# Check — Puberty and Early Sexual Development (Foundations, lecture 3 of 4)

Checked 2026-10-19. 54 claims checked; 14 corrected; 2 removed.

Length 2077 → 1944 words (−6.4%), per the task's instruction to bring the script to 1950 or fewer; cuts were connective phrasing only, every slide, figure, name, drug and date retained. Markup intact after edits: 16 `##` slides (one per beat, deck slides 1+2 merged into the opening slide and deck slide 5 split into the pulse and adrenarche slides, as the writer had it), one `? ` paragraph, no `> ` quotations (the deck has none), no lists, no parentheses or slashes, no `###`, no `[+]`/`[fixed]` markers left, lecturer not named anywhere in the narration (she is "the course director" and "the lecturer"). The writer's one `[fixed]` (Camcevi is leuprolide mesylate, not acetate) is confirmed.

## Corrections (script changed)
- Slide 1 (opening): "a physician who directs the Northwest Institute on Intimacy" → "the course director at the Northwest Institute on Intimacy". Deck slide 2 says "course director at", not that she directs the institute. The teaching-emphasis sentence ("developmental patterns, evolutionary theory and inclusive care") was dropped for length; lecture 2's opening already carries it.
- Slide 3 (From birth until puberty): mini-puberty "settle back over roughly the first six months" → "over roughly the first six months in boys, more slowly in girls". In boys LH, FSH and testosterone return to prepubertal values by about 6 (gonadotropins 6–9) months; in girls LH falls on the same schedule but FSH stays elevated for up to 3–4 years. Sources: https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2020.00187/pdf ; https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2020.612235/pdf
- Slide 3: boys' spurt "reaches a higher peak" → "a somewhat higher peak". Longitudinal series do put boys' peak height velocity above girls' (commonly cited ~10 cm/yr at 14 vs ~9 cm/yr at 12; Belgian cohort 9.1 vs 7.5; Colombian 7.4 vs 7.0), but the gap is modest and some cross-sectional series reverse it. Sources: https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.718292/full ; https://pmc.ncbi.nlm.nih.gov/articles/PMC4677560
- Slide 5 (Adrenarche): "accounts for the first body odour, the first pubic and underarm hair, and often the first acne" → "underlies the first adult body odour and often the first pubic and underarm hair and the first acne". Adrenarche's clinical features are pubic hair, axillary hair, body odour and acne, but in ordinary puberty gonadal androgens also drive pubarche, so "accounts for" overstated it. Sources: https://www.speg.scot.nhs.uk/wp-content/uploads/sites/36/2022/07/3.-2022-SPEG-Adrenarche-Guideline.pdf ; https://pmc.ncbi.nlm.nih.gov/articles/PMC7891873
- Slide 6 (What sets puberty off): deck's "Since the 20th century, puberty has been noted to begin much earlier" → "Over the past century and a half". The recorded decline runs from the mid-1800s (Oslo 15.6 years in 1861 → 13.3 in 1940; the Norwegian trend had halted by 1970). Sources: https://tidsskriftet.no/en/2020/09/kronikk/puberty-starting-earlier ; https://www.nature.com/articles/241478a0
- Slide 6: "near 17 in the mid-1800s" → "roughly 15 to 17 in the mid-1800s and near 13 a century later". The 17-year figure is Tanner's classic Norwegian point (Foetus into Man, 1978, maternity-clinic recall data); re-analysis of Oslo records gives 15.6 in 1861, and general 19th-century European estimates run 16–18. The range covers both; the endpoint near 13 by the 1960s is undisputed (Oslo schoolgirls 13.27 in 1952, 13.24 in 1970). Sources: https://worldhistorycommons.org/age-menarche-norway ; https://tidsskriftet.no/en/2020/09/kronikk/puberty-starting-earlier ; https://www.nature.com/articles/241478a0 ; https://en.wikipedia.org/wiki/Menarche
