Hormonal physiology shifts predictably with age, but the magnitude and the response to intervention varies enormously by individual. This page is the navigational map for the more specific articles to come.
Men: testosterone across decades
Population data shows ~1% per year decline in total testosterone after age 30. The number matters less than the trajectory and the symptom load. TRT candidacy under most guideline frameworks (Endocrine Society, AUA) requires: (1) symptoms (fatigue, low libido, loss of morning erections, cognitive dulling, mood), AND (2) two separate morning total T readings below ~300 ng/dL, with free T and SHBG also in range.
Typical protocols use testosterone cypionate or enanthate, 100-200 mg/week split across 2 injections, with monitoring every 3-6 months for hematocrit (rising red cell mass is the most common management issue), estradiol, PSA (past age 40), and lipid panel. Expected symptomatic benefit: reversal of fatigue/libido within 4-12 weeks; body composition changes over 6-12 months.
Counter-view: Mohit Khera and others argue that "symptomatic but eugonadal" men (low-normal T with low-T symptoms) respond to clomiphene or enclomiphene restart approaches rather than exogenous TRT, preserving fertility. The fertility trade-off of exogenous T is real and under-communicated; anyone who might want biological children should know about it.
Women: perimenopause and menopause
Perimenopause spans ~4-10 years before the final menstrual period, with estrogen and progesterone variability driving the bulk of symptoms (hot flashes, sleep disruption, mood, vaginal atrophy, cognitive fog). The Women's Health Initiative (WHI) 2002 Manson et al. 2013, n=27347 halted mid-trial on concerns about breast cancer and cardiovascular risk with combined HRT. Subsequent reanalysis and more-granular follow-up ( Manson et al. (VITAL) 2019, n=25871 is methodologically comparable in scale though on a different question) has clarified:
- HRT started within 10 years of menopause has a favorable risk/benefit profile for most women.
- HRT started after 10 years post-menopause carries higher cardiovascular risk and is generally not recommended for symptom-only indications.
- Transdermal estradiol (patch, gel) has a lower VTE and stroke risk signal than oral formulations.
- Progesterone (not progestin) is preferred in most modern protocols.
Avrum Bluming and Carol Tavris's "Estrogen Matters" (2018) argues HRT is under-prescribed due to residual WHI fear. JoAnn Manson (a WHI investigator herself) agrees on the 10-year window but is more cautious on duration past age 65. Both camps agree the WHI message was over-interpreted in the early 2000s.
Thyroid
Annual TSH is often the only screen; it misses a meaningful minority of patients with normal TSH and low free T3/T4 or elevated reverse T3. Subclinical hypothyroidism (TSH 4.5-10 with normal T4) is usually watched, not treated, except during pregnancy planning or if TPO antibodies are positive. Overt hypothyroidism (TSH >10 or low T4) is treated with levothyroxine; T3 addition (combination T4/T3) remains debated; most guidelines don't endorse it routinely but a subset of patients report better symptom control.
Mannick 2018 (n=264) is the closest large trial on a hormone-adjacent pathway, showing TORC1 inhibition improved immune function in healthy elderly ( Mannick et al. 2018, n=264 ); the direct HRT and TRT literature is larger but older and less uniformly blinded.
Cortisol
"Adrenal fatigue" is not a recognized endocrine diagnosis. What is real: cortisol awakening response attenuation, flattened diurnal curve, and chronic mild hypercortisolism. The test to run if you suspect dysregulation is a 4-point salivary cortisol across the day, not a single morning blood draw.
Insulin
Already covered in the metabolism section. Fasting insulin + HbA1c + 2-hour post-prandial glucose catches far more early dysglycemia than HbA1c alone. Normal HbA1c does not mean normal glucose tolerance.
Testing frameworks
| Phase | Dose | Frequency | Notes |
|---|---|---|---|
| Men baseline | Total + free T, SHBG, estradiol, LH, FSH, prolactin, TSH, free T4, free T3, rT3 | annually | Morning (7-10am) fasting draw for T. |
| Women baseline | Estradiol, progesterone, FSH, LH, prolactin, DHEA-S, TSH, free T4, free T3 | annually + cycle-timed if pre-menopausal | Cycle day 3 for FSH; luteal for progesterone. |
| Cortisol | 4-point salivary: waking, noon, 5pm, bedtime | if suspicion of dysregulation | Single AM serum cortisol misses most patterns. |
| Trend marker | 1-2 of the above, repeated quarterly | quarterly | Trends matter more than single readings. |
The biological age angle
The Biological Age Estimator uses 9 markers from a standard CBC + CMP + CRP panel. Several overlap with the hormone discussion indirectly (inflammation, glucose, protein). Use it as one data point, not a verdict.
