Induction of Puberty in Adult Endocrinology:What do I need to know?

Kate Lissett

Torbay Hospital

Induction of puberty in adults

• Who• When• How• Hazards

Who

• Which doctor?• Which patient?

• How many of you have been involved in taking patients through puberty.........

• Can anyone give a brief case history......

AM

• 18.5 years• Attending Cardiology for regular follow

up of VSD, PMH IUGR.• Referred 18 months ago with primary

amenorrhoea, but failed to make /attend appointments due to embarrassment.

• Also complains of lack of breast development.

• On examination:• Very limited axillary and pubic hair,

breasts stage 2• External genitalia normal, P.V. not

performed• Trans abdominal ultrasound; v small

uterus, ovaries could not be identified.• Bloods LH 80, FSH 60, estradiol 44• Karyotype repeated (had been done at

birth) normal

CA

• 33 years• Presented on acute medical take with severe heart

failure. • Investigations go on to reveal severe AR and dilated

aortic root. Clinical evidence suggestive of previously undiagnosed Turners syndrome. Goes on to have composite aortic valve and root replacement.

• Now attending clinic, with a view to further endocrine management (NB karyotype mosaic, 46 X with an isodicentric Y (dominant cell line) and 45 XO )

What is normal

Stages of Pubertal Development

Pubertal Sequence

Accelerated growth→breast development→adrenarche→menarche

• requires 4.5 years (range 1.5 to 6 years)

Signs of Puberty: Tanner Staging

Stage 1 (Prepubertal)

Elevation of papilla only. No pubic hair.

Stage 2 Elevation of breast and papilla as small mound, areola diameter enlarged. Median age: 9.8

Sparse, long, pigmented hair, along labia majora. Median age: 10.5

Stage 3 Further enlargement without separation of breast and areola. Median age: 11.2

Dark, course, curled hair sparsely spread over mons. Median age: 11.4

Stage 4 Secondary mound of areola and papilla above the breast. Median age: 12.1

Adult type hair, abundant but limited to mons. Median age: 12

Stage 5 Recession of areola to contour of breast. Median age: 14.6

Adult type spread in quantity and distribution. Median age: 13.7

Tanner Staging

How....

• What estrogen• At what dose• How would you monitor

Be aware

• Emotional /psychological as well as physical impact

Difficulties/Risks

• Drug availability – prescribe in secondary care

• Prescription of “adult dose” estrogens by non specialist

• May have long term impact on breast /uterine development

• Psychological implications

Men

Do you have any case histories

PC

• 23 years• Referred by GP , as couple have

primary infertility• Patient denies any symptoms or signs• On examination, eunachoidal

phenotype, 5’10’’, prepubertal• Further investigation suggests

hypogonadotrophic hypogonadism

What are the aims of treatment

What options do you have in this man to induce puberty?

• GHRH pump – not something I’ve used but available at some centres

• 200-500 IU (c.f. Adult doses of 1250–5000) hCG – will normalize testosterone levels and induced testicular growth.

• Cost and need for regular injections means this is not usual option, but may be appropriate in some circumstances.

Induction of puberty using testosterone esters

• Increasing dose schedule every 6 months:• 50 mg monthly i.m.• Increased approximately every 6 months• Adult dose Sustanon 250 per 3–4 weeks• Imperfect – first pass metabolism and profile

over month not good.• Gel seem an ideal alternative – but I am not

aware of specialist centres using as yet.....• Inducing puberty with testosterone rather than

hCG does not appear adversely affect fertility.

And for fertility

• Most patients with IHH and KS require a combination of hCG and FSH to stimulate sperm production.

• The starting dose for hCG is 1000 IU, and FSH is 75-150 IU alternate days

• Dosage adjusted based on trough T level, testicular growth, sperm production, and avoidance of adverse effects (monitored every 3 months)

• Gynecomastia common - 30%

• Monitor every 3 months until an adequate level of replacement is documented.

• Pregnancy has occurred with counts as low as 2.5 X 106, but 20-40 X 106/mL produces higher pregnancy rates.

• Median time to induction of spermatogenesis is 6-8 months – may take 2 years.

• Remember to cryopreserve sperm should fertility be achieved.

• Safer and cheaper to than IVF for couple.