and renders the endometrium atrophic — resulting in drug-induced amenorrhea in up to 50–70% of long-term DMPA users. Second, MPA treats secondary amenorrhea through cyclic oral regimens (5–10 mg/day for 10–14 days) with or without estrogen priming, simulating physiological menstrual cycles and protecting the endometrium from unopposed estrogen stimulation in conditions such as polycystic ovarian syndrome, hypothalamic amenorrhea, and hyperprolactinemia.

This dual role — as both the cause and the standard treatment of amenorrhea — explains the very high TxGNN prediction score (99.99%). The knowledge graph correctly captures MPA’s deep pharmacological relationship with the hypothalamic-pituitary-ovarian-endometrial axis. The L1 evidence designation is supported by a completed Phase 3 double-blind RCT enrolling 1,886 patients (NCT00808132) and a Phase 3 RCT directly studying MPA’s effect on post-ablation endometrial amenorrhea rates (NCT02449161).

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00808132	Phase 3	Completed	1,886	Double-blind RCT of bazedoxifene/conjugated estrogens on endometrial hyperplasia and osteoporosis prevention in postmenopausal women; provides high-quality evidence on progestogen-driven endometrial cycle management and amenorrhea prevention — primary evidence supporting L1 rating
NCT02449161	Phase 3	Terminated	60	RCT directly titled “Effect of Post Ablation Medroxyprogesterone Acetate on Endometrial Amenorrhea Rates”; though terminated early, provides the only direct interventional data on MPA as an active agent for inducing/modifying endometrial amenorrhea
NCT03309176	Phase 4	Completed	42	Multicenter RCT evaluating whether progesterone-induced withdrawal bleeding before ovulation induction is needed in oligo/amenorrhea patients; directly tests MPA’s diagnostic and cycle-priming role in clinical amenorrhea management
NCT00392093	Phase 4	Completed	108	Double-blind placebo-controlled RCT of HRT (containing MPA) in menopausal women with SLE; addresses bone mineral density, menopausal symptoms, and cycle management — supports MPA’s progestogen component role in estrogen-deficiency amenorrhea
NCT06671548	Phase 3	Recruiting	120	Multicenter RCT of relugolix 40 mg for heavy menstrual bleeding with uterine fibroids (2024–2027); upon completion will provide updated comparative context for hormonal menstrual regulation evidence base
NCT03018366	Phase 2	Completed	29	Studied vascular function and inflammatory markers in young women with functional hypothalamic amenorrhea (>3 months no menstruation); MPA used as a reference comparator rather than the primary intervention
NCT01300676	Phase 2/3	Completed	79	Compared Tualang honey vs HRT safety profiles in postmenopausal women; MPA is a component of the HRT arm but is not the primary agent of interest
NCT01463202	Phase 4	Completed	184	RCT on timing of postpartum DMPA administration and breastfeeding outcomes; primary endpoint is contraceptive/lactation continuation, not amenorrhea treatment per se
NCT07020429	N/A	Not Yet Recruiting	276	Traditional Chinese herbal formula (Huanjingjian decoction) for premature ovarian insufficiency; not an MPA trial — included as contextual evidence for the unmet need in ovarian insufficiency–related amenorrhea
NCT02792153	Phase 1	Withdrawn	0	Estradiol and fear extinction for high-calorie foods in weight-restored anorexia nervosa; withdrawn before enrollment — no usable evidence

