5. The Endocrine (Hormone) System

Hormones, metabolism, reproduction and the brain-body connection

Including female and male hormone systems, lifespan changes, and ADHD

Introduction

The endocrine system is the body's chemical communication network. Hormones released into the bloodstream help coordinate growth, metabolism, blood glucose, stress responses, sleep, reproduction, sexual function, bone health, fluid balance, appetite and many aspects of brain function.

Hormones rarely act alone. They operate through feedback loops connecting the brain, pituitary gland and peripheral organs. Levels also change across the day and across the lifespan, which is why endocrine health is dynamic rather than fixed.

1. The major endocrine glands

2. How hormone signalling works

• Release: An endocrine gland releases a hormone into the bloodstream.
• Transport: The hormone circulates throughout the body, but only cells with the appropriate receptor respond.
• Receptor binding: Hormones bind to receptors on the cell surface or inside cells and alter cellular activity.
• Feedback: The brain and endocrine organs monitor the effect and adjust hormone production, often using negative feedback.
• Rhythms: Some hormones vary substantially by time of day, sleep, meals, stress, menstrual phase, pregnancy, age or illness.

3. The hypothalamus and pituitary: the control centre

The hypothalamus receives information about internal and external conditions and communicates with the pituitary. The pituitary then releases hormones that influence other endocrine glands.

Thyroid axis: TRH → TSH → thyroid hormones (T4/T3)

Adrenal stress axis: CRH → ACTH → cortisol

Reproductive axis: GnRH → LH/FSH → ovarian or testicular sex hormones

Growth axis: Growth hormone and IGF-1 regulate growth and tissue metabolism

Prolactin: Supports milk production and is under strong inhibitory control from hypothalamic dopamine

Vasopressin (ADH): Regulates water balance and contributes to blood-pressure control

Oxytocin: Important in labour, milk let-down and several social/behavioural processes

4. Thyroid hormones and metabolism

The thyroid produces mainly thyroxine (T4) and smaller amounts of triiodothyronine (T3). These hormones influence energy use, temperature regulation, cardiovascular function, digestion, muscle function, growth and brain development.

• Hypothyroidism: Too little thyroid hormone can cause tiredness, feeling cold, constipation, dry skin, slowed thinking, low mood and weight gain.
• Hyperthyroidism: Excess thyroid hormone can cause heat intolerance, tremor, anxiety-like symptoms, palpitations, sweating, weight loss and sleep disturbance.
• Important mind-body point: Thyroid disorders can resemble or worsen psychiatric and cognitive symptoms, which is why thyroid testing is often relevant when symptoms change unexpectedly.

1. The adrenal glands and the stress system

The adrenal cortex produces cortisol, aldosterone and adrenal androgens. The adrenal medulla releases adrenaline and noradrenaline during sympathetic activation.

• Cortisol: Helps regulate metabolism, blood pressure, immune activity and the physiological response to stress. It normally follows a circadian rhythm, usually peaking around the early morning.
• Aldosterone: Helps control sodium, potassium, fluid volume and blood pressure.
• Adrenal androgens: Include DHEA and related hormones that contribute to pubic/axillary hair and sex-steroid physiology.
• Popular culture often labels cortisol simply as the 'stress hormone'. That is incomplete: cortisol is essential for normal physiology. Problems arise when cortisol production is pathologically excessive or deficient, as in Cushing syndrome or adrenal insufficiency.

1. Insulin, glucagon and blood glucose

The endocrine pancreas helps keep blood glucose within a workable range. Insulin lowers circulating glucose by helping tissues take up and store nutrients, while glucagon helps raise glucose during fasting.

• Type 1 diabetes results from immune-mediated loss of insulin-producing beta cells.
• Type 2 diabetes involves insulin resistance with progressive difficulty maintaining normal glucose regulation.
• Insulin is also involved in fat and protein metabolism; it is not simply a 'sugar hormone'.
• Sleep, stress, activity, food intake, weight, genetics and medicines can all influence glucose regulation.

1. Calcium, bone and vitamin D

Parathyroid hormone, vitamin D and other signals regulate calcium and phosphate. This system is essential for bone, muscle, nerve and cardiac function.