- Slide 8 (Expected ages): the deck's FAB precocious-puberty list includes "breast and endometrial cancers" and "greater all cause mortality" under what the script attributes to the UK Biobank. Day et al. 2015 (UK Biobank, 250,037 women / 197,714 men) reports breast cancer but **not** endometrial cancer, and did **not** assess mortality. Both associations are real but come from other work (endometrial cancer: dose-response meta-analysis of 8 prospective studies, RR 0.96 per 2-year delay, oldest-vs-youngest RR 0.68; all-cause mortality: meta-analysis of 9 cohorts, HR 0.97 per year later, 1.23 for menarche <12). Script now reads "…poor sleep quality and short stature, and in other cohorts with endometrial cancer and greater all-cause mortality." Sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC4471670/ ; https://pmc.ncbi.nlm.nih.gov/articles/PMC4566123/ ; https://pmc.ncbi.nlm.nih.gov/articles/PMC4070937/
- Slide 8: "lower scores on measures of intelligence" (deck: "low intelligence") → "a low score on a test of fluid intelligence". The UK Biobank outcome is the binary category "Low intelligence (Fluid)", a score of 2 or less out of 13 on its fluid-intelligence test (~3.8% of the sample). Source: https://pmc.ncbi.nlm.nih.gov/articles/PMC4471670/
- Slide 10 (The Ashley case): "the ethics committee at Seattle Children's" → "the ethics committee at the Seattle children's hospital" (in 2004 the institution was Children's Hospital and Regional Medical Center; the ethics consultation was 5 May 2004). "a Washington disability-rights review found…" → "the state's disability protection and advocacy agency found … a finding the hospital accepted" (Washington Protection and Advocacy System investigative report, 8 May 2007: no court order sought or obtained; violation of Washington law; Children's Hospital agreed to corrective action). Sources: https://archive.crin.org/en/docs/drw_ashley_treatment.pdf ; https://en.wikipedia.org/wiki/Ashley_Treatment ; https://bioethics.com/?p=2392
- Slide 11 (GnRH analogues): leuprolide "is used for prostate cancer, endometriosis, uterine fibroids and central precocious puberty" → "across those products is used for…". Camcevi (mesylate) and Eligard are approved only for advanced prostate cancer; Fensolvi only for CPP; Lupron Depot carries the adult indications and Lupron Depot-PED the CPP one. Sources: https://www.urologytimes.com/view/fda-approves-new-subcutaneous-formulation-of-leuprolide-mesylate-for-prostate-cancer ; https://professionals.OptumRx.com/content/dam/optum3/professional-optumrx/news/rxnews/drug-approvals/drugapproval_camcevi_2021-0602.pdf ; https://www.fepblue.org/-/media/PDFs/Medical-Policies/2026/July-2026/Pharmacy-Policies/Remove--Replace/5_30_067-Leuprolide.pdf ; https://www.healio.com/clinical-guidance/drugs/fensolvi
- Slide 11: "the same drug was sold as Vantas for prostate cancer" → "…until 2021". Endo discontinued the Vantas 50 mg histrelin implant on 21 September 2021 (manufacturing problem with no corrective action identified); Supprelin LA remains on the market. The deck lists "Vantas Histrelin Implant" as if current. Sources: https://kffhealthnews.org/republish/news/hormone-blocker-sticker-shock-again-as-patients-lose-cheaper-drug-option/ ; https://go.drugbank.com/salts/DBSALT001172
- Slide 12 (Sexual dimorphism): deck definition "look different based on which sex chromosome they carry" → "looking different according to their sex, which in mammals follows the sex chromosomes they carry". Sexual dimorphism is defined by sex, not by chromosomes (birds, many reptiles and fish have ZW, temperature-dependent or other systems). Source: https://en.wikipedia.org/wiki/Sexual_dimorphism
