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Opponents including PhRMA, the Partnership for Safe Medicines, and the American Pharmacists Association each opposed inclusion of all seven substances on similar grounds

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With the exception of relugolix combined tablet, their use presents the risks of side-effects associated with GnRH agonists/antagonists (hot flashes, sleep disturbances, vaginal dryness, depression and loss of bone mass) and clinical recommendations encourage the use of add-back therapies to mitigate them, such as tibolone

[1] It binds copper ions and hands them to copper-using enzymes needed for collagen cross-linking (lysyl oxidase) and antioxidant defense (SOD)

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