Oestradiol Matters for Everyone

All sexes rely on oestradiol to keep the brain, bones, muscles, metabolism, and cardiovascular system healthy. But only females experience a sudden, dramatic loss at midlife. Understanding this distinction helps explain why:

• Why the climacteric (perimenopause, menopause & postmenopause) can feel so disruptive

• Why symptoms can appear in any system of the body

• Why female midlife health risk increases across bone, cardiovascular, metabolic, and neurological domains

• Why male ageing is hormonally different

• Why stigma and misunderstanding persist
  

This knowledge can help people to recognise symptoms early, seek appropriate support, and better understand what their bodies are experiencing during this major neuroendocrine transition.

Oestradiol molecule diagram (Da Silva et al. 2003)¹

Many hormones help the body adjust to changing needs. One of the most important is oestradiol (E2), a hormone essential for healthy development and lifelong homeostasis in all sexes, female, male, and gender-diverse individuals.

Oestradiol (E2) is the most potent and biologically active member of the oestrogen family, which also includes oestrone (E1) and oestriol (E3). Although it is often labelled a “female hormone,” this description is misleading. In reality, oestradiol is a core regulatory hormone with effects that reach far beyond reproduction.

Across all sexes, oestradiol plays a major role in:

• bone growth during puberty

• epiphyseal (growth-plate) closure, which completes height development

• lifelong bone remodelling

• muscle maintenance

• vascular flexibility

• immune regulation

• brain energy metabolism, synaptic function, temperature control, and mood regulation

The Key Difference: How Oestradial Changes With Age

The most profound sex difference is not its importance, but how its production changes across the lifespan.

In females

Oestradiol is produced mainly by granulosa cells in the ovaries. During the climacteric transition (perimenopause → menopause), these cells become inactive, and oestradiol levels fall abruptly, often by more than 60–90% over a relatively short period^1,5.

Once ovarian oestradiol production stops:

• oestrone (E1) becomes the main circulating oestrogen

• E1 is 4–10 times weaker at oestrogen receptors

• local conversion of E1 to small amounts of E2 occurs but is slow and insufficient

• the body can no longer maintain the stable pre-menopausal equilibrium

This sudden loss affects every system that relies on oestradiol, including the brain. Research shows measurable changes in brain structure, connectivity, thermoregulation, and energy metabolism during this transition⁴. These brain-level shifts help explain common symptoms such as:

• hot flushes

• poor sleep

• brain fog and memory lapses

• mood changes

• increased inflammation

• weight gain or body-composition changes

• 
  

The body eventually stabilises at a new, lower baseline, but the abrupt drop can accelerate:

• bone loss (osteopenia → osteoporosis)

• muscle loss (sarcopenia)

• vascular stiffening

• thermoregulatory instability

In males

Males do not experience an ovarian shut-down. Instead, aromatase, an enzyme in the testes, fat tissue, bone, brain, and blood-vessel lining, converts some testosterone into oestradiol. This process (aromatisation) continues throughout life.

Ageing males experience a slow and gradual decline in hypothalamic drive and testosterone, leading to a gentle reduction in oestradiol. This gradual change allows for metabolic and neuroendocrine stability, without the system-wide disruption seen in the abrupt ovarian transition that females experience.

However, men are not immune to problems. Conditions such as obesity, chronic inflammation, long-term illness, or certain medications (e.g., opioids, glucocorticoids) can cause pathological hypogonadism, where testosterone and oestradiol fall below healthy ranges³. This can impair bone density, metabolic function, fertility, sexual function, and mood.

By understanding the central role of oestradiol in all sexes, and the unique midlife decline experienced by women, we can begin to bridge the gap between scientific knowledge and real-world experience. This awareness is a vital step toward better education, earlier recognition of symptoms, better health care, and more equitable support across the lifespan.

References

1. Burger, Henry. (2006). Physiology and Endocrinology of the Menopause. Medicine. 34. 27-30. 10.1383/medc.2006.34.1.27.
   

2. Da Silva, E, Valmalle, C, Becchi, M, Cuilleron, CY & Coleman, AW 2003, ‘The Use of Electrospray Mass Spectrometry (ES/MS) for the Differential Detection of Some Steroids as Calix-[n]-arene Sulphonate Complexes’, Journal of Inclusion Phenomena and Macrocyclic Chemistry, vol. 46, no. 1–2, pp. 65–69.
   

3. Kaufman, J-M, Lapauw, B, Mahmoud, A, T’Sjoen, G & Huhtaniemi, IT 2019, ‘Aging and the Male Reproductive System’, Endocrine Reviews, vol. 40, no. 4, pp. 906–972, <https://academic.oup.com/edrv/article/40/4/906/5381905>.
   

4. Mosconi, L, Berti, V, Dyke, J, Schelbaum, E, Jett, S, Loughlin, L, … Brinton, RD 2021, ‘Menopause impacts human brain structure, connectivity, energy metabolism, and amyloid-beta deposition’, Scientific Reports, 10867, vol. 11, no. 1.
   

5. Sowers MR, Zheng H, McConnell D, Nan B, Harlow SD, Randolph JF Jr. Estradiol rates of change in relation to the final menstrual period in a population-based cohort of women. J Clin Endocrinol Metab. 2008 Oct;93(10):3847-52. doi: 10.1210/jc.2008-1056. Epub 2008 Jul 22. PMID: 18647803; PMCID: PMC2579642.