DBA UK 14 th Anniversary Conference 17 th -19 th May 2013 Hormonal and fertility issues caused by transfusion Dr Scott Akker Consultant Endocrinologist St Bartholomew’s Hospital London

The Endocrine/Transfusion interface Growth and sexual development Diabetes Thyroid and Parathyroid Bone Gonad (Testis and Ovary) Adrenal

The pituitary gland – the control centre

The pituitary controls the function of the ovary and testis GnRH – Gonadtrophin Releasing Hormone LH – Luteinising Hormone FSH – Follicle Stimulating Hormone

LH and FSH in men 1)LH drives Leydig cells to make testosterone 2)FSH drives Sertoli cells to make sperm Testis therefore has 2 separate but linked roles: - make hormone (testosterone) - make spermatozoa

LH and FSH in women Ovary therefore has 2 separate but linked roles: - make hormone (oestrogen & progesterone) - make oocytes LH drives hormone production and stimulates ovulation FSH drives follicle development Hormones allow the womb lining to develop

Iron overload Damage Testosterone Oestrogen Progesterone Damage can occur at level of: 1)Pituitary 2)Testes & Ovary

Pituitary/Testis damage in men Testosterone Oestrogen Progesterone Symptoms best treated by replacing the missing testosterone: 1)Daily testosterone gel (Testogel, Testim) 2)Testosterone injections (Nebido every 3 months) BUT there will be no sperm production

Pituitary/Ovary damage in women Testosterone Oestrogen Progesterone Symptoms best treated by replacing the missing oestrogen & progesterone: 1)A combined oral contraceptive preparation 2)A preparation usually used for post-menopause BUT there will be no egg production

Fertility/Men For men: –If requiring testosterone, unlikely to be producing sperm –If there is damage to the testes, may be unable to produce sperm –If there is pituitary damage, the testes may be able to produce sperm by replacing the LH and FSH

LH & FSH replacement Intensive Expensive Takes at least 3 months to produce a sperm and on average 6 months for a couple to get pregnant so at least a year of treatment May require additional help (IVF, ICSI, etc.)

Fertility/Women Difficult decision and discussion –Overall health important –Heart will have to do 40% more work –Diabetes adds to risks If damage to ovaries, may not be able to ovulate Clomiphene can help ovulate with careful monitoring May need additional help (IUI, IVF, ICSI)

Other fertility treatments/ IUI IUI – Intra-uterine insemination Sperm are placed directly into the uterus (womb) with a small tube/catheter

Other fertility treatments/ IVF IVF – In- Vitro Fertilisation Eggs are collected after Ovary stimulation The egg and sperm are mixed in a test tube An embryo is then placed directly into the womb

Other fertility treatments / ICSI ICSI – Intracytoplasmic Sperm Injection Eggs are collected after Ovary stimulation A single sperm is chosen and directly injected into a single egg The embryo is then placed directly into the womb

Fertility summary Fertility is a complex area and treatment will be limited by the amount and type of damage and cost Keeping low iron levels throughout life gives the best chance of not having problems with fertility It is possible that, like the heart, some of the damage to the endocrine organs is reversible with good chelation.

Bone Growth & Strength Multiple factors (Anaemia, Iron, Chelators, Growth Hormone deficiency/resistance) Also reduced by steroids Widespread Vitamin D deficiency –From sunlight! Absorbs calcium from gut Vitamin D easily replaced –Adult dose 25mcg/1000 units once daily (less in pregnancy and children)

Underactive Thyroid Thyroid gland makes thyroxine Easily replaced with tablet or liquid thyroxine Correct dose found by measuring free thyroxine level in the blood (fT4). BUT TSH must be ignored (if iron)

Adrenal Failure/Steroids Very rarely due to iron overload If on steroid treatment or replacement –Steroid card & Medic Alert –Emergency access to steroids if vomiting –Understand when to increase dose (eg)