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On the other hand, low estrogen can lead to various symptoms such as vasomotor issues , weight gain, increased risk for bone loss and even an increased risk of cardiovascular disease. When the NO cGMP pathway is activated, as occurs with sexual stimulation, inhibition of PDE5 by sildenafil results in increased corpus cavernosum levels of cGMP. The PKG inhibitor KT 5823 blocked the relief of spinal allodynia induced by resveratrol, a SIRT1 activator. Some of the major causes of ED are decreasing testosterone levels, using certain drugs that have ED as side effects, smoking or excessive use of alcohol and drugs, aging.