Bone is hormonally active and constantly remodelled. Oestrogen, testosterone, thyroid hormone, parathyroid hormone, cortisol, vitamin D and growth-related hormones all influence skeletal health.

1. Hormones and sleep

Hormones and circadian rhythms are tightly linked. Melatonin helps signal biological night, cortisol follows a strong daily rhythm, and sleep loss can alter appetite, glucose regulation and stress signalling.

Endocrine disorders can disrupt sleep, while chronic sleep disruption can itself alter metabolic and hormonal regulation.

1. Female endocrine and reproductive hormones

Female reproductive endocrinology is regulated primarily by the hypothalamic-pituitary-ovarian (HPO) axis. GnRH from the hypothalamus stimulates pituitary LH and FSH, which regulate ovarian follicles, ovulation and the production of oestrogens and progesterone.

The main female sex hormones

• Oestrogens: Especially oestradiol during reproductive years. Important for reproductive tissues, bone, vascular biology and multiple brain processes.
• Progesterone: Rises after ovulation and prepares the endometrium for possible pregnancy; it also has central nervous system effects through progesterone and neurosteroid pathways.
• Androgens: Women also produce testosterone and other androgens from the ovaries and adrenal glands. These contribute to libido, muscle, bone and other functions.
• FSH and LH: Pituitary hormones that regulate follicular development, ovulation and ovarian hormone production.
• Prolactin: Supports lactation. Persistently elevated levels outside normal physiological situations can disrupt menstrual cycles and fertility.

The menstrual cycle

Hormone levels are not constant across the menstrual cycle. Oestradiol generally rises during the follicular phase and peaks around ovulation; progesterone becomes prominent after ovulation during the luteal phase. Both fall before menstruation if pregnancy does not occur.

These fluctuations can influence sleep, appetite, energy, mood, cognition, migraine and other symptoms in susceptible individuals. The degree of change varies considerably between people.

Puberty

Puberty activates the reproductive endocrine axis and produces major changes in oestrogen, progesterone and androgen signalling, alongside rapid physical, emotional and neurodevelopmental change.

Pregnancy and postpartum

Pregnancy produces some of the largest endocrine changes in adult life, including major increases in oestrogen and progesterone and changes in thyroid, cortisol, insulin and prolactin physiology. After birth, oestrogen and progesterone fall rapidly while prolactin and oxytocin may remain important during breastfeeding.

Because sleep, mood, cognition and medication needs can also change dramatically during this period, physical and mental health should be considered together.

Perimenopause and menopause

Perimenopause is the transition towards menopause and can involve substantial fluctuation in ovarian hormone production before periods finally stop. Symptoms can include hot flushes, sleep disturbance, mood change, cognitive complaints, vaginal/urinary symptoms and changes in bone and cardiovascular risk.

Menopause is not an endocrine disease, but the fall in ovarian oestrogen has meaningful effects throughout the body. Treatment decisions, including hormone replacement therapy, should be individualised according to symptoms, risk factors and clinical guidance.

Common female endocrine/reproductive conditions

• Polycystic ovary syndrome (PCOS): A common endocrine-metabolic condition involving ovulatory dysfunction and/or androgen excess, often with insulin resistance.
• Premenstrual disorders: Some people experience marked cyclical physical and emotional symptoms; severe mood symptoms may meet criteria for premenstrual dysphoric disorder.
• Endometriosis: Not simply a hormone disorder, but an oestrogen-responsive inflammatory condition that can cause pelvic pain and infertility.
• Premature ovarian insufficiency: Loss of normal ovarian function before age 40, with implications for fertility, bone and cardiovascular health.
• Hyperprolactinaemia: Raised prolactin can disrupt periods, fertility and sexual function and may be caused by medication, pituitary disease or other factors.

1. ADHD and female sex hormones

This is an important emerging area rather than settled science. A 2025 systematic review found that available studies were broadly suggestive of relationships between ADHD symptoms and female sex hormones, particularly around puberty and the menstrual cycle, but the evidence base remained small and methodologically varied.

One leading hypothesis is that changes in oestrogen can influence dopamine and other catecholamine systems involved in attention, motivation, reward and executive functioning. Periods of lower oestrogen may therefore be associated with greater ADHD symptoms for some women, although this is not universal and cannot yet be reduced to a simple hormone formula.

