Notes from the lecture: (no way am I spelling everything correctly)

There are many causes for infertility, not only metabolic, but there are metabolic pathways that lead to male infertility. It is speculated most incidences are rooted in metabolic dysfunction)

Common metabolic core between roots of infertility between men and women. About 30% of infertile couples are infertile due to male infertility.

Several Hormones involved, not just a problem of estrogens or androgens. Other hormones setup the production of these, so there is a fanout. Male hormones tend to be more consistent at a low level.

FSH - folical stimulating hormone LSH - Lutinizing stimulating hormone

Both relevant in men, not just women, even though the names are based on women physiology.

Male Reproductive Function - Endocrine signaling - Normal pathways.

FSH stimulates spermatogenesis (testes producing sperm) - production and maturation. Two distinct testie cell types (that have female analog to ovaries) - certolie cells - FSH impacts tubules/carrying structures - regulation and growth.

LSH - Ledig cells - promote production of testosterone - there are myriad androgens but testosterone is most well known.

Testosterone - promotes libedo, plays into sex drive of both sexes, but men with higher testosterone have higher sex drive (libedo). Works in tandem with FSH to promote spermatogenesis. Paracrin signaling - with certolie cell. Drives erections, via enhancing nitrous oxide which is a key mediator of erections.

Nitric Oxide - All about blood flow. vasodilatory effect. Increases blood flow by expanding blood vessels. Also relevant in exercise (local increase in nitric oxide to feed muscles via more blood flow).

Insulin is a super hormone, it effects literally every signal cell in the body, including endothelium cells (blood vessel lining) they respond to insulin by producing nitric oxide synthesis. (One intervention for heart attack victims is to apply nitroglycerin under the tongue, which dissolves into the blood stream as a precursor to nitric oxide inducing vasodilation increasing blood flow everywhere, helping to resolve the immediate infarction).

Insulin’s normal effects is to increase the production of nitric oxide, to increase vasodilation, but as endothelium becomes insulin resistant it is less capable of producing nitric oxide. Leading to compromised blood flow (increased blood flow everywhere) but specifically erectile disfunction - the most common form of infertility in men.

Low Testosterone - Has become very common in the zeitgeist (lots of social media attention). Insulin resistance is significantly associated with decreased decreased testosterone production, primary a direct effect on ledig cells which are primarily responsible for testosterone synthesis.

Low Testosterone impacts insulin signaling in the body, creative a vicious positive feedback loop.

Testosterone enhances insulin signaling, increases the expression of key proteins involved in the pathways. IRS1. GLUTE4 (glucose pathway) - critical for insulins action in muscle and adipose, to regulate blood glucose levels. Also has a lipolidic effect, testosterone decreases visceral fat levels. Can also lower levels of inflammatory markers, which is causal for lower levels of insulin sensitivity.

Insulin Resistance - Decrease lidic cell testosterone secretion, independent of LH (suggesting direct insulin resistance in the testes). Steroidogenic pathway (production/activation of steroid pathways) - All sex hormones come from cholesterol - which comes from steroid nucleus. The backbone for all steroid hormones are built on, sex hormones but others like aldosterone (water/electrolyte regulation).

• Insulin Resistance -> Lower Testosterone Production
• Lower Testosterone Production -> More Insulin Resistance

Insulin Resistance - Increased testosterone conversion, aromatization, converting testosterone to estrogens. Normal process in men (and women). Men typically have low levels of aromatization, but when Insulin Resistant… Fat cells have the ability to express aromatize. As men store more fat, especially in abdominal area, the fat acts more and more like ovaries. Ovaries (in women) are very aggressive converting testosterone into estrogens… But when insulin resistant, men began to mimic this pathway because the fat cells are elevating aromatize, converting testosterone into estrogen. Facilitating into weight gain, insulin resistance, sperm production, libedo. Sex hormones largely dictate WHERE we store fat, as males increase estrogens, can start to store fat into “female areas” (breasts, hips, butt) [man boobs].

Treatment:

• Lower insulin
• Shrink Fat cells

Any method that can do both will help. Testosterone will climb, sperm production will improve.

Diet impacts hormones, and impacts sperm quality. Any diet that moves away from the standard american diet (SAD) will improve their insulin sensitivity.

However, low fat diets, or diets without animal protein, have been indicated in two studies - testosterone decreases, and sperm quality decreases (but this is probably still a net positive compared to the SAD diet). If a man can’t resolve fertility issues with a low fat, or no animal protein diet, they could add them back in for better effect.

Wilson, 2017 - https://doi.org/10.1519/JSC.0000000000001935 - Resistance Trained Athletes following SAD (western diet)/ketogenic diet. Lean body mass gained in both - Ketogenic diet saw a significant increase in total testosterone compared to the SAD group.

Anyway to improve insulin sensitivity improves metabolic health - Anyway you can do it.

Testosterone measurements (and testosterone therapy) are not a health goal, its a indicator of metabolic issues, and the solutions should be based in improving the metabolism/insulin sensitivity

Medication - A insulin sensitizing medication, that improves insulin sensitivity (Not just blood glucose levels) - like metformin has been shown (and being explored) as a intervention for male infertility

Resistance exercise has been shown to improve markers of male fertility and performance, through antiinflammatory and antioxidant mechanism. If you don’t have time for cardio and resistance training, do resistance as the priority.