Progesterone
| 證據等級: L5 | 預測適應症: 10 個 |
目錄
Progesterone: From Hormonal Therapy to Amenorrhea
One-Sentence Summary
Progesterone is a natural steroid hormone with long-established roles in reproductive endocrinology; this evidence pack does not contain a specific SAHPRA-registered indication for the drug in South Africa (it is currently not marketed here). The TxGNN model predicts it may be effective for Amenorrhea, ranked 14th among all predicted indications with a score of 99.9996%. Evidence support is currently indirect: 49 clinical trials and 18 publications were retrieved, but none is a completed trial specifically testing progesterone’s efficacy against amenorrhea — most evidence instead relates to the well-established use of progesterone/progestins for menstrual-cycle regulation and diagnostic withdrawal bleeding.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not specified in this evidence pack (no SAHPRA license/indication text available — see South Africa Market Information below) |
| Predicted New Indication | Amenorrhea |
| TxGNN Prediction Score | 99.9996% (rank 14 of all predicted indications) |
| Evidence Level | L4 |
| South Africa Market Status | Not marketed |
| Number of SAHPRA Registrations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism-of-action data is not available in this evidence pack. Based on the mechanistic rationale accompanying this prediction, progesterone acts on the hypothalamic-pituitary-ovarian (HPO) axis. The progesterone withdrawal bleeding test is a classic clinical method used to evaluate the etiology of amenorrhea, and progestogen therapy is already one of the standard interventions for secondary and anovulatory (ovulatory-disorder) amenorrhea.
This points to an important nuance for evaluators: rather than identifying a genuinely novel therapeutic application, the TxGNN model may largely be recovering progesterone’s already-established clinical role in the amenorrhea diagnostic/treatment pathway (progestin challenge test, induction of withdrawal bleeding, and progestin support in anovulatory cycles). Several of the retrieved clinical trials reinforce this — e.g., studies of medroxyprogesterone acetate and progesterone-induced withdrawal bleeding directly in amenorrhea/oligomenorrhea populations — while most of the higher-graded trials (functional hypothalamic amenorrhea, bone density, eating disorders) study the disease population rather than progesterone itself, using estrogen, romosozumab, or kisspeptin as the actual intervention.
Consequently, the reasonableness of this “prediction” rests less on discovering a new mechanism and more on confirming a known, guideline-supported use — which still has value for standardizing practice in a market where the drug is not currently registered, but should not be framed to prescribers as a novel repurposing opportunity.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01942668 | Phase 3 | Completed | 1845 | Prospective, randomized, double-blind, placebo-controlled trial of combined estradiol + progesterone for vasomotor symptoms in postmenopausal women with an intact uterus |
| NCT02449161 | Phase 3 | Terminated | 60 | RCT of post-endometrial-ablation medroxyprogesterone acetate on endometrial amenorrhea rates in women with heavy menstrual bleeding |
| NCT03309176 | Phase 4 | Completed | 42 | Evaluated whether progesterone-induced endometrial withdrawal bleeding is necessary before clomiphene-based ovulation induction in oligo-/amenorrhea |
| NCT05312190 | N/A | Unknown | 330 | Multicenter RCT comparing Zhenqi Buxue Oral Liquid, Progesterone Capsules, and their combination for menstrual disorders |
| NCT01185782 | Phase 3 | Completed | 300 | Single-blind comparative study of SJ-0021 vs. purified pituitary gonadotropin in amenorrhea I / anovulatory cycles |
| NCT06533865 | Phase 3 | Recruiting | 114 | Romosozumab as adjunct to physiologic estrogen replacement (with cyclic progesterone) for bone density in functional hypothalamic amenorrhea |
| NCT00088153 | Phase 2/3 | Completed | 110 | Effects of estrogen administration on bone development in adolescents with anorexia-nervosa-related amenorrhea |
| NCT01674426 | N/A | Completed | 17 | Randomized pilot study of cognitive behavior therapy vs. observation for functional hypothalamic amenorrhea |
| NCT03740204 | Phase 2 | Recruiting | 120 | RCT of transdermal estradiol with cyclic progesterone vs. placebo on cognitive/reward outcomes in hypoestrogenemic eating-disorder patients |
