Repurposing candidates

Meta-analytic and umbrella-review evidence in postmenopausal women shows MHT effectively reduces vasomotor symptom frequency (RR 0.43) and severity (RR 0.29) and lowers fracture risk (RR 0.72), with additional cardiovascular benefit (improved FMD) when started within 10 years of menopause.

Systematic review and review evidence indicate citalopram reduces the frequency and severity of menopausal vasomotor symptoms by approximately 40-65%.

Review-level evidence indicates desvenlafaxine reduces the frequency and severity of menopausal vasomotor symptoms by roughly 40-65%.

Escitalopram reduces the frequency and severity of menopausal vasomotor symptoms (hot flashes) by approximately 40% to 65% according to review-level evidence.

Systematic review and review evidence indicate paroxetine reduces the frequency (approximately 40-65%) and severity of menopausal vasomotor symptoms.

Venlafaxine is reported in a systematic review and review articles to effectively reduce the frequency and severity of menopausal vasomotor symptoms (hot flashes), with frequency reductions of approximately 40% to 65%.

CEE (with or without MPA) is associated with an increased risk of stroke and venous thromboembolism, on the order of about 1 excess event per 1000 person-years.

Combined CEE plus MPA therapy in menopausal women is associated with an increased breast cancer risk of approximately 1 excess event per 1000 person-years compared with placebo.

A review reports that systemic estrogen combined with a progestogen reduces the frequency of menopausal vasomotor symptoms by approximately 75%.

An umbrella review found intravaginal estrogen therapy beneficial for vaginal atrophy, a menopausal condition.

A review concludes that hormonal treatments are efficacious for women with bothersome menopausal vasomotor and genitourinary (GSM) symptoms.

A review reports that low-dose vaginal estrogen subjectively improves genitourinary syndrome of menopause symptom severity by approximately 60% to 80%.

A systematic review and meta-analysis describes menopause hormone therapy as an effective method to alleviate menopause-related symptoms in women.

A review reports that oral ospemifene improves genitourinary syndrome of menopause symptom severity by approximately 30% to 50%.

A systematic review reports that SSRI/SNRIs can reduce menopausal hot flashes by 65% with onset within the first week.

A systematic review reports that SSRIs/SNRIs can reduce menopausal hot flashes by up to 65%, with onset of benefit within the first week.

CEE with or without MPA were the only menopausal hormonal treatments with clinical trials specifically designed to assess cardiovascular events, VTE, and breast cancer risk.

A clinical review reports that systemic estrogen reduces menopausal vasomotor symptom frequency by approximately 75% and is first-line therapy for vasomotor and GSM symptoms.

A systematic review and meta-analysis in postmenopausal women found that combined estrogen-progesterone therapy did not alter cardiovascular endpoint outcomes compared with estrogen-only therapy.

A systematic review and meta-analysis found no difference in cardiovascular endpoints between estrogen monotherapy and estrogen-progesterone combination therapy in postmenopausal women.

An umbrella review reported EPT to be associated with harm for lung cancer mortality in menopausal women.

A systematic review found fluoxetine appears less effective for menopausal vasomotor symptoms and should be considered a second-line treatment option.

A review reports that gabapentin reduces the frequency of menopausal vasomotor symptoms by approximately 40% to 65%.

A clinical review reports that vaginal prasterone improves genitourinary syndrome of menopause symptom severity by approximately 40% to 80%.

A systematic review found sertraline less effective for menopausal vasomotor symptoms and recommended it as a second-line option.

A systematic review evaluated the efficacy and tolerability of SSRI/SNRIs for treating vasomotor symptoms in menopausal women, but no specific outcome magnitudes are provided in the verified claims.

BAZEDOXIFENE is a phase-3 clinical candidate for menopause acting as an estrogen receptor modulator targeting estrogen receptor 2.

Estradiol valerate is an approved clinical agent for menopause acting as an estrogen receptor alpha (ESR1) agonist.

A review states that bioidentical estrogens are available to treat menopausal vasomotor symptoms.

An umbrella review reports that estrogen therapy was beneficial for cardiovascular mortality in menopausal women.

A clinical review states that nonhormonal options are among the efficacious treatments for bothersome menopausal vasomotor and GSM symptoms.

A single user reported that one year of HRT including testosterone reversed their severe osteoporosis.

Estradiol is an approved estrogen receptor alpha (ESR1) agonist indicated for menopause.

