Chromosomal sex vs Endocrinological sex

Public conversations about sex and gender often rely on oversimplifications with one of the most common being the idea that chromosomes alone determine a person’s sex “for life.”

This claim is inconsistent with contemporary biology, which recognises sex as a multidimensional system shaped by genetics, hormones, anatomy, and lived physiology across time.

A useful way to conceptualise this is to view chromosomes as an installer program, directing early developmental processes, while hormones serve as the active, continuously running software of the body.

Medical transition, in this framework, is a system update, altering the body’s ongoing biological processes in meaningful, measurable ways.

This analogy aligns with established scientific literature.

The role of chromosomes in embryonic development

Chromosomal sex (XX, XY, or variations such as XXY, XO, etc.) provides a template that influences:

• gonadal differentiation
• development of internal and external genitalia
• certain neurodevelopment pathways

However, these effects occur primarily during specific developmental windows – notably early gestation and puberty.

After development:

• nearly every cell contains a full set of chromosomes,
• but the vast majority of genes are silenced, and
• day-to-day bodily regulation is governed by endocrine signalling, not chromosomes.

Endocrine physiology uses circulating hormones – not the presence of XX or XY – to regulate adult tissue function

Most adult sex-differentiated traits (fat distribution, skin texture, libido patterns, metabolic rate, hair growth) are hormonally maintained, not genetically maintained.

Thus, chromosomes operate much like an installer: they set up the system, but do not actively run it.

Hormones regulate adult physiology. Hormones influence:

Endocrine physiology uses circulating hormones – not the presence of XX or XY – to regulate adult tissue function

Most adult sex-differentiated traits (fat distribution, skin texture, libido patterns, metabolic rate, hair growth) are hormonally maintained, not genetically maintained.

Thus, chromosomes operate much like an installer: they set up the system, but do not actively run it.

• metabolism and fat storage
• muscle composition
• skin and hair behaviour
• mood, cognition, and emotion regulation
• libido and sexual behaviour

These are dynamic, ongoing processes.

Trans women often report cyclic changes in:

• mood,
• libido,
• appetite,
• bloating,
• temperature sensitivity.

These “pseudo-cycles” or “ghost cycles” are consistent with:

• progesterone and estradiol fluctuations influencing the central nervous system
• hormonal impacts on thermoregulation and hydration

A uterus is not required for hormonal cycles to influence the brain or peripheral tissues. This illustrates that the software pattern, not the hardware presence, generates many cyclical experiences.

Hormone therapy produces predictable physiological changes

Feminising hormone therapy consistently produces:

• breast growth
• body-fat redistribution
• reduced muscle mass
• skin softening from changes in collagen structure
• changes in libido, emotional range, and affective processing

These changes occur regardless of chromosomal makeup, because adult tissues are responsive to circulating hormones.

The body “runs” the operating system it is currently receiving. Since endocrine signalling is the active regulatory system:

• when a trans woman begins estrogen and progesterone,
• and testosterone is suppressed,
• the body shifts into a new hormonal state that remodels physiology over months and years.

The system is no longer executing the original “installer instructions.” It is operating under a new configuration. This is fundamentally what “transition” means in biological terms: a change to the body’s actively running endocrine state, which in turn reorganises tissue behaviour, emotional patterns, and lived physiology.

Chromosomes do not override present hormonal reality.

There is no mechanism by which chromosomes can “force” an adult body to behave in a male-typical way if testosterone is suppressed and estrogen is dominant.

Endocrinologists have documented that hormonal milieus, not chromosomes, govern secondary sex characteristics.

Thus, the installer is no longer relevant to the functioning system.

Modern biology supports a process-based model rather than a static binary one.

• Genetics influence development.
• Hormones regulate real-time physiology.
• Anatomy is adaptable.
• Brain structures respond to hormone levels throughout life.
• Sex is multidimensional and partly plastic.

The installer/software analogy reflects this complexity without sacrificing clarity.

Conclusion

Chromosomes do not determine a person’s sexed experience across their entire lifespan. They initiate development but do not continuously regulate adult physiology. Hormones, not chromosomes, are the active agents shaping the living body.

For trans people undergoing medical transition, this means their bodies aren’t “overriding biology” – they are responding to biology, updating their physiological software to reflect their lived reality.

This analogy is scientifically grounded, intuitive, and helps move public understanding closer to what biologists, endocrinologists, and neuroscientists already recognise: human sex is a dynamic biological system, not a static chromosomal label.

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(Classic but still foundational work on sexual differentiation.)
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