28 compounds were read against these 5 conditions; 13 produced a graded row. The other 15 are named further down.

The ranking, and the key it uses

Ordered by the best rung the compound holds anywhere in this goal; then by what that study measured; then by how many graded rows it holds here, as a tie-break only; then by name. There is no blended score — one number mixing the rung and what was measured would invent a third scale nothing was graded against. Every rung links to the rubric that assigned it.

1. 01

   Cetrorelix

   human RCT · direct outcome · 2 graded rows across 2 of 5 conditions

   Assisted reproduction · Premature LH surge

   2 graded rows, 2 sources

   1. Assisted reproduction

      human RCT Direct outcome Approved for this condition

      Who was studied

      women undergoing controlled ovarian stimulation for IVF or ICSI; Cochrane pooled 73 RCTs, n=12,212, of which 44 trials used cetrorelix; the live birth analysis rests on 12 RCTs, n=2,303

      FDA-approved indication is "inhibition of premature LH surges in women undergoing controlled ovarian stimulation" — a single mechanical step inside an assisted reproduction cycle, not a treatment for infertility. Pooled across RCTs, live birth rate did not differ from the long-course GnRH agonist protocol (OR 1.02, 95% CI 0.85 to 1.23) while ovarian hyperstimulation syndrome was less frequent (OR 0.61, 95% CI 0.51 to 0.72); the drug is what allows the cycle to run to a planned trigger, and no trial tested it as a fertility treatment on its own.

      Source PubMed Central 2 primary sources read for this row

   2. Premature LH surge

      human RCT Direct outcome Approved for this condition

      Who was studied

      women aged 19-40 (mean 32) undergoing controlled ovarian stimulation, n=732 across five trials (two Phase 2, three Phase 3); PCOS, low or absent ovarian reserve, and stage III-IV endometriosis excluded

      FDA-approved indication is "the inhibition of premature LH surges in women undergoing controlled ovarian stimulation" — this condition is the registrational endpoint itself, not an adjunct measure. In the label's clinical trials a premature LH surge (LH >= 10 U/L with progesterone >= 1 ng/mL) occurred in 0 of 115 women on the single 3 mg dose, 1.9% of 159 on 0.25 mg daily in the comparative study, and 1.0% of 303 in the non-comparative study.

      Source DailyMed — the FDA label 1 primary source read for this row

2. 02

   DHEA

   human RCT · direct outcome · 2 graded rows across 2 of 5 conditions

   Low libido · Menopause

   2 graded rows, 2 sources

   1. Low libido

      human RCT Direct outcome Not approved for this condition

      Who was studied

      24 women with adrenal insufficiency, double-blind randomised crossover, oral DHEA 50 mg daily for 4 months and placebo for 4 months with a 1-month washout; this is not a population selected for low sexual desire

      In women with adrenal insufficiency, oral DHEA 50 mg daily increased the frequency of sexual thoughts (P=0.006), sexual interest (P=0.002) and satisfaction with the mental and physical aspects of sexuality (P=0.009 and P=0.02) compared with placebo; the women were enrolled for adrenal insufficiency, not for a diagnosis of low sexual desire, and the instrument was a sexuality questionnaire rather than the FSFI. The separate prescription vaginal insert, prasterone 6.5 mg, is FDA- and EMA-approved for moderate to severe dyspareunia due to menopausal vulvar and vaginal atrophy; dyspareunia is painful intercourse, not low desire, and that approval does not stand for a desire indication and does not transfer to oral over-the-counter DHEA, for which no regulator has approved any product or reviewed any dose. No trial of DHEA in people diagnosed with low sexual desire is on file.

      Source DOI 2 primary sources read for this row

   2. Menopause

      human RCT Direct outcome Approved for this condition

      Who was studied

      postmenopausal women with moderate to severe dyspareunia due to vulvar and vaginal atrophy, in two 12-week placebo-controlled trials of the 6.5 mg prasterone vaginal insert, n=255 and n=558.