Per an Open Targets annotation, RALOXIFENE is a Phase 2 clinical candidate for menopause acting as an estrogen receptor beta modulator on estrogen receptor 2 (ESR2).

Per an Open Targets annotation, synthetic conjugated estrogens, B is an approved estrogen receptor agonist (ESR2) indicated for menopause.

A study is assessing the efficacy of repeated G-CSF administration for hot flashes and vasomotor symptoms in postmenopausal women, but no efficacy results are reported.

A single user reported creatine had no effect on menopause-related brain fog until the dosage was substantially increased.

A single community account reports that vaginal estrogen resolved their bladder issues, consistent with genitourinary symptoms of menopause.

Desvenlafaxine succinate is a Phase 3 clinical candidate for menopause acting via serotonin transporter (SLC6A4) inhibition per Open Targets.

Per Open Targets, estriol is a Phase 2 clinical candidate for menopause acting as an estrogen receptor modulator on estrogen receptor 2.

Per Open Targets, LEUPROLIDE is a Phase 1 clinical candidate for menopause acting as a gonadotropin-releasing hormone receptor agonist.

Per Open Targets, NORETHINDRONE is a Phase 3 clinical candidate for menopause acting as a progesterone receptor agonist.

A systematic review notes that patient response to drugs for menopausal hot flashes is variable, without quantifying efficacy.

Per Open Targets, SMC021 is a calcitonin receptor agonist that reached Phase 2 clinical development for menopause.

A single source asserts that emerging evidence supports the efficacy of non-pharmacological and non-hormonal treatments for menopause when hormone therapy is contraindicated or avoided.

A single narrative source states that vaginal oestrogen appears safe for most patients with genitourinary symptoms.

Per Open Targets, red clover is registered as a Phase 1 clinical candidate for menopause, but no mechanistic data are provided.

ISOFLAVONE is listed as a Phase 3 clinical candidate for menopause per Open Targets, but no mechanistic or outcome data are provided.

Per an Open Targets registry entry, NITRIC ACID is listed as a Phase 2 clinical candidate for menopause, with no mechanistic detail provided.

Pterostilbene is listed in Open Targets as a clinical candidate for menopause, but no mechanistic or clinical-stage detail is provided.

A systematic review/meta-analysis and a comparative treatment study indicate D-chiro-inositol provides benefits for some metabolic measures, ovulation, menstrual regularity, and insulin resistance in PCOS patients.

A guideline-informing systematic review and meta-analysis plus independent studies indicate myo-inositol improves metabolic measures, menstrual regularity, and insulin resistance in PCOS patients.

In infertile women with PCOS, letrozole was associated with higher ovulation rates and greater likelihood of live birth and singleton pregnancy compared with clomiphene citrate.

A systematic review and meta-analysis of RCTs found anti-androgens may mitigate hyperandrogenism-related symptoms of PCOS but are not preferred over combined oral contraceptives except when COCPs are contraindicated, poorly tolerated, or inadequately effective.

A meta-analysis of RCTs found anti-androgens plus lifestyle superior to metformin plus lifestyle for hirsutism and SHBG in PCOS, but not superior to placebo plus lifestyle for those outcomes.

A systematic review and meta-analysis of RCTs found that adding anti-androgens to metformin + lifestyle lowered testosterone in PCOS, though hirsutism did not differ between combinations.

A systematic review and meta-analysis found COCP inferior to combination treatment for FAI and SHBG in PCOS, with no difference in testosterone.

A systematic review and meta-analysis of RCTs indicates combined oral contraceptive pills may reduce hyperandrogenism-related symptoms in women with PCOS.

In meta-analyses informing the 2023 PCOS guidelines, metformin may improve waist-hip ratio and hirsutism versus inositol but is inferior to combined oral contraceptives on androgen markers (FAI, SHBG, testosterone) in women with PCOS.

A systematic review and meta-analysis reports that combined metformin and COCP treatment provides some biochemical benefits by targeting both hyperinsulinemia and hyperandrogenism in PCOS.

A systematic review and meta-analysis of RCTs found that adding anti-androgens to COCP produced no differences in other outcomes compared with COCP alone in women with PCOS.

A systematic review and meta-analysis found COCP was inferior to combination treatment for insulin and insulin resistance in PCOS, but showed no difference in hirsutism versus metformin or combination treatment.

A systematic review and meta-analysis of RCTs found that daily dosing was more effective than every-three-day dosing for hirsutism and produced lower androstenedione levels in women with PCOS.