| NCT02858336 | N/A | Completed | 38 | Studied effects of caloric restriction, diet and exercise on menstrual cycles in functional hypothalamic amenorrhea |
Note: no SANCTR or PACTR-registered trials were identified in this evidence pack.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 38652231 | 2024 | Review | Reviews in Endocrine & Metabolic Disorders | Reviews diagnostic and therapeutic use of oral micronized progesterone in endocrinology, including its action on hypothalamic kisspeptin/neurokinin B/dynorphin neurons regulating LH/FSH |
| 35525789 | 2022 | Review | Current Problems in Pediatric and Adolescent Health Care | Reviews etiology and management of amenorrhea in adolescent/young adult women, centered on hypothalamic-pituitary-ovarian axis dysfunction |
| 8629565 | 1996 | Review | American Family Physician | Practical evaluation approach to amenorrhea, noting progesterone challenge as a key diagnostic step after ruling out pregnancy |
| 33716979 | 2021 | Review | Frontiers in Endocrinology | Reviews etiology, symptomatology and treatment (including hormone therapy) for premature ovarian insufficiency, a cause of secondary amenorrhea |
| 28257537 | 2017 | Review | Southern Medical Journal | Current concepts in primary ovarian insufficiency, including hormone replacement for resulting amenorrhea |
| 22283375 | 2012 | Review | Gynecological Endocrinology | Describes neuroendocrine control of ovulation and how HPO axis failure results in anovulation/amenorrhea |
| 18756412 | 2008 | Review | Seminars in Reproductive Medicine | Reviews intrauterine adhesions (Asherman’s syndrome) presenting across a spectrum from amenorrhea to menstrual disturbance |
| 945033 | 1976 | Case series | Annals of Internal Medicine | Studied 15 patients with galactorrhea-amenorrhea syndromes, noting failure of luteinizing hormone and progesterone levels to show ovulatory/luteal patterns |
| 5388335 | 1969 | Review | Clinical Obstetrics and Gynecology | Early general review of amenorrhea (abstract not available) |
| 35463307 | 2022 | Meta-analysis | Frontiers in Oncology | Meta-analysis of risk factors and prognostic significance of chemotherapy-induced amenorrhea in premenopausal breast cancer patients |
South Africa Market Information
No SAHPRA product registrations were found for progesterone in this evidence pack (market status: not marketed, total licenses: 0). Prescribers should confirm current registration status directly with SAHPRA before considering clinical use, as unregistered products require Section 21 authorization for access in South Africa.
Safety Considerations
Please refer to the SAHPRA-approved Professional Information (PI) for safety information. Report adverse drug reactions to SAHPRA.
(Note: this evidence pack flagged a Blocking data gap — TFDA/SAHPRA label warnings and contraindications are not yet available — which by itself prevents a full safety pre-assessment (S1) for this candidate.)
Conclusion and Next Steps
Decision: Hold
Rationale:
- No completed trial in this pack directly tests progesterone’s efficacy specifically for treating amenorrhea (evidence level L4, mechanistic/indirect); most higher-relevance trials study the disease population using other interventions (estrogen, romosozumab, kisspeptin).
- The drug is not currently registered in South Africa (0 SAHPRA licenses), and a Blocking data gap on label warnings/contraindications prevents safety pre-assessment.
- The predicted indication substantially overlaps with progesterone’s already-established diagnostic/therapeutic role in amenorrhea (progestin challenge test, withdrawal bleeding induction), so the incremental value of this “prediction” needs to be clarified before any development effort is prioritized.
To proceed, the following is needed:
- SAHPRA-approved Professional Information (PI): warnings, contraindications, and drug interaction data (currently a Blocking gap)
- Confirmed mechanism-of-action documentation (DrugBank or equivalent)
- A clinical/regulatory assessment of whether this represents a genuinely new therapeutic use, or codification of existing off-label/diagnostic practice
- If pursued, a targeted trial or registry data directly evaluating progesterone (not estrogen/other progestins) as treatment for amenorrhea subtypes
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.