- Slide 12: mandrill "roughly 3 times the female's body mass" → "roughly 2 to 3 times" (Setchell's asymptotic 31.2 vs 9.1 kg = 3.4×; Wikipedia's ranges 19–30 vs 10–15 kg ≈ 2×); "coloration that she lacks" → "far more muted in her" (females have subdued facial colouring); "the colours deepen with his testosterone and his rank" → "the red deepens…" (Setchell & Dixson: red, not blue, tracks testosterone and rank; losing alpha status reduces red but not blue). Sources: https://durham-repository.worktribe.com/output/1543130 ; https://pmc.ncbi.nlm.nih.gov/articles/PMC1636084 ; https://en.wikipedia.org/wiki/Mandrill
- Slide 15 (Childhood sexual behaviour): four changes against the HealthyChildren.org page itself. (a) "by age band" → "children aged two through six" (the table is "Examples of Sexual Behaviors in Children Aged 2 Through 6 Years"; there is no second age band). (b) third column label → "uncommon but seen in normal children" (page: "Uncommon behaviors in normal children"). (c) the first-column examples: "asking where babies come from" is not in the table and was removed; now "Touching one's own genitals and curiosity about other people's bodies" (page: touching own genitals; viewing a peer's or new sibling's genitals; trying to view peers or adults nude). (d) the red-flag sentence: "not its content but its features: coercion, a large gap in age or development…, knowledge of adult sexual acts beyond the child's stage, and persistence after calm redirection" → "mostly its features: coercion or force, an age gap of four or more years between the children, behaviour that causes distress or pain or comes with aggression, behaviour that is daily and cannot be redirected, and imitation of adult sexual acts". The page's "rarely normal" column and its red-flag list use exactly these criteria (4+ years apart; daily; distress or pain; aggression; coercion; persistent and angry if distracted; "simulates penetrative and/or adult sexual acts"); it does not use "knowledge beyond age", and one criterion is content, so "not its content" was wrong. Source: https://www.healthychildren.org/English/ages-stages/preschool/Pages/Sexual-Behaviors-Young-Children.aspx

## Verified (unchanged)
- Slide 11: Camcevi is leuprolide **mesylate** (42 mg six-monthly subcutaneous emulsion, FDA approval May 2021, Foresee/Accord; a 3-month 21 mg form approved August 2025); the deck listed it under leuprolide acetate. Writer's `[fixed]` confirmed. Sources: https://www.urologytimes.com/view/fda-approves-new-subcutaneous-formulation-of-leuprolide-mesylate-for-prostate-cancer ; https://professionals.OptumRx.com/content/dam/optum3/professional-optumrx/news/rxnews/drug-approvals/drugapproval_camcevi_2021-0602.pdf
- Slide 3: growth velocity highest in infancy (~25 cm/yr falling to ~10 cm/yr by the end of year one), relatively constant through childhood (4–7 cm/yr, lowest just before puberty), childhood growth controlled mainly by the GH–IGF-1 axis with thyroid hormone; IGF-1 produced by the liver in response to GH. Sources: https://www.ncbi.nlm.nih.gov/books/NBK278971/ ; https://www.endotext.org/wp-content/uploads/word/disorders-of-growth-hormone-in-childhood.pdf
- Slide 3: girls' spurt early in puberty, boys' about 2 years later — age at peak height velocity 12.2 vs 13.4 (Brazil), 10.4 vs 12.7 (Colombia), 11.6 vs 14.0 (Belgium). Sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC6950178 ; https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.718292/full ; https://pmc.ncbi.nlm.nih.gov/articles/PMC4677560
- Slide 4: continuous GnRH desensitises the pituitary and shuts down gonadotropin release, while hourly pulses restore it — Belchetz, Plant, Nakai, Keogh & Knobil, Science 1978;202:631. Source: https://pubmed.ncbi.nlm.nih.gov/100883/
- Slide 11: GnRH agonists first stimulate (flare) then desensitise pituitary GnRH receptors, suppressing LH/FSH and gonadal steroids for as long as the drug is present; reversible. Sources: Camcevi mechanism summary above; https://pubmed.ncbi.nlm.nih.gov/100883/
