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The Peter Attia Drive

The endocrine system: exploring thyroid, adrenal, and sex hormones | Peter Attia, M.D.

Mon May 29 2023

The Drive podcast

  • Focuses on translating the science of longevity into accessible content for everyone.
  • Offers a membership program for more in-depth content.
  • Covers the basics of various endocrine systems, including the thyroid system, adrenal system, and sex hormone system for both men and women.

Thyroid System

  • The thyroid gland is regulated by TSH from the pituitary gland, which is regulated upstream by TRH from the hypothalamus.
  • The thyroid gland produces mostly T4 and a little bit of T3, with T3 being the active version responsible for controlling various bodily functions.
  • Enzymes called diodenases convert T4 into T3, while D3 makes reverse T3 which blocks the effects of T3.
  • Fasting can cause a reduction in free T3 and an increase in reverse T3.
  • Evaluating a patient's thyroid status based solely on their TSH levels may not always be accurate.
  • High reverse T3 and low T3 levels can cause hypothyroidism symptoms even with normal TSH levels.
  • Standard treatment for hypothyroidism involves giving synthetic T4 hormone, but this may not work for all patients.
  • For patients with downregulated D1 and D2 enzymes that produce more reverse T3 instead of T3, it might be better to give them T3 directly.
  • Regular cyto-mel (T3) drug is difficult for patients to tolerate, so compounded control release T3 is used instead.
  • Desiccated thyroid is a common way patients receive T3 and T4.
  • There are competing schools of thought on which formulation to use for hypothyroidism treatment.

Adrenal System

  • Blood tests are not effective in measuring the adrenal system.
  • Free cortisol is what exerts biological activity and can be measured through a saliva or urine test.
  • The Dutch test is preferred as it measures free cortisol and cortisol metabolites.
  • Adrenal fatigue may not necessarily be caused by fatigued adrenal glands.
  • Low levels of free cortisol do not necessarily mean adrenal gland fatigue.
  • Patients with low free cortisol may have ample amounts of production but are degrading too much of their cortisol or turning it into inactive cortisone.
  • Enzymes called reductases regulate the conversion of cortisol and cortisone into their metabolites, which can be accelerated by inflammation, obesity, and poor health factors.
  • To reverse these factors, obesity, insulin resistance, leptin resistance, and underlying inflammation need to be addressed.
  • People with very high or very low levels of free cortisol may have symptoms associated with those things and need to check what's going on with their cortisone.
  • The rhythm of cortisol needs to be normal for optimal health.
  • If a person is really low in cortisol and symptomatic despite having plenty of cortisone, the enzyme 11 beta HSD needs to be flipped by addressing issues like insulin resistance, obesity, inflammation, low thyroid function, hyperthyroidism, progesterone imbalance or PCOS.
  • Adrenal support supplements made up of licorice root can help address these issues.
  • Phosphatidyl serine can be used to suppress cortisol production in the evening and facilitate sleep.

Sex Hormone System (Female)

  • Understanding the female reproductive system during the menstrual cycle can simplify understanding of sex hormones.
  • The menstrual cycle is divided into two phases: follicular and luteal.
  • Follicle stimulating hormone and estrogen dominate the follicular phase, preparing the body for ovulation.
  • Monitoring FSH and estradiol levels during day 3, 4, or 5 can indicate approaching menopause.
  • PMS symptoms may be caused by the rapid drop in progesterone levels after day 21, and can be treated with low doses of progesterone.
  • Women with regular cycles can take a low dose of progesterone for seven days after ovulation to reduce the dramatic reduction in progesterone levels and ameliorate symptoms.
  • Taking progesterone for 14 days or using oral contraceptives are alternative hormonal ways to address the issue.
  • Testosterone changes very little during the cycle, but women have five to ten times more testosterone than estradiol in their bodies even at peak estradiol level.
  • During menopause, women's bodies produce less estradiol and progesterone, leading to high levels of FSH and LH. Hormone replacement therapy should be initiated before flat line estradiol and progesterone levels occur.
  • Estrogen is the most important hormone in both men and women as it regulates bone building via osteoblasts.

Sex Hormone System (Male)

  • The male sex hormone system has upstream regulation at the hypothalamus via GNRH, which tells the pituitary to secrete LH and FSH that speak to the testes.
  • The testes have different cells that make testosterone, which is mostly bound to SHBG and albumin with a small amount remaining free or unbound.
  • Five alpha reductase enzyme converts some testosterone into dihydrotestosterone (DHT), which has a higher binding affinity for the androgen receptor than testosterone.
  • Aromatase enzymes convert some testosterone into estrogen, which is important for mood, body composition, and bone mineral density in men.
  • Testosterone levels inhibit the hypothalamus and pituitary gland, slowing down GNRH and LH/FSH production via a feedback loop.
  • Estrogen also inhibits luteinizing hormone secretion via the pituitary gland.
  • Only 1-3% of total testosterone is free and biologically active due to SHBG and albumin binding most of it.
  • Testosterone binds to an androgen receptor inside the nucleus of a cell, affecting transcription.
  • Measuring total testosterone alone is not enough to determine low T or need for testosterone replacement therapy as free T is a calculated lab value.
  • Low levels of testosterone can cause symptoms such as low libido, erectile dysfunction, low mood, difficulty putting on muscle mass, and insulin resistance.
  • Testosterone can improve insulin resistance, muscle mass, strength, body composition, and mood.
  • Treatment options for low testosterone include direct methods such as topical or injectable testosterone and indirect methods such as HCG or Clomid.
  • Chlo-mid blocks the effect of estrogen in the brain, which can have negative effects on mood.
  • High estradiol levels can have side effects such as gynecomastia, but they are typically only seen in people using excessive amounts of testosterone.
  • Anastrosol is a drug that blocks conversion of testosterone to estradiol, but it is not always necessary or recommended.
  • Testosterone replacement therapy should only be given if there is a biochemical and symptomatic case for it.
  • TRT should be stopped if the patient's symptoms do not improve after fixing their biochemical issue.
  • High testosterone and estradiol levels are important for men with osteopenia to maintain or increase bone mineral density.
  • Symptoms are more important than hormone levels for most men.
  • Removing testosterone may not worsen symptoms in some men who have low estrogen receptors or highly saturated estrogen receptors.
  • The male sex hormone system has nuances and complexities in diagnosis.

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  • The podcast is for general informational purposes only and does not constitute medical advice.