Libido — Evidence Map

Libido is a stack-of-systems problem. The literature splits across hormonal substrate (testosterone, estradiol, progesterone, DHEA, prolactin), vascular hardware (PDE5 / cGMP signalling, endothelium, autonomic outflow), central motivation (dopamine, melanocortin, kisspeptin, serotonin balance), neural reflex circuits (the spinal LSt ejaculation generator, supraspinal orgasm circuits), and relational / cognitive context (Basson's responsive desire, the Coolidge effect, partner duration, depression, body image). Any single-mechanism story over-claims. Any drug with a single-mechanism story has to be read against an enormous placebo response in HSDD trials (35–45% on placebo arms).

This evidence map fact-checks an original blog draft against eight research deep dives. Each topic page below is a flowing-prose review with inline source links and per-paragraph confidence tags C1 (primary RCT or guideline) through C5 (folk model with no indexed source). The fact-check page compiles the verdicts on each draft claim into a single colour-tagged map.

Sections

Hormones and Libido: Foundational Evidence

Testosterone, estradiol, progesterone, DHEA and prolactin as libido modulators. Why the "T is the female libido hormone" story is half-right at best, and why estradiol does more within-cycle work than the trade press concedes. Includes the Islam 2019 meta-analysis, Wåhlin-Jacobsen, Roney & Simmons, Cappelletti & Wallen, and the Defreyne ENIGI trans cohort.

hormones-foundations.html

Progestins and Progesterone

Why "progestins lower libido" is true on average and false in detail. Five distinct mechanisms (HPG suppression, AR antagonism, SHBG elevation, ovarian E2 suppression, neurosteroid CNS effects) with effect sizes from Pastor 2013, Boozalis 2016, ECHO 2024, Zethraeus 2017, and the Michael & Zumpe primate study.

progestins-and-progesterone.html

PDE5 Inhibitors

Sildenafil, tadalafil, vardenafil, avanafil — pharmacology, half-lives, contraindications, and the rapidly growing observational mortality literature (Andersson JACC 2021, Kloner 2024, Jehle 2024, Mostafa meta-analysis, Xiao Mendelian-randomization). The "weak evidence" framing in the draft is now under-stated.

pde5-inhibitors.html

Melanocortin: Bremelanotide / PT-141 and Melanotan II

FDA-approved Vyleesi (premenopausal acquired generalized HSDD only — not "libido enhancement"), the RECONNECT trials, the central MC4R mechanism, focal hyperpigmentation as residual MC1R activity, and why Melanotan II is not an acceptable substitute.

melanocortin-pt141.html

Refractory Period and Prolactin

The Krüger 2003 cabergoline single-blind n=10 crossover (often misquoted as "Lancet 2003" double-blind), the 2021 Lima/Valente mouse paper that broke the prolactin-causation story, the LSt spinal ejaculation generator, and what's actually known about modifying refractory time in humans.

refractory-period-prolactin.html

Libido Dampeners

SSRIs and PSSD, antiandrogens (spiro / CPA / bicalutamide / GnRH), 5α-reductase inhibitors and PFS, opioid-induced androgen deficiency, alcohol, cannabis, beta blockers, statins, hyperprolactinemia, depression, hypothyroidism, hypogonadism, sleep deprivation, chronic stress.

libido-dampeners.html

Trans-Specific Libido and Cis-Female T Supplementation

The trans HRT natural experiment as evidence on which hormone does the work. ENIGI longitudinal data: transfem drop in first three months, partial rebound at 36 months; transmasc surge then plateau. Choice of antiandrogen (spiro vs CPA vs bicalutamide vs GnRH) as a libido variable. Cis-female T at upper-female range (Davis 2019 / Parish 2021 ISSWSH guidelines).

trans-specific-libido.html

Missed Topics: Flibanserin, Dopamine, Kisspeptin, Placebo

Flibanserin / Addyi (the actually first FDA-approved HSDD drug, 2015 — four years before bremelanotide), the dopamine system (apomorphine, pramipexole hypersexuality, bupropion, Berridge's wanting-vs-liking), oxytocin / vasopressin (popularity vs evidence), kisspeptin (the credible next-gen candidate), supplements (maca, saffron, ginseng, yohimbine, fenugreek, icariin, tribulus), and the placebo response that swamps every HSDD trial.

missed-topics.html

Verdicts on the original draft

The fact-check page compiles all draft-claim verdicts in one place, organized by the draft's section structure (Sex Hormones, Blood Flow Enhancers, Direct Libido Enhancers, Direct Libido Dampeners, Refractory Period). Each claim gets a colour-tagged verdict: true kind-of-true false understated not-evaluable.

Headline takeaways

"T is the main libido hormone" — kind-of-true for postmenopausal pharmacology (RCT signal there is most robust), false for within-cycle physiology in cycling women (estradiol leads, progesterone suppresses, T is weakly associated). Defreyne ENIGI specifically reports no within-person correlation between absolute serum T and SDI in either trans cohort.
"PT-141 is FDA-approved for libido enhancement" — kind-of-true. Vyleesi is approved for premenopausal women with acquired generalized HSDD, with explicit "Limitations of Use" excluding postmenopausal women, men, and "enhancement of sexual performance." It is also not the first FDA-approved HSDD drug; flibanserin (Addyi, 2015) is.
"Tadalafil is correlated with reduced all-cause mortality, weak evidence" — under-stated. Multi-cohort, multi-country observational data plus an active-comparator design (Andersson 2021) and a Mendelian-randomization analysis (Xiao 2025) all converge on a real signal, with hazard ratios from 0.88 to 0.56. Healthy-user bias remains real but "weak" no longer fits.
"Cabergoline reduced refractory period" — kind-of-true but the mechanism is probably central D2 agonism, not prolactin reduction. Lima 2021 used a peripherally-restricted prolactin-elevator (domperidone) and showed no refractory-period effect, breaking the prolactin-causation hypothesis. The Krüger 2003 study was also single-blind n=10, not double-blind.
"Synthetic progestins lower libido by lowering testosterone" — kind-of-true. Lowering T is the dominant mechanism at high anti-androgen doses (CPA, MPA in forensic dosing). At contraceptive doses there are at least four other mechanisms (SHBG elevation, ovarian E2 suppression, AR antagonism, allopregnanolone CNS effects), and the population-level libido signal is much smaller than community lore implies.