- Slide 4: reference intervals for LH, FSH, estradiol and testosterone are published by age, sex and Tanner stage (CALIPER; Koskas 2007; Soldin 2005) and prepubertal values are at the low end. Sources: https://www.degruyterbrill.com/document/doi/10.1515/CCLM.2007.086/html ; https://www.aruplab.com/files/resources/pediatrics/References-pediatric-reference-intervals.pdf ; https://pmc.ncbi.nlm.nih.gov/articles/PMC3636986
- Slide 5: adrenarche = maturation of the zona reticularis (innermost adrenal cortex); DHEA and DHEA-S the principal products; onset 6–8 years, about two years before gonadal puberty; independent of GnRH-driven gonadal activation. Sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC7891873 ; https://www.speg.scot.nhs.uk/wp-content/uploads/sites/36/2022/07/3.-2022-SPEG-Adrenarche-Guideline.pdf ; https://my.clevelandclinic.org/health/body/adrenarche
- Slide 5: "blocking GnRH does not stop it" — during GnRH-agonist suppression for CPP, DHEA-S stays flat or rises age-appropriately; adrenarche progresses normally. Sources: https://pubmed.ncbi.nlm.nih.gov/2937629 (Wierman et al., JCI 1986) ; https://iris.unipv.it/handle/11571/579250
- Slide 6: "complete slightly later" — kept as the course's observation; supported for girls by the Copenhagen Puberty Study (earlier thelarche with prolonged pubertal duration, 1991–93 vs 2006–08). Source: https://www.qxmd.com/r/19403485
- Slide 6: 50–80% of variation in pubertal timing genetic — heritability of age at menarche 50–80% across twin/family designs; ≥70% in ~5,000 Dutch twins and relatives. Sources: https://link.springer.com/doi/10.1007/s10519-007-9161-4 ; https://pmc.ncbi.nlm.nih.gov/articles/PMC2964498
- Slide 7: "hundreds of genes" (deck: 400 and counting) — 389 independent signals for age at menarche in ~370,000 women (Day et al., Nat Genet 2017), up from 123 signals in 2014. Sources: https://doi.org/10.1038/ng.3841 ; https://www.doi.org/10.1038/nature13545
- Slide 7: kisspeptin/KISS1R as "gatekeeper" of GnRH neurons — inactivating GPR54/KISS1R mutations cause hypogonadotropic hypogonadism (two groups, 2003); kisspeptin acts directly on GnRH neurons. Sources: https://pubmed.ncbi.nlm.nih.gov/16915001 ; https://pmc.ncbi.nlm.nih.gov/articles/PMC2858313
- Slide 8: expected onset 8–13 (FAB) and 9–14 (MAB); precocious before 8/9 — matches standard definitions. Source: https://medicinetoday.com.au/system/files/pdf/medicine_today/article/MT2007-05-026-CAMPBELL.pdf
- Slide 8: the deck's MAB precocious list (short stature, T2D, cardiovascular disease, IBS, depression, poor overall health, poor sleep), FAB delayed list (early natural menopause, malabsorption/coeliac disease, low fluid intelligence, asthma, poor overall health, poor sleep) and MAB delayed list (anxiety/panic attacks, depression, asthma, eczema/dermatitis) match Day et al. 2015's adjusted results item for item; the FAB precocious items T2D, angina/hypertension (the paper's cardiovascular outcomes), breast cancer, uterine fibroids, hiatus hernia, osteoarthritis, poor sleep and short stature also match. All outcomes self-reported. Source: https://pmc.ncbi.nlm.nih.gov/articles/PMC4471670/
- Slide 10: Ashley X born 1997, static encephalopathy, "pillow angel" because she stays where placed; parents sought growth attenuation in 2004 when she was six; ethics committee (40 members, chaired by Diekema) consulted May 2004; treatment = high-dose estrogen to advance epiphyseal closure, hysterectomy (ovaries retained), breast-bud removal (plus appendectomy, not in the script); published Gunther & Diekema, Arch Pediatr Adolesc Med, October 2006, 160(10). Sources: https://en.wikipedia.org/wiki/Ashley_Treatment ; https://archive.crin.org/en/docs/drw_ashley_treatment.pdf
- Slide 10: WPAS report dated 8 May 2007; Ashley six at the time; no court order sought or obtained; Washington Supreme Court requires one before sterilising a person with a developmental disability; hospital agreed to corrective action and now requires court orders for growth-attenuation procedures. Description in the script is neutral (facts, then the course's questions; no verdict). Source: https://archive.crin.org/en/docs/drw_ashley_treatment.pdf