      The FDA approved the prasterone 6.5 mg vaginal insert (Intrarosa, NDA 208470) on 17 November 2016 and the European Commission authorised it on 8 January 2018, both for moderate to severe dyspareunia due to menopausal vulvar and vaginal atrophy; the registrational trials measured dyspareunia severity (change -1.27 vs -0.87, p=0.0132; -1.42 vs -1.06, p=0.0002) alongside vaginal superficial cells, parabasal cells and pH. That approval belongs to the vaginal insert and to that single indication, and does not transfer to oral over-the-counter DHEA, for which no regulator has approved any product, established any dose, or reviewed any safety labelling. The strongest randomised evidence on file for oral DHEA is a meta-analysis of 10 placebo-controlled trials in women with adrenal insufficiency reporting a pooled quality-of-life effect size of 0.21, which the authors described as small and possibly trivial; no trial on file measured any menopausal outcome of oral DHEA.

      Source DailyMed — the FDA label 3 primary sources read for this row

3. 03

   Ganirelix

   human RCT · direct outcome · 2 graded rows across 2 of 5 conditions

   Assisted reproduction · Premature LH surge

   2 graded rows, 2 sources

   1. Assisted reproduction

      human RCT Direct outcome Approved for this condition

      Who was studied

      women undergoing controlled ovarian hyperstimulation for IVF or ICSI; Cochrane pooled 73 RCTs, n=12,212, of which 19 trials used ganirelix; registrational open-label study n=463, mean 5.4 days of treatment

      FDA-approved indication is "inhibition of premature LH surges in women undergoing controlled ovarian hyperstimulation" — an adjunct that protects one step of an assisted reproduction cycle rather than a treatment for infertility. The registrational endpoint was the incidence of a premature LH surge (under 1% of 463 subjects), which is a process measure, not a pregnancy; the live birth comparison against the long agonist protocol comes from the Cochrane pooled analysis (OR 1.02, 95% CI 0.85 to 1.23) and shows no difference.

      Source PubMed Central 2 primary sources read for this row

   2. Premature LH surge

      human RCT Direct outcome Approved for this condition

      Who was studied

      women undergoing controlled ovarian hyperstimulation, multicentre open-label randomised study, n=463 on ganirelix 250 mcg subcutaneously daily from day 6 of recombinant FSH, with a luteal-phase GnRH agonist as reference

      FDA-approved indication is "the inhibition of premature LH surges in women undergoing controlled ovarian hyperstimulation" — on this condition the registrational endpoint is the outcome itself: a premature LH surge before hCG (LH rise >= 10 mIU/mL with progesterone > 2 ng/mL or a significant oestradiol decline) occurred in under 1% of the 463 subjects. The same trial graded as a process measure on the assisted-reproduction page is direct evidence here.

      Source DailyMed — the FDA label 1 primary source read for this row

4. 04

   PT-141

   human RCT · direct outcome · 2 graded rows across 2 of 5 conditions

   Low libido · Menopause

   2 graded rows, 2 sources

   1. Low libido

      human RCT Direct outcome Approved for this condition

      Who was studied

      premenopausal women with acquired, generalised hypoactive sexual desire disorder, n=1247 randomised across two identical 24-week Phase III trials (RECONNECT, NCT02333071 and NCT02338960), mean age 39; postmenopausal women and men were outside the enrolled population

      The FDA approved bremelanotide (Vyleesi, 1.75 mg subcutaneous, initial US approval 2019) for premenopausal women with acquired, generalised hypoactive sexual desire disorder, and the label states plainly that it is not indicated for hypoactive sexual desire disorder in postmenopausal women or in men, and not to enhance sexual performance. The registrational trials measured the Female Sexual Function Index desire domain (integrated effect 0.35, P<.001) and the Female Sexual Distress Scale desire/arousal/orgasm item 13 (integrated effect -0.33, P<.001) against placebo, both validated desire endpoints. Nausea, flushing and headache each occurred in at least 10% of women given bremelanotide; no trial in postmenopausal women or in men is on file, so nothing here establishes what the compound does in those populations.

      Source DOI 2 primary sources read for this row

   2. Menopause

      human RCT Direct outcome Not approved for this condition

      Who was studied

      premenopausal women only, in two identical Phase III randomised double-blind placebo-controlled trials (NCT02333071, NCT02338960) and a Phase II dose-finding trial (NCT01382719); postmenopausal women were outside the enrolled population in every one of them.

