A review of adverse events in animals and children after secondary exposure to transdermal hormone-containing medicinal products

Abstract

Background: Hormonal replacement therapy is widely used to treat conditions in humans, the most well-known indication being the relief of menopausal symptoms in women. Many of the hormone-containing products (HCP) are applied to the skin. This transdermal delivery poses a risk to animals and humans through secondary exposure, especially when product information is not strictly followed. The aim of this article is to raise awareness among veterinarians and human healthcare providers of this risk; based on evidence from spontaneous reporting of suspected adverse events (AEs) in animals and humans. Interventions are also explored to mitigate the risk of secondary exposure to transdermal HCP (THCP).

Review of spontaneously reported suspected aes: The Swedish Medical Products Agency has received several, mainly serious, AE reports in animals and children following secondary exposure to THCPs. The AE reports were reviewed together with worldwide data from the EudraVigilance Veterinary database and human EudraVigilance Data Analysis System. The clinical signs reported in animals included persistent signs of oestrus, poor growth rate and birth defects. In humans, reported clinical signs included precocious puberty, unresolved virilisation, accelerated growth rate and female infertility.

Conclusions: It is important that THCP are used according to manufacturer's instructions and users are made aware of risks and mitigating measures. This review of AEs in animals and children provides evidence to show that the use of THCP poses a risk for secondary exposure. Efficient communication strategies that stretch across veterinary and human medicinal disciplines are required to raise mutual awareness and minimise the risk of AEs in animals and humans.

FIGURE 1

Symmetrical alopecia in a 6‐month‐old, entire male, Rhodesian ridgeback dog following secondary exposure to a transdermal oestrogen‐containing product. (a) Symmetrical alopecia of the pectoral region. (b) Alopecia of the dorsal aspect of thigh. Full details are found in report 1 in the main text.

FIGURE 2

An 8‐week‐old, wire‐haired Dachshund before and after secondary exposure to a transdermal oestrogen‐containing product. (a) Mammary hypertrophy, hypertrophied abdominal skin, hanging preputium and bilateral non‐palpable testes following long‐term secondary exposure to a transdermal oestrogen‐containing product (HRT) which was used by the animal's owner. (b) One year after withdrawal of the HRT in the animal owner. The clinical signs show almost complete resolution. Full details are found in report 2 in the main text.

FIGURE 3

Enlargement of mammary glands in a 12‐week‐old, entire male, Sphynx kitten. The kitten developed clinical signs shortly after introduction into a household where the owner was using a transdermal oestrogen‐containing spray product. Full details are found in report 3 in the main text. The picture is an extracted frame from a video with poor resolution. A segment of the video has been made available as Supporting Information S1.