Across the female lifespan

• Puberty: Some girls experience greater executive-function difficulty, emotional dysregulation or functional impairment as reproductive hormones begin fluctuating.
• Menstrual cycle: Some women report worsening attention, organisation, impulsivity or mood in the late luteal/premenstrual phase, when oestrogen and progesterone are changing and then falling.
• Pregnancy: ADHD symptoms, sleep and functioning can change. Medication decisions require individual risk-benefit assessment rather than assuming treatment must always stop or continue.
• Postpartum: Rapid hormonal change, sleep disruption and new cognitive demands can substantially alter functioning. Mood disorders must also be recognised promptly.
• Perimenopause: Increasing hormonal variability may coincide with worsening concentration, memory, sleep and emotional regulation. Current literature increasingly recognises this clinically, but high-quality ADHD-specific treatment trials remain limited.
• Menopause: Lower ovarian oestrogen may affect cognition and wellbeing, but menopause-specific ADHD evidence remains underdeveloped.

1. Male endocrine and reproductive hormones

Male reproductive endocrinology is regulated primarily by the hypothalamic-pituitary-testicular (HPT) axis. GnRH stimulates pituitary LH and FSH. LH supports testicular testosterone production, while FSH contributes to sperm production.

The main male sex hormones

• Testosterone: The principal circulating androgen. Important for sexual development, libido, sperm production, muscle, bone, red-blood-cell production and aspects of mood and energy.
• Dihydrotestosterone (DHT): A potent androgen formed from testosterone in selected tissues and important in prostate, hair and external genital biology.
• Oestradiol: Men also produce oestradiol, largely through conversion of testosterone. It has important roles in bone, sexual function and other tissues.
• LH and FSH: Pituitary hormones controlling testosterone production and spermatogenesis.
• Inhibin B: Produced by Sertoli cells and participates in feedback regulation of FSH and sperm production.

Puberty and adulthood

During male puberty, rising gonadotropins and testosterone drive sexual maturation, voice change, facial/body hair, muscle and bone development and reproductive capacity.

Testosterone levels vary by time of day and can be influenced by age, obesity, sleep, acute illness, medications and other health conditions. One isolated result should therefore be interpreted in clinical context.

Low testosterone

True hypogonadism means inadequate testicular testosterone production and/or impaired reproductive-axis signalling, accompanied by relevant symptoms and appropriately confirmed biochemical findings.

• Reduced libido or erectile function
• Reduced spontaneous erections
• Reduced muscle mass or strength
• Low bone density
• Infertility
• Low energy or mood symptoms in some cases

These symptoms are nonspecific. Poor sleep, depression, obesity, chronic illness, medication effects and relationship factors can produce similar complaints.

Common male endocrine/reproductive conditions

• Primary hypogonadism: The testes cannot produce adequate testosterone despite appropriate pituitary stimulation.
• Secondary hypogonadism: Reduced hypothalamic/pituitary stimulation of the testes.
• Hyperprolactinaemia: Can suppress gonadal hormone signalling and affect libido, fertility and testosterone.
• Thyroid disease: Can influence sexual function, energy, weight and mood.
• Metabolic disease: Obesity, insulin resistance, diabetes and sleep apnoea can interact strongly with testosterone physiology.

1. ADHD and male sex hormones

Compared with research in females, there is much less clinically useful evidence that normal fluctuations in male sex hormones meaningfully alter day-to-day ADHD symptoms or medication response.

Testosterone interacts with brain development, reward and behaviour, but current evidence does not support diagnosing or treating ADHD through testosterone measurement in otherwise healthy males.

Where symptoms such as fatigue, poor concentration, low libido or low mood appear, clinicians should avoid assuming they are simply ADHD or 'low testosterone'. Sleep disorders, depression, medication effects, substance use, metabolic disease and genuine endocrine disorders may all need consideration.