      Bremelanotide is FDA-approved (Vyleesi, NDA 210557, 21 June 2019) for acquired, generalised hypoactive sexual desire disorder in PREMENOPAUSAL women, and the registrational trials measured desire and distress scores in that population. That approval sits in an adjacent population and is not an approval for postmenopausal hypoactive sexual desire disorder or for any other menopausal indication. No trial in postmenopausal women is on file, so nothing here establishes what the compound does after the menopause.

      Source ClinicalTrials.gov 3 primary sources read for this row

5. 05

   Testosterone

   human RCT · direct outcome · 2 graded rows across 2 of 5 conditions

   Low libido · Menopause

   2 graded rows, 2 sources

   1. Low libido

      human RCT Direct outcome Off-label use

      Who was studied

      two separate populations. Women: postmenopausal women with hypoactive sexual desire disorder, pooled from blinded randomised placebo-controlled trials of at least 12 weeks (Islam 2019 meta-analysis), at roughly one tenth of the male replacement dose; premenopausal women were not the studied population. Men: 470 men aged 65 or over with low libido and average total testosterone below 275 ng/dL, randomised to testosterone gel or placebo for 1 year (the Testosterone Trials sexual function trial).

      In postmenopausal women, randomised trials measured satisfying sexual events and desire, arousal and orgasm domains, and the 2019 Global Consensus Position Statement records postmenopausal hypoactive sexual desire disorder as the only indication the randomised evidence supports; no testosterone product is approved for women anywhere, so male formulations are used off-label at about a tenth of the male dose, with acne and hirsutism the reported excess adverse effects, and no randomised safety data beyond about two years. In older men with low testosterone, a separate question and a separate trial population, the Testosterone Trials sexual function trial measured the Psychosexual Daily Questionnaire and reported significantly greater sexual activity, sexual desire and erectile function than placebo over one year; that evidence is about hypogonadism in men and does not transfer to women, and the female evidence does not transfer to men. Approved male testosterone products are labelled for hypogonadism, not for low sexual desire as such.

      Source DOI 3 primary sources read for this row

   2. Menopause

      human RCT Direct outcome Off-label use

      Who was studied

      postmenopausal women diagnosed with hypoactive sexual desire disorder after biopsychosocial assessment, pooled from blinded randomised placebo-controlled trials of at least 12 weeks (Islam 2019); no randomised data beyond about two years, and no breast cancer or cardiovascular endpoint data in women, are on file.

      In postmenopausal women with hypoactive sexual desire disorder, randomised trials measured satisfying sexual events and reported an average increase of about one per month, with changes in desire, arousal, orgasm, pleasure and sexual responsiveness. The same body of randomised evidence measured cognition, bone mineral density at spine, hip and femoral neck at 12 months, depressed mood and general wellbeing, and lean mass, total fat and muscle strength, and demonstrated no effect on any of them in women; the 2019 Global Consensus Position Statement records the evidence for those outcomes as insufficient. No testosterone product is FDA-approved for women, so use in this population is off-label in male formulations at roughly one tenth the male replacement dose, and reported excess adverse effects were acne and hirsutism.

      Source DOI 3 primary sources read for this row

6. 06

   Estradiol

   human RCT · direct outcome · 1 graded row across 1 of 5 conditions

   Menopause

   1 graded row, 1 source

   1. Menopause

      human RCT Direct outcome Approved for this condition

      Who was studied

      postmenopausal and otherwise hypoestrogenic women; the FDA labelling states no n or trial duration for the vasomotor efficacy data. The one randomised trial read in full, ELITE, enrolled 643 healthy postmenopausal women on oral 1 mg/day for a median of about 5 years, stratified by time since menopause.

      The FDA has approved estradiol for moderate to severe vasomotor symptoms of the menopause, for moderate to severe vulvar and vaginal atrophy, and for prevention of postmenopausal osteoporosis; the first two are patient-reported menopausal symptoms and the third is a bone-density indication. ELITE separately measured carotid intima-media thickness, which progressed more slowly than placebo only in women randomised within 6 years of menopause, and measured coronary atherosclerosis by CT, which did not differ significantly from placebo in either stratum. The labelling carries a boxed warning covering endometrial cancer, cardiovascular disorders, probable dementia and breast cancer, and states that oestrogens should not be used for the prevention of cardiovascular disease.