- Slide 9: PillowAngel.org is the parents' site (the WPAS report cites pillowangel.org documents of January 2007). Source: https://archive.crin.org/en/docs/drw_ashley_treatment.pdf
- Slide 11: Lupron Depot — advanced prostate cancer, endometriosis, fibroid-related anaemia (with iron); Lupron Depot-PED — CPP; Eligard — advanced prostate cancer; Fensolvi — CPP in children 2 and older. Sources: https://www.fepblue.org/-/media/PDFs/Medical-Policies/2026/July-2026/Pharmacy-Policies/Remove--Replace/5_30_067-Leuprolide.pdf ; https://www.healio.com/clinical-guidance/drugs/fensolvi
- Slide 11: Zoladex (goserelin acetate) — prostate cancer, advanced breast cancer, endometriosis (also endometrial thinning). Sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC11326481/table/cancers-16-01032-t004 ; https://www.drugbank.ca/categories/DBCAT004268
- Slide 11: Trelstar (triptorelin pamoate) — advanced prostate cancer; Triptodur — CPP in children 2 and older, FDA approved 29 June 2017, 22.5 mg IM six-monthly. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208956Orig1s000Approv.pdf ; https://www.drugbank.ca/categories/DBCAT004268
- Slide 11: Supprelin LA (histrelin acetate) — 50 mg subcutaneous implant in the inner aspect of the upper arm, 12 months, CPP in children 2 and older. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022058s006lbl.pdf ; https://www.drugs.com/pro/supprelin-la.html
- Slide 11: Vantas — the 50 mg histrelin implant for advanced prostate cancer. Source: https://go.drugbank.com/salts/DBSALT001172
- Slide 11: Synarel (nafarelin acetate) nasal solution — endometriosis and CPP. Source: https://www.pahealthwellness.com/content/dam/centene/Pennsylvania/policies/pharmacy-policies/19.09.10_REVIEW_PA.CP.PHAR.174%20Nafarelin%20Acetate%20(Synarel).pdf
- Slide 12: mandrill the textbook (most sexually dimorphic) primate; male red coloration and secondary sexual adornments track testosterone and dominance rank. Sources: https://durham-repository.worktribe.com/output/1543130 ; https://pmc.ncbi.nlm.nih.gov/articles/PMC1636084 ; https://en.wikipedia.org/wiki/Mandrill
- Slide 13: males ~16% more body mass and ~65% more muscle mass — both figures as given in Lassek & Gaulin 2022 (Frontiers in Psychology; "∼16%" stature and body mass, "65% more muscle mass"); their 2009 paper gave 61%. US adults: males 16.5% heavier. Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9156798/ ; https://www.anth.ucsb.edu/sites/secure.lsit.ucsb.edu.anth.d7/files/sitefiles/people/gaulin/Lassek%20&%20Gaulin_muscle%20mass.pdf ; https://en.wikipedia.org/wiki/Sexual_dimorphism
- Slide 13: larynx grows under testosterone; vocal folds lengthen and thicken, lowering fundamental frequency; the "break" is the unstable transition. Sources: https://ncvs.org/?p=8649 ; https://en.wikipedia.org/wiki/Voice_change
- Slide 14: Tanner scale, five stages, rated separately for breast, genital and pubic-hair development; first sign in ~85–90% of girls is the breast bud (pubarche first in ~10%), in boys testicular enlargement (≥4 mL or ≥2.5 cm). Sources: https://medicinetoday.com.au/system/files/pdf/medicine_today/article/MT2007-05-026-CAMPBELL.pdf ; https://tidsskriftet.no/sites/default/files/2023-02/bruserudappendix1_eng_0.pdf
- Slide 15: HealthyChildren.org is the AAP's parent site; the page is credited to the AAP Council on Child Abuse and Neglect (2023); four columns as named above; "self-stimulation does not by itself indicate sexual abuse". Source: https://www.healthychildren.org/English/ages-stages/preschool/Pages/Sexual-Behaviors-Young-Children.aspx
- Slide 15: the lecturer's dislike of "normal", the rename to "warrants investigation/intervention", and "most of it is probably normal" — deck slide 15 verbatim.