A systematic review/meta-analysis informing the 2023 PCOS guidelines found the evidence for inositol in PCOS limited and inconclusive, with efficacy indeterminate, though one comparison review described it as useful for endocrine-metabolic disorders.

GONADOTROPIN, CHORIONIC is an early-phase (EARLY_PHASE_1) clinical candidate for PCOS acting as a luteinizing hormone/choriogonadotropin receptor agonist per Open Targets.

A single study reports that combined oral contraceptives effectively reduce circulating androgens in women with PCOS.

In a single small follow-up study of lean PCOS teenagers, myo-inositol combined with oral contraceptives prevented increases in weight and BMI and improved metabolic and hormonal parameters.

A single follow-up comparison study suggests that a natural compound (Myo-Inositol) combined with OCP improves metabolic and hormonal parameters in PCOS adolescents.

Ganirelix acetate is listed as an early-phase clinical candidate for PCOS acting as a gonadotropin-releasing hormone receptor antagonist per Open Targets.

Pavinetant is a Phase 2 small-molecule clinical candidate for PCOS that acts as a Neurokinin 3 receptor (TACR3) antagonist.

Simvastatin is a Phase 3 clinical candidate for PCOS acting via inhibition of HMG-CoA reductase.

A single PCOS pregnancy trial suggests clomiphene citrate is more likely than letrozole to result in first-trimester intrauterine fetal demise.

A single source proposes D-chiro inositol as a potentially valid therapeutic approach for treating patients with PCOS.

ERGOCALCIFEROL is annotated as a vitamin D receptor agonist and a Phase 2 clinical candidate for PCOS per Open Targets.

Estradiol valerate is listed as an early-phase clinical candidate for PCOS acting as an estrogen receptor alpha (ESR1) agonist.

Per Open Targets, gonadorelin acetate is a Phase 3 clinical candidate for PCOS acting as a GnRH receptor agonist on the gonadotropin releasing hormone receptor.

Menotropins is listed in Open Targets as a Phase 2/3 clinical candidate for PCOS acting as a follicle stimulating hormone receptor agonist on the FSH receptor.

Mazdutide is being studied for efficacy in obese female adults with PCOS, but no results are reported.

A single follow-up comparison study suggests myo-inositol alone improves metabolic and hormonal parameters in PCOS adolescents.

CORTICOTROPIN is listed by Open Targets as an early-phase (EARLY_PHASE_1) clinical candidate for PCOS acting as a melanocortin 2 receptor agonist.

A single systematic review notes that the safety of anti-androgen treatments in PCOS remains unclear because prior reviews focused on non-PCOS populations.

Acetylcysteine is listed as a Phase 2/3 clinical candidate for PCOS per Open Targets, but no mechanistic detail is provided.

Enclomiphene citrate is listed in Open Targets as a Phase 3 clinical candidate for PCOS.

Per Open Targets, folic acid is registered as a Phase 1/2 clinical candidate for PCOS, but no mechanistic detail is provided.

Per Open Targets, KISSPEPTIN-10 is listed as a Phase 1 clinical candidate for PCOS, but no mechanistic data are provided.

TILDACERFONT is listed as a Phase 2 clinical candidate small molecule for PCOS per Open Targets, with no mechanistic detail provided.

Per Open Targets, ubidecarenone is a phase 2/3 clinical candidate for PCOS, but no mechanistic pathway evidence is provided.

A systematic review (including three RCTs) found that aromatase inhibitors combined with progestogens or oral contraceptives reduce endometriosis-related pain severity and improve quality of life.

A systematic review reports that 6 months of aromatase inhibitors plus a GnRH analogue after surgery reduces endometriosis recurrence risk compared with GnRH analogue alone.

A randomized clinical trial found that combined oral contraceptives improved endometriosis-associated pain and health-related quality of life (EHP-30) in women with endometriosis.

A single systematic review reports that curcumin shows beneficial effects on endometriosis pathophysiology, indicating potential therapeutic application.

A systematic review reports that letrozole combined with norethisterone acetate reduces endometriosis-related pain and deep dyspareunia more than norethisterone acetate alone.

A systematic review reported that resveratrol showed beneficial effects suggesting potential application in endometriosis treatment.

In a single RCT, combined oral contraceptives significantly improved mean VAS pain scores for endometriosis-associated pelvic pain (4.54, 95% CI 3.1-5.9; p<0.0001).

A single systematic review found that letrozole does not improve patient satisfaction or influence symptom recurrence after discontinuation in endometriosis-related pain.

