Review Nonurological uses of botulinum toxin in gynaecology
Authors Akila Anbazhagan / Ralph Roberts
• Botulinum toxin is a powerful neurotoxin which causes temporary ﬂaccid muscle paralysis. • A number of potential gynaecological applications have been described in addition to the well-established uses in urogynaecology.
• To understand how botulinum toxin works. • To learn about the preparations available and their contraindications and side-effects. • To be aware of the potential uses of botulinum toxin in the treatment of vaginismus and other gynaecological pain syndromes.
• Many of the uses described are still essentially experimental, although largely accepted into mainstream practice: does this need to be acknowledged when counselling women? Keywords botulinum toxin / chronic pelvic pain / vaginismus / vulvar vestibulitis / vulvodynia Please cite this article as: Anbazhagan A, Roberts R. Nonurological uses of botulinum toxin in gynaecology. The Obstetrician & Gynaecologist 2008;10:75–79.
Akila Anbazhagan MRCOG Specialist Registrar Department of Obstetrics and Gynaecology, Royal Jubilee Maternity Hospital, Grosvenor Road, Belfast BT12 6BJ, UK Ralph Roberts MD FRCP MRCOG Consultant Obstetrician and Gynaecologist Department of Obstetrics and Gynaecology, Ulster Hospital, Dundonald BT16 1RH, UK Email: firstname.lastname@example.org (corresponding author)
© 2008 Royal College of Obstetricians and Gynaecologists
The Obstetrician & Gynaecologist
Botulinum toxin is a neurotoxin produced by the Gram-positive, rod-shaped, anaerobic bacterium, Clostridium botulinum. It is known to cause botulism, a type of food poisoning that results in ﬂaccid muscle paralysis and death. It was ﬁrst isolated in 1897 by the Belgian scientist Professor Pierre Emile van Ermengem.1 There are seven different serotypes of botulinum toxin (A, B, C1, D, E, F, G), each exhibiting different properties. Botulinum toxin type A is the most studied of the serotypes and it is this serotype that has found therapeutic use.
Products for clinical use
Botulinum toxin is produced under controlled laboratory conditions and is given in extremely small therapeutic doses. Botulinum toxin type A received US Food and Drug Administration approval for the therapeutic treatment of strabismus and blepharospasm in 1989 and for the cosmetic treatment of glabellar wrinkles in 2002.3 It is available in two different preparations: Botox® (Allergan Ltd, Marlow, Bucks, UK) and Dysport® (Ipsen Ltd, Slough, Berks, UK). Doses of both products are quoted in mouse units (the amount of toxin that kills 50% of a group of 18–20 g Swiss–Webster mice). Botox appears to be the more potent—Botox 1 unit being equivalent to Dysport 3–5 units.4 While a vial of Botox contains 100 units, a vial of Dysport contains 500 units.
Mechanism of action
Botulinum toxin acts by blocking the release of acetylcholine at the neuromuscular junction, resulting in a chemodenervation that causes a temporary ﬂaccid paralysis (Figure 1).2 In an initial binding step, the toxin attaches rapidly and avidly to receptors on the cell surface membrane of the presynaptic nerve. It then becomes internalised by crossing the presynaptic nerve membrane. Finally, the toxin disrupts the calcium-mediated release of acetylcholine, thereby diminishing the endplate potential and causing paralysis. It does not affect postganglionic cholinergic or sympathetic transmission. Recovery of impulse transmission occurs gradually, as new nerve terminals sprout and contact is made with the postsynaptic motor endplate, a process that takes a few months. MUSCLE CNS
Contraindications and side-effects
Women referred for botulinum toxin therapy require full evaluation of the...