## 4 Discussion
At present, ingredients of animal origin are used less frequently for various reasons, including the risk of infectious contaminations, and legal restrictions, but also to ethical issues and concerns about animal welfare and the protection of biodiversity [94; 95]. The use of animal by-products in the cosme industry is only permitted if they meet the requirements of purity, safety and hygiene [95]. For safety reasons, they often are replaced with similar plant or synthetic substances. In addition, consumers often pay attention to certifications of products as vegan or cruelty-free [96; 97]. A range of animal ingredients that were used in cosmetics in the past are abandoned now because modern research has failed to demonstrate their effectiveness or found unacceptable risks to consumers' health [98]. The FDA recommends that placenta-derived ingredients which for safety reasons are depleted of hormones and other biologically active substances should not be identified as \"placenta extract\" because it may be misleading to consumers who associate the name with certain biological activities [22]. In Singapore, the human placenta is readily available from China in a dried form and broadly used to treat baldness. In addition to restoring hair growth, human placenta extract was found to be effective in reducing wrinkles and strengthening the immune response [9]. Injections of placenta extract have been used with some success in women with hair loss and other cosmetic applications [99]. Human placenta extract was also shown to induce hair regrowth after chemotherapy-induced alopecia, possibly due to inhibition of apoptosis and stimulation of proliferation in hair follicles [100]. An ex vivo study in human scalp samples sourced from facelift surgery demonstrated the ability of human placenta extracellular matrix (HPECM) hydrogel to regenerate hair follicles and induce hair growth [101]. The overall impression from the present systematic review is that very limited clinical evidence is available to date for the effectiveness of placenta products against hair loss in humans. In the entire literature, we could identify a mere three clinical trials that met the inclusion criteria, all studied exclusively animal (bovine, equine, and porcine) placenta derivatives. Moreover, a complex mixture of equine placental growth factors with pumpkin extract, panthenol, and niacinamide was tested in one of the trials in an uncontrolled manner, making any assessment of placenta effects virtually impossible [82]. One of the components in the mixture--niacinamide, contrary to expectations, might actually inhibit hair growth thus possibly counteracting the putative effects of other ingredients [102; 103]. There are also four recent animal studies (three in mice, one in rats) with a design similar to the human trials, among them one of human placenta extract [104]. All four animal studies were controlled with minoxidil (Table 5). Altogether, the results from animal research suggest that the effects of placenta products on hair growth are comparable to minoxidil. Nevertheless, when looking at these data, one has to keep in mind the significant morphological and physiological differences between human hair and that of laboratory animals [107]. Moreover, laboratory models of hair loss used in these studies like fur shaving or chemical depilation have little in common with effluvium or alpeccia in men and women. Natural materials such as placenta products are mixtures of various compounds. Therefore, it is difficult to ascribe observed effects to particular placenta compounds and single out involved metabolic pathways. Moreover, various components may act synergistically or--on the contrary--mutually block their effects. More studies are needed to understand the complex mechanisms of the placenta's influence on the hair and scalp. The available data are insufficient to confirm the safety of placental derivatives in cosmetics, hence many restrictions on their use.