- Slide 2: four objectives match deck slide 3. Slide 1: bio items (board-certified sexual medicine and occupational medicine physician, course director at the Northwest Institute on Intimacy, University of Washington, medical director of Rainier Occupational Clinic) match deck slide 2. Slide 1: "the last hour carried the body from a single cell to a newborn" matches lecture 2 (embryo plates, genital homologies, critical periods). Slide 9: both reasons to delay puberty match deck slide 9. Slide 16: closing prompt is deck slide 16.

## Could not verify (softened or removed)
- Slide 6: Tanner's "17 in the mid-1800s" could not be confirmed as a reliable figure (the Oslo re-analysis gives 15.6 in 1861); softened to "roughly 15 to 17" as above.
- Slide 15: "asking where babies come from" (not in the AAP table) removed; "knowledge of adult sexual acts beyond the child's stage" (not an AAP criterion) removed and replaced with the page's own criteria.

## Beats changed
- None. All 16 subjects checked against the envelope: every subject carries the no-text/labels/signage clause; no real-person likeness; the three human studies (slides 8, 9, 15) are adults, fully clothed, composed, with the full-portrait face clause, and slide 15 says "No children" explicitly; no minors anywhere (slide 3 is a bare abstract growth curve, slide 10 a femur with its growth plate for the Ashley slide, not a child); no nudity, restraints, blood or distress; anatomical plates (brain base, adrenal, neuron, chromosomes, femur, receptor, larynx, pelvis) are structures, not symptoms; the mandrill plate describes face and coat colouring only. `beats.json` parses, 16 beats, slides 1–16 in order matching the 16 `##` headings.

## For the editor's attention
- Deck slide 8 attributes "breast and endometrial cancers" and "greater all cause mortality" to the same evidence as the rest of the list, but the UK Biobank paper the list is drawn from has neither (it did not assess mortality). The script now separates them ("in other cohorts"). If the deck is revised, note the two sources. Also: every UK Biobank outcome is self-reported by recall, and the men's "voice breaking" timing was never validated; the paper itself says so.
- Deck slide 8's "low intelligence" is the UK Biobank's binary "Low intelligence (Fluid)" flag (≤2/13 on a 13-item test). It is a crude outcome and reads harshly aloud; the script now says "a low score on a test of fluid intelligence". The lecturer may prefer to drop it.
- Deck slide 6 says "since the 20th century"; the records run from the 1860s, and Tanner's famous 17-year Norwegian starting point is contested. Script softened to a range. "Complete slightly later" stands as the course's observation; the support (longer thelarche-to-menarche interval in Danish girls) is thinner than for the earlier onset.
- Deck slide 11 lists Camcevi under leuprolide acetate (it is the mesylate), treats all leuprolide products as sharing four indications (Camcevi and Eligard are prostate-only, Fensolvi CPP-only), and lists "Vantas Histrelin Implant" as current (discontinued September 2021; no prostate-indication histrelin implant exists now). Script corrected; deck should be.
- Deck slide 12 defines sexual dimorphism by sex chromosome. Fine for mammals, imprecise as a general definition (ZW birds, temperature-dependent reptiles); script says "according to their sex, which in mammals follows the sex chromosomes".
- Deck slide 13's 16% and 65% are exactly Lassek & Gaulin 2022's numbers; the 65% is muscle mass by their method, and their 2009 paper gave 61%. Defensible as stated ("about").
- Deck slide 15 points to HealthyChildren.org generically; the page's table covers ages 2–6 only. Script now says so. The script's red-flag sentence now includes "imitation of adult sexual acts" because it is one of the AAP's own criteria; it is clinical and brief, but it is one notch more specific than the deck.
- Deck slide 2 calls the lecturer a "board-certified sexual medicine physician"; there is no ABMS board in sexual medicine, and the credential meant is presumably the FECSM fellowship (European Committee of Sexual Medicine) the same slide lists. Left as the deck gives it, since it is her own bio.
- Mini-puberty: the "six months" figure is the boys' course; girls' FSH can stay elevated to 3–4 years. Script now says "more slowly in girls" without the number, to hold the budget.
- The Ashley paragraph is factual and neutral; it does not take a side, and it names no physician. The institution is given as "the Seattle children's hospital" rather than the current brand, because the events predate the rename.