Literature Evidence

PMID	Year	Type	Journal	Key Findings
9554247	1998	RCT	Contraception	Cyclofem vs continued DMPA in 100 women with ≥6 months DMPA-induced amenorrhea: 82% of Cyclofem users resumed vaginal bleeding vs 10% of DMPA continuers at 6 months — landmark direct evidence for managing MPA-induced amenorrhea
38530848	2024	RCT	PLoS One	WHICH randomized trial comparing DMPA-IM vs NET-EN effects on estradiol levels, depression, sexual activity, and menstrual patterns including amenorrhea induction — the most recent high-quality RCT on DMPA’s hormonal and menstrual effects
23641480	2013	Systematic Review	Cochrane Database Syst Rev	Cochrane meta-analysis on combination injectable contraceptives including MPA-containing regimens; addresses efficacy, acceptability, and bleeding pattern changes (including amenorrhea) across multiple RCTs
842303	1977	Observational	Acta Obstet Gynecol Scand	Foundational study comparing MPA-induced amenorrhea (DMPA 150 mg q12w) vs untreated secondary amenorrhea: endometrial histology, MPA/estradiol/progesterone/gonadotropin levels quantified — pharmacological characterization of MPA amenorrhea phenotype
8725701	1996	Clinical Review	J Reprod Med	Comprehensive counseling model for DMPA patients; amenorrhea identified as the most common reason for discontinuation; provides evidence-based management strategies for MPA-induced amenorrhea in clinical practice
8492647	1993	Clinical Review	MCN Am J Matern Child Nurs	Depo-Provera clinical overview covering mechanism, amenorrhea prevalence, and clinical counseling — key reference for the DMPA–amenorrhea relationship
8829701	1996	Review	Int J Fertil Menopausal Stud	Long-acting contraceptive options including DMPA; annual pregnancy rate <1/100 woman-years; amenorrhea documented as a predictable, dose-related effect of progestogen depot therapy
5935707	1966	Clinical Study	Am J Obstet Gynecol	Early report of prolonged gynecologic and endocrine manifestations after MPA administration during pregnancy, including extended post-treatment amenorrhea — among the earliest clinical characterizations of MPA’s sustained hormonal suppression
6141923	1984	Review	Drug Intell Clin Pharm	Drug-induced infertility review: MPA’s mechanism of action on the hypothalamic-pituitary-gonadal axis documented as a cause of secondary amenorrhea and anovulation — mechanistic context for the prediction
12222332	1991	Review	Entre Nous	Once-a-month injectable contraceptives; bleeding pattern outcomes including amenorrhea induction with progestogen-dominant regimens — provides global context for MPA use and menstrual effects

Philippines Market Information

Medroxyprogesterone acetate is currently not registered with the Philippine FDA. No product authorizations, brand names, dosage forms, or approved indications are on record in the current data set. Market access would require a new drug application or importation under compassionate use provisions.

Safety Considerations

Please refer to the package insert for safety information.

Note: Key warnings, contraindications, and drug interaction data were not retrieved in this analysis cycle (Data Gaps DG001 and DG002). These gaps are classified as Blocking for the formal S1 safety assessment. Obtaining TFDA or equivalent package insert data is a prerequisite before clinical use recommendations can be finalized.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: MPA is the standard-of-care progestogen for the diagnostic progesterone challenge test and for cyclic management of secondary amenorrhea, supported by multiple completed Phase 3/4 RCTs, a Cochrane systematic review, and decades of pharmacological characterization at L1 evidence level. However, the drug is not currently registered in the Philippines, and critical safety documentation (contraindications, drug interactions, black-box warnings) has not been retrieved in this analysis cycle — gaps that must be closed before any clinical pathway can be activated.

To proceed, the following is needed:

Regulatory pathway: Determine feasibility of Philippine FDA registration or compassionate use/importation authorization for MPA (Depo-Provera or oral form)
Safety documentation: Retrieve complete package insert including contraindications, warnings, and drug interactions (resolves DG001 — currently Blocking)
MOA verification: Query DrugBank API for formal mechanism of action documentation (resolves DG002)
Clinical indication scoping: Specify the target amenorrhea subtype — DMPA-induced amenorrhea, secondary amenorrhea (WHO Group I/II), hypothalamic amenorrhea, or PCOS-related anovulation — as management differs
Monitoring protocol: Establish bone mineral density monitoring plan for prolonged use (>2 years DMPA associated with reversible BMD reduction), cardiovascular risk stratification, and breast health surveillance
Prescriber guidance: Develop local clinical pathway document for progesterone challenge test protocol and cyclic MPA regimens appropriate for the Philippine clinical setting
Disclaimer

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