1. Common endocrine conditions

1. Symptoms that can suggest an endocrine problem

• Unexplained weight gain or weight loss
• Persistent fatigue or unusual weakness
• Marked heat or cold intolerance
• Persistent thirst or frequent urination
• Unexplained palpitations or tremor
• Major change in menstrual pattern
• Unexpected breast milk production
• Persistent sexual dysfunction or infertility
• Unexpected changes in body hair or androgenic features
• Loss of height, recurrent fractures or unexplained low bone density
• Significant change in growth or pubertal development
• Persistent unexplained changes in mood or cognition accompanied by physical symptoms

1. How doctors investigate the endocrine system

Endocrine investigation depends heavily on timing and context because many hormones fluctuate during the day, menstrual cycle, illness or after meals.

• Blood tests: May include TSH/T4, glucose/HbA1c, cortisol, prolactin, LH/FSH, testosterone, oestradiol, calcium and other markers depending on the question.
• Urine or saliva tests: Used selectively for specific endocrine questions, particularly some cortisol disorders.
• Dynamic tests: Some hormones need stimulation or suppression testing rather than a single measurement.
• Imaging: Ultrasound, CT or MRI may be used to examine thyroid, adrenal, pituitary, ovarian or testicular structures.
• Bone-density scanning: DEXA can assess bone mineral density where osteoporosis risk is relevant.
• Clinical pattern: Symptoms, medication, menstrual/reproductive history, sleep, weight, timing and family history are often as important as the laboratory value itself.

1. Hormone tests: why context matters

• A laboratory 'normal range' is not the same thing as an ideal value for every clinical question.
• Some hormones vary strongly by time of day.
• Sex hormones can vary by menstrual phase, contraception, pregnancy and menopause.
• Acute illness, calorie restriction, obesity and sleep deprivation can alter endocrine results.
• Medicines can change hormone concentrations or interfere with laboratory assays.
• Abnormal results sometimes need repeat testing before a diagnosis is made.

1. Endocrine disruptors: an emerging public-health issue

Endocrine-disrupting chemicals are substances that can interfere with hormone synthesis, transport, receptors, metabolism or elimination. Research includes chemicals used in plastics, pesticides, industrial products and consumer goods.

This is a legitimate scientific field, but individual risk from a particular everyday exposure is often difficult to quantify. The topic is better approached through evidence-based public-health regulation and sensible exposure reduction than through fear-based 'detox' claims.

1. Mind × Body

Anxiety, depression, ADHD and endocrine disorders can overlap in symptoms such as poor concentration, fatigue, sleep disturbance, appetite change and emotional instability. This is why significant changes should be assessed rather than automatically attributed to an existing psychiatric diagnosis.

1. Protecting endocrine health

• Maintain regular physical activity
• Prioritise sleep and circadian regularity
• Avoid smoking
• Keep alcohol intake low
• Eat a nutritionally adequate, varied diet
• Maintain metabolic health and address diabetes risk
• Avoid unregulated hormone or steroid products
• Take prescribed endocrine medicines consistently
• Seek assessment for persistent hormonal or reproductive symptoms
• Attend appropriate screening and monitoring during menopause, diabetes, thyroid disease or long-term steroid treatment

1. When to seek urgent medical help

The endocrine system at a glance

• ADHD × sex hormones: what we can currently say

Selected contemporary references

Endocrine Society. The Essential Guide to Your Hormones. Overview of major endocrine glands, hormones and functions.

Endocrine Society. Endocrine systems and endocrine-disrupting chemicals reports. Reference information on endocrine axes and hormone physiology.

• Osianlis E, Thomas EHX, Jenkins LM, Gurvich C. ADHD and Sex Hormones in Females: A Systematic Review. Journal of Attention Disorders. 2025;29(9):706-723. Systematic review of ADHD symptoms across female hormonal changes; found suggestive but limited evidence, particularly for puberty and menstrual-cycle effects.
• Kooij JJS et al. Research advances and future directions in female ADHD: the lifelong interplay of hormonal fluctuations with mood, cognition, and disease. Frontiers in Global Women's Health. 2025. Contemporary lifespan review covering puberty, menstrual cycle, pregnancy and perimenopause/menopause, while highlighting major evidence gaps.
• Neurohaven note: This is an educational overview, not a substitute for individual endocrine, reproductive or ADHD assessment. Hormonal symptoms can overlap with neurological and psychiatric symptoms, and significant change deserves appropriate medical evaluation.