Outside of structural damage to the peripheral nerves and circulation that closely serve the reproductive organs such as what may occur with diabetes neuropathy and vascular disease, libido and erectile dysfunction are brain problems.

Within the brain, are specific circuits that need to be active for libido (and erectile function). Some circuits involved include:

• the libido circuit (amygdala, the bed nucleus of stria terminalis, the hypothalamus preoptic are and ventromedial nucleus, the periaqueductal gray),
• the seek circuit (nucleus accumbens to ventral temental area, hypothalamus medical and perifornical zones) to periaqueductal gray),
• the care circuit (anterior cingulat, bed nucleus of straia terminalis, preoptic hypothalamus, ventral tegmental area, periaqueductal gray), and
• the joy circuit (diencephalon, parafascicular area, periaqueductal gray).

In addition, other circuits which can negate libido need to be suppressed. These include the anger, fear, and panic circuits.

Additionally, the sensory-motor strip which processes the sensory information from the reproductive organs and other erogenous zones needs to be an active and metabolically robust group of brain cells – otherwise the mental representation and sensitivity of the organs and erogenous zones will be reduced. Memory circuits and motor circuits are also recruited to process and store information about sex.

This is where the lack of sexual activity or masturbation can be destructive since number of brain cells devoted to sex diminishes. The brain’s representation of the penis shrinks without use. With age and programmed death of cells that aren’t used, the number of cells devoted to sex diminishes.

The brain is a use it or lose it system. This is one way men feel their penises are shrinking and become insensitive when they stop engaging in sex, when the penis remains physically the same size when erect. Practice is necessary to maintain libido, even when one doesn’t have a libido. Penis exercises may need to be done if one doesn’t have libido in addition to optimizing physiology in order to improve the number and activity of cells devoted to sexual function.

There are numerous signals that can turn on the libido circuit, not just testosterone. There are numerous signals that turn off the libido circuit. Each of the main circuits has numerous signals that turn them on and turn them off. The circuits also need to have adequate nutrition and energy production to function.

Thus if testosterone, estrogens, thyroid hormone, and DHEA are already optimized, and if problems with libido are still present, then problems are occurring in other areas.

Some of the signals affecting the libido-related circuits include:
• ACTH
• aldosterone
• cholecystokinin
• cortisol
• corticosterone
• CRH
• DHEA
• dihydrotestosterone
• dopamine
• estrogens
• GABA
• glutamate
• growth hormone
• leutenizing hormone-releasing hormone
• melanocyte stimulating hormone
• neurotensin
• norepinephrine
• endogenous opioids
• oxytocin
• pro-inflammatory cytokines (e.g. IL-1b, IL-6, Tumor necrosis factor, etc.)
• progesterone
• prolactin
• serotonin
• testosterone
• thyroid hormone
• vasopressin

Note that hypothalamic-adrenal dysregulation is a brain problem, not an adrenal problem in nearly all patients. My preference is to address the brain problems as directly as possible. Adding exogenous cortisol can be a problem since it shuts down production of many signals that have a positive effect on the libido-related circuits, including ACTH, progesterone, corticosterone, MSH, endogenous opioids, etc.

Nutrition has to be optimized. Without adequate iron, for example, dopamine can’t be produced. Assessing iron metaboism not only needs Ferritin, but also serum Iron, CBC, Vitamin A, Copper, etc. etc.

SHBG is a small player (which also means free Testosterone is a small player). There are more important considerations. It’s level is determined by more than 6 different hormones which can go in opposite directions. Insulin, is the strongest signal and it suppresses SHBG production. Outside of insulin and over-physiologic levels of testosterone, what level of SHBG one has doesn’t tell much about what problems there are with the hormones that influence it. A normal SHBG doesn’t tell if there are problems with these hormones since the problems can negate each other’s effect on SHBG. Once excessive insulin signaling is addressed and total testosterone is optimized, my preference is to look for more important problems than SHBG issues when it comes to libido.