A single systematic review reports that letrozole combined with norethisterone acetate causes fewer adverse effects and a lower discontinuation rate than letrozole combined with triptorelin in treating endometriosis-related pain.

A systematic review reported that quercetin showed beneficial effects suggesting potential application in endometriosis treatment.

Relugolix combination therapy is described as having an effect on endometriosis-associated pain versus placebo with reported two-year efficacy in women.

Vilaprisan is a Phase 2 clinical candidate for endometriosis acting as a selective progesterone receptor modulator on the progesterone receptor.

In a randomized trial of women with endometriosis, dienogest (2 mg/day) significantly improved endometriosis-associated pelvic pain (VAS mean difference 6.0, 95% CI 4.9-7.1) and HRQoL, comparable to a combined oral contraceptive.

In a single pilot study, laparoscopic excision plus oral contraceptives significantly reduced chronic pelvic pain intensity in endometriosis patients compared with 6-month follow-up and baseline.

In a single pilot study, oral contraceptives alone significantly reduced chronic pelvic pain and deep dyspareunia in endometriosis patients during and after treatment.

Desogestrel is annotated as a progesterone receptor agonist clinical candidate for endometriosis per Open Targets.

Elagolix sodium is an approved GnRH receptor antagonist indicated for endometriosis per Open Targets annotation.

Open Targets annotates HISTRELIN as an approved-stage GnRH receptor agonist clinical candidate for endometriosis acting on the gonadotropin-releasing hormone receptor.

Relugolix is a GnRH receptor antagonist in Phase 3 clinical development for endometriosis per Open Targets.

A single review-level source asserts that hormonal treatment is vital for managing the painful symptoms of endometriosis, without quantitative data.

A single management article asserts that nonhormonal treatment is vital in managing painful symptoms of endometriosis, without supporting quantitative trial data.

A single patient anecdote describes meloxicam as highly effective ('a miracle drug') for their endometriosis.

Cabergoline is annotated as a Phase 2 clinical candidate for endometriosis acting as a dopamine D2 receptor agonist per Open Targets.

Danazol is an approved small molecule for endometriosis whose annotated mechanism of action is androgen receptor agonism.

ROSIGLITAZONE is a PPAR-gamma agonist listed as a Phase 2 clinical candidate for endometriosis per Open Targets.

Tanezumab, an anti-NGF (beta-nerve growth factor) antibody, is annotated as a Phase 2 clinical candidate for endometriosis.

A single pilot study suggests a treatment for endometriosis-related pain symptoms is promising but warrants further investigation.

Per Open Targets, pentoxifylline is a Phase 3 clinical candidate for endometriosis acting as an adenosine A2b receptor antagonist.

BENTAMAPIMOD is annotated as a Phase 2 clinical candidate for endometriosis acting as a JNK (MAPK8) inhibitor according to Open Targets.

A single patient anecdote claims testosterone 'cured' their endometriosis, with no supporting detail.

Per an Open Targets database annotation, interferon alfa is listed as a Phase 1 clinical candidate for endometriosis.

A single Open Targets database annotation lists LACTULOSE as a clinical candidate for endometriosis at an unknown clinical stage, with no mechanistic or trial detail.

Per Open Targets, vitamin E is a Phase 2 clinical candidate for endometriosis, but no mechanistic pathway evidence is provided.

A systematic review and meta-analysis reported improvement in sexual function with oral desipramine, with or without lidocaine, in women with vestibulodynia.

A state-of-the-science review reports that overnight 5% lidocaine ointment has the highest level of evidence for vulvodynia, supported by at least one RCT or comparative effectiveness trial.

A state-of-the-science review reports multimodal physical therapy has among the highest levels of evidence for vulvodynia, supported by at least one RCT and pre-post reductions in vulvar pain and dyspareunia in non-RCT studies.

A state-of-the-science review notes that botulinum toxin type A 50 units for vulvodynia is supported by at least one RCT or comparative effectiveness trial, giving it the highest level of evidence among reviewed treatments.

A network meta-analysis found oral desipramine with or without lidocaine significantly improved an intercourse symptom score versus other treatments for vestibulodynia in women.

A State-of-the-Science review reports that enoxaparin sodium subcutaneous injections have at least one RCT or comparative effectiveness trial supporting their use for vulvodynia.

In a randomized controlled trial, gabapentin (including extended-release) did not reduce tampon test, intercourse, or daily pain compared with placebo in women with vulvodynia, and the data do not support gabapentin alone as treatment.