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HypO-gonadism

Hypogonadism refers to the impaired production of reproductive hormones by the testes in men and the ovaries in women, which arises from deficient hypothalamic signaling. This includes too little release of gonadotropin-releasing hormone (GnRH), which is the brain’s starter signal that tells the pituitary to release signalling hormones LH and FSH. 
 
In women Luteinising hormone (LH) and follicle-stimulating hormone (FSH) work together across the menstrual cycle. FSH supports ovarian follicles to grow, and supports the increase in aromatase, which increases oestrogen. Mid-cycle LH surges are an essential trigger for ovulation, and ovulation supports the corpus luteum, which makes progesterone to stabilise the uterine lining. Therefore if LH/FSH signalling is too low or poorly pulsed, follicles do not mature properly, ovulation may not occur, and luteal progesterone can be insufficient, creating an array of menstrual disorders.
 
In men, LH stimulates Leydig cells in the testes to produce testosterone. FSH acts on Sertoli cells to support spermatogenesis, including making androgen-binding protein to keep testosterone levels high. When LH and FSH are low, testicular testosterone falls and sperm production declines, leading to low testosterone and the manifestation of this including low libido, erectile issues, and reduced fertility.
 
The biochemical hallmark of central hypogonadism is low sex steroids, estradiol in women and testosterone in men, with LH and FSH that are low. Alternatively it can be diagnosed with Estradiol and Testosterone low, but with LH and FSH inappropriately normal, meaning there has been failure to mount the compensatory rise in signalling, as it should in response to low hormone status. 
 
Women
 
In women signalling hormones and estradiol fluctuate throughout the cycle. The most appropriate time to measure LH, FSH and Estradiol is on ovulation. Ovulation is typically mid cycle, so for a standard 28 day cycle, this would usually occur 14 days after the first day of bleeding. 
 
If you are not tracking your cycle and unsure of which day you ovulate, we advise purchasing a urinary ovulation test from your local pharmacy, which will indicate the day of ovulation, and the best day for the blood to be withdrawn.  
 
Healthy Midcycle Guidelines for Women: 
 

  • LH: 7.6 - 89 IU/L 

  • FSH: 2.6 - 17 IU/L 

  • Oestradiol (E2): 151 - 1461 pmol/L

 
Note: If results are within close proximity to the lower end, or are under these ranges, central hypogonadism is indicated. Similarly if Oestradoil is low, and LH is not elevated, central hypogonadism is indicated. 
 
Guidelines for Absent Menstruation : 
 
In circumstances of an absent menstrual cycle comparing against the lower end of reference ranges is advised, this includes
 

  • LH: 0.6 - 14.0 IU/L

  • FSH: 1.4 - 5.5 IU/L

  • Oestradiol (E2): 45 - 854 pmol/L

 
Note as above. 
 
Healthy Guidelines for Men: 
 

  • LH: 0.6 - 12.1 IU/L 

  • Total testosterone:
    <49 years old: 8.3 - 30.2 nmol/L
    >49 years old: 7.7 - 24.8 nmol/L 

 
If results are within close proximity to the lower end, or are under these ranges, central hypogonadism is indicated. Similarly if Testosterone is low, and LH is not elevated, central hypogonadism is indicated. 
 
[12][13][14][15]
 
Restoring signalling can re-establish ovulation and increase Oestradiol in women, and in men it can increase Testosterone and spermatogenesis. Natural remedies are available that stimulate the brain–pituitary axis, and raise the signalling hormones LH and FSH, which is vital for reproductive function and capacity and preventing the long-term complications associated with chronic hypogonadism.

signs & symptoms - female

Menstrual Absence - Amenorrhea

 

Amenorrhea, or the absence of menstruation for three months or more, is the main sign of Functional Hypothalamic Amenorrhea (FHA), which is a form of Central Hypogonadism, characterized by reduced reproductive hormone signaling, leading to a temporary shutdown of the menstrual cycle.

 

Mechanistically, insufficient LH and FSH secretion leads to both low estrogen levels and the prevention of egg follicle maturation, both of which reduce the induction of ovulation. Without ovulation, no corpus luteum is formed, so there is no progesterone rise. The combined lack of estrogen-driven proliferation and progesterone-driven shedding leaves the endometrium too thin to menstruate, resulting in absent bleeding. [1]

 

Oligomenorrhea 

 

Oligomenorrhea is defined as menstrual cycles occurring at intervals greater than 35 - 45 days, and can reflect a milder degree of central hypogonadism compared to complete loss of the menstrual cycle. Here, partial hormone signalling is maintained, but follicular development and recruitment is impaired, leading to prolonged and irregular cycles. [1]

 

Estrogen + Progesterone Deficiency

 

  • Light menstrual bleeding

  • PMS symptoms

 

Furthermore, since central hypogonadism results in reduced FSH and LH secretion, ovarian stimulation is therefore inadequate and this also leads to both insufficient estradiol and progesterone production. The insufficient estrogen causes incomplete endometrial proliferation during the follicular phase, and as a result, when menstruation does occur, the endometrial lining is thin, producing lighter or shorter bleeding episodes rather than a full, normal flow. The insufficient progesterone contributes to symptoms of PMS such as irritability, hypersensitivity and low mood. [1]

signs & symptoms - male

Clinical manifestations of low testosterone occur along a spectrum. The examples below represent features of markedly low testosterone, with symptom severity diminishing along the continuum toward normal testosterone function.

 

Erectile + Sexual Dysfunction

 

  • Inability to achieve erection in more than 75% of attempts

  • Erection is achieved but lost within 1 - 2 minutes before penetration

  • Erection only possible with manual stimulation and not sustained

  • No nocturnal or morning erections 

  • Diminished Penile Sensations

  • Difficulty attaining orgasm

 

Male hypogonadism, defined by insufficient testosterone production, directly impairs sexual function by disrupting testosterone-dependent physiological pathways. Testosterone is essential for nitric oxide release and vascular responsiveness within penile tissue, both of which enable adequate blood flow and rigidity during erection. Deficiency in this hormone reduces penile sensitivity and impairs the neurovascular mechanisms required for erection, resulting in erectile dysfunction and difficulties achieving orgasm. Collectively, these manifestations reflect the broader sexual dysfunction associated with androgen deficiency, where vascular, neurological, and sensory integrity are all compromised. [38][45][46]

 

Low Libido

 

Low testosterone also profoundly affects libido by diminishing androgen-dependent activity within the hypothalamic and limbic centers of the brain that govern sexual motivation and desire. This reduced central drive for sexual activity often precedes or accompanies erectile difficulties and is a hallmark feature of hypogonadism. In addition, chronic testosterone deficiency can blunt dopaminergic signaling and overall arousal response, further compounding loss of interest in sexual activity and reducing spontaneous sexual thoughts or behaviors. [38][46]

 

Infertility

 

  • Low ejaculation volume

  • Poor Sperm Quality 

 

Low Testosterone fails to adequately activate Sertoli and Leydig cell function within the testes, leading to decreased sperm maturation and overall sperm count. This results in a reduced ejaculation volume and compromised semen quality, both of which contribute to a higher probability of infertility. [38]

 

Altered Physique and Energy

 

  • Poor Stamina 

  • Decreased muscle mass, despite physical efforts

  • Localised Abdominal Weight

  • Decreased shaving frequency or body hair

 

Hypogonadism and low testosterone correlate strongly with reduced energy and vitality because testosterone is not only a reproductive hormone but also a key regulator of metabolism, muscle integrity, and neurological function. Adequate testosterone supports mitochondrial efficiency and energy production, preserves lean muscle mass, and promotes red blood cell synthesis, all of which contribute to physical stamina. Low levels impair these processes, leading to fatigue, muscle weakness, and anemia. [38][46]

 

Personality Traits 

 

  • Risk Avoidant

  • Low Confidence 

  • Not Competitive

  • Not Assertive in Decision Making

  • Low Motivation and Drive

  • Prone to Irritability or Sadness 


Research has demonstrated men with adequate or higher testosterone levels typically exhibit greater dominance, confidence, assertiveness, adaptive risk-taking, emotional steadiness, and