      Source DailyMed — the FDA label 3 primary sources read for this row

7. 07

   Leuprolide

   human RCT · direct outcome · 1 graded row across 1 of 5 conditions

   Assisted reproduction

   1 graded row, 1 source

   1. Assisted reproduction

      human RCT Direct outcome Off-label use

      Who was studied

      women in GnRH-antagonist IVF/ICSI cycles; Cochrane review 17 RCTs, n=1,847, of which the fresh autologous live birth analysis covers 5 RCTs, n=532

      Leuprolide's approved indications are advanced prostate cancer, endometriosis, uterine fibroids and central precocious puberty; use for pituitary downregulation or as an alternative trigger inside an assisted reproduction cycle is off-label, and is a step in a cycle rather than a treatment for infertility. Used as the trigger in fresh autologous cycles it was associated with a lower live birth rate than hCG (OR 0.47, 95% CI 0.31 to 0.70), with less ovarian hyperstimulation syndrome.

      Source PubMed 2 primary sources read for this row

8. 08

   Melanotan II

   human RCT · direct outcome · 1 graded row across 1 of 5 conditions

   Low libido

   1 graded row, 1 source

   1. Low libido

      human RCT Direct outcome Not approved for this condition

      Who was studied

      20 men with psychogenic and organic erectile dysfunction, double-blind placebo-controlled crossover, subcutaneous dosing; an earlier crossover in the same programme enrolled 10 men with erectile dysfunction of no known organic cause

      Melanotan II is an unapproved non-selective alpha-MSH analogue; no regulator has approved it for low sexual desire, erectile dysfunction, or anything else, in any country. In a double-blind placebo-controlled crossover in 20 men, Melanotan II produced penile erection in 17 of 20 in the absence of sexual stimulation with a mean 41 minutes of RigiScan tip rigidity above 80%, and increased sexual desire was reported after 13 of 19 Melanotan II doses versus 4 of 21 placebo doses (P<0.01); that desire measure was an investigator-collected report, not a validated instrument such as the IIEF. Nausea and yawning were frequent, with severe nausea in 12.9% of subjects at 0.025 mg/kg, and no trial in women and no trial of a desire endpoint as a primary outcome is on file.

      Source PubMed 2 primary sources read for this row

9. 09

   Oxytocin

   human RCT · direct outcome · 1 graded row across 1 of 5 conditions

   Low libido

   1 graded row, 1 source

   1. Low libido

      human RCT Direct outcome Not approved for this condition

      Who was studied

      30 pre- and postmenopausal women with sexual dysfunction, randomised double-blind placebo-controlled crossover over 22 weeks, intranasal oxytocin 32 IU self-administered within 50 minutes before intercourse for 8-week periods

      This is the one trial on file that measured a validated desire endpoint in women with sexual dysfunction rather than physiology in healthy volunteers, and it was negative: the Female Sexual Function Index rose 26% on oxytocin and 31% on placebo, the Sexual Interest and Desire Inventory 29% and 23%, and the Sexual Quality of Life 144% and 125%, with no statistically significant difference between oxytocin and placebo on any measure. The authors concluded that oxytocin and placebo improved sexual function comparably. Oxytocin is not approved for low sexual desire by any regulator; the remaining human oxytocin literature relevant here is single-dose physiology and brain-imaging work in healthy volunteers, which measured no desire outcome in an affected population.

      Source DOI 1 primary source read for this row

10. 10

    Progesterone

    human RCT · direct outcome · 1 graded row across 1 of 5 conditions

    Menopause

    1 graded row, 1 source

    1. Menopause

       human RCT Direct outcome Approved for this condition

       Who was studied

       non-hysterectomised postmenopausal women receiving conjugated oestrogens, for the labelled endometrial-hyperplasia indication. The randomised vasomotor trial enrolled a different population: perimenopausal women, n=189, 4 months, 300 mg oral micronised progesterone at bedtime.

       The FDA-approved menopausal indication is prevention of endometrial hyperplasia in non-hysterectomised postmenopausal women taking conjugated oestrogens, and the endpoint there is endometrial histology, not a menopausal symptom. For vasomotor symptoms the 2023 Phase III Canada-wide randomised placebo-controlled trial (Sci Rep, PMC10241804) missed its primary endpoint: rate ratio 0.79, 95% CI 0.54-1.15, p=0.222, with secondary measures of perceived night sweats and sleep favouring progesterone. That trial enrolled perimenopausal women; the other randomised vasomotor trial in postmenopausal women (Hitchcock and Prior, Menopause 2012) was paywalled and was not read, so no postmenopausal vasomotor result is on file here.

       Source DailyMed — the FDA label 3 primary sources read for this row

11. 11

    hCG

    human RCT · surrogate marker · 2 graded rows across 2 of 5 conditions

    Assisted reproduction · Low libido

    2 graded rows, 2 sources

    1. Assisted reproduction

       human RCT Surrogate marker Approved for this condition

       Who was studied

       infertile women pretreated with FSH after pituitary desensitisation in an IVF and embryo transfer programme; pivotal randomised study n=94 receiving choriogonadotropin alfa 250 mcg

       FDA-approved (Ovidrel) for "the induction of final follicular maturation and early luteinization" in women already in an ART programme — that is the trigger step of a cycle, not a treatment for infertility. The pivotal trial's primary endpoint was the number of oocytes retrieved (mean 13.6), a surrogate; clinical pregnancy per initiated cycle (35.1%) was secondary and the trial was designed to show equivalence to urinary hCG, not to measure live birth.

       Source DailyMed — the FDA label 1 primary source read for this row

    2. Low libido

       human case series Direct outcome Off-label use

       Who was studied

       20 men with hypogonadal symptoms and total testosterone above 300 ng/dL, multi-institutional retrospective review, median 8 months of hCG monotherapy, no control group

       In a retrospective series of 20 men treated for low libido, fatigue or erectile dysfunction, mean total testosterone rose 49.9% from 362 to 519.8 ng/dL and 50% of patients reported symptom improvement; the symptom report was uncontrolled and used no validated desire instrument such as the IIEF, so the testosterone figure is the only quantified result and it is a surrogate marker. Reports of improved libido in men treated with hCG for hypogonadotropic hypogonadism come from similarly uncontrolled series. hCG is approved for other indications, including hypogonadotropic hypogonadism in males, and is not approved for low sexual desire by any regulator; no randomised trial with a desire endpoint is on file.

       Source DOI 1 primary source read for this row

12. 12

    Gonadorelin

    human observational · direct outcome · 2 graded rows across 2 of 5 conditions

    Assisted reproduction · Pituitary gonadotroph testing

    2 graded rows, 2 sources

    1. Assisted reproduction

       human observational Direct outcome Not approved for this condition

       Who was studied

       women aged 20–40 with functional hypothalamic amenorrhoea, n=66, 82 treatments and 212 ovulation induction cycles, 1996–2020; subcutaneous pulsatile gonadorelin 10 mcg every 90 minutes by pump

       This is pulsatile ovulation induction outside assisted reproduction, not an adjunct within an IVF cycle: a retrospective single-centre cohort reported a cumulative live birth rate of 65.9% per treatment and 96% ovulation per cycle in functional hypothalamic amenorrhoea. No gonadorelin product currently marketed in the US carries an approval for use in assisted reproduction, and the cohort is uncontrolled, so the rate cannot be read as an effect size.

       Source PubMed Central 1 primary source read for this row

    2. Pituitary gonadotroph testing

       human observational Direct outcome Not approved for this condition

       Who was studied

       girls with early pubertal signs, n=263 (314 diagnostic tests) plus 270 monitoring tests during leuprolide treatment, mean age 7.9 years; intravenous gonadorelin acetate with LH and FSH sampled to 90 minutes

       This is a diagnostic-agent use, not a treatment: a single intravenous dose of gonadorelin stimulates the pituitary gonadotrophs and the LH response is read as the result. In this cohort a 40-minute LH sample at a 5 IU/L cut-off identified central precocious puberty with 98% sensitivity and 100% specificity against the full sampled test. The former US human product (Factrel) carried exactly this diagnostic indication — evaluating the functional capacity of the anterior pituitary gonadotropes — but was withdrawn, and no human gonadorelin product is currently FDA-approved; the Factrel name on DailyMed today is a veterinary product.

       Source PubMed Central 1 primary source read for this row

13. 13

    GHRP-6

    in vitro · surrogate marker · 1 graded row across 1 of 5 conditions

    Assisted reproduction

    1 graded row, 1 source

    1. Assisted reproduction

       in vitro Surrogate marker Not approved for this condition

       Who was studied

       240 human germinal vesicle oocytes cultured in vitro across varying GHRP-6 concentrations, with blastocyst medium as control and 10 per cent human tubal fluid as sham; a further 164 oocytes used for gene expression

       GHRP-6 was added to in vitro maturation culture medium rather than given to a patient. At 75 ng/mL the maturation rate was 70 per cent on day one and 80 per cent on day two, above the other media tested. The paper is explicit about the limit: expression of CENP-E and LINGO2 did not rise, and no statistically significant improvement in cytoplasmic maturation at metaphase II was shown. Maturation rate in a dish is several steps from a pregnancy or a live birth, and no fertilisation, implantation or birth outcome was measured. Rung set from the study's own design wording, "cultured".

       Source PubMed 1 primary source read for this row

Checked, and nothing on file

15 compounds were read against these conditions and produced no gradeable row. They are named here rather than left off, because a list of 13 reads identically whether 13 survived 28 or 13 were all anyone thought of.

1. C-Max

   No rung — nothing on file to grade

   Checked against low libido. No study meeting the rubric was found for any of them.

2. Collagen Peptides

   No rung — nothing on file to grade

   Checked against menopause. No study meeting the rubric was found for any of them.

3. CRH (Corticotropin-Releasing Hormone) on pituitary gonadotroph testing

   No rung — nothing on file to grade Not approved for this condition

   Wrong cell type. CRH stimulates corticotrophs and is read out as ACTH and cortisol; the gonadotroph test uses GnRH or gonadorelin and is read out as LH and FSH. CRH has no place in gonadotroph testing and earns no row here. The corpus has no corticotroph equivalent of this condition, which is where CRH's only licensed use would sit: corticorelin ovine triflutate is approved in the United States for distinguishing pituitary from ectopic ACTH production in ACTH-dependent Cushing's syndrome, and a Cleveland Clinic series of 65 patients with Cushing's disease and 42 in whom it was excluded found the dexamethasone-CRH test detected 5 cases (7.7%) that low-dose dexamethasone alone missed, at 100% sensitivity and 93% specificity (https://pubmed.ncbi.nlm.nih.gov/36917416/). That is a diagnostic-accuracy finding with no treatment outcome, and it has nowhere to go until the condition exists.

4. Epitalon

   No rung — nothing on file to grade

   Checked against menopause. No study meeting the rubric was found for any of them.

5. GHK-Cu

   No rung — nothing on file to grade

   Checked against menopause. No study meeting the rubric was found for any of them.

6. GHRH (Growth Hormone-Releasing Hormone) on pituitary gonadotroph testing

   No rung — nothing on file to grade Not approved for this condition

   GHRH is a diagnostic stimulus for the somatotroph, not the gonadotroph. Gonadotroph testing uses gonadorelin, so the condition does not apply to this compound even though GHRH has a long diagnostic record of its own.

7. GnRH (Gonadotropin-Releasing Hormone)

   No rung — nothing on file to grade

   Checked against assisted reproduction, pituitary gonadotroph testing. No study meeting the rubric was found for any of them.

8. Kisspeptin-10

   No rung — nothing on file to grade

   Checked against low libido, assisted reproduction, menopause. No study meeting the rubric was found for any of them.

9. Melanotan I on low libido

   No rung — nothing on file to grade Not approved for this condition

   Melanotan-I is the MC1R-selective analogue and does not carry the MC4R erectile and libido literature; that belongs to melanotan-II and bremelanotide. No trial of melanotan-I has measured a sexual-function outcome.

10. MOTS-c

    No rung — nothing on file to grade

    Checked against menopause. No study meeting the rubric was found for any of them.

11. Selank

    No rung — nothing on file to grade

    Checked against menopause. No study meeting the rubric was found for any of them.

12. Semax

    No rung — nothing on file to grade

    Checked against menopause. No study meeting the rubric was found for any of them.

13. Simonson Alpha 1

    No rung — nothing on file to grade

    Checked against low libido. No study meeting the rubric was found for any of them.

14. SS-31

    No rung — nothing on file to grade

    Checked against menopause. No study meeting the rubric was found for any of them.

15. Thymosin alpha-1

    No rung — nothing on file to grade

    Checked against menopause. No study meeting the rubric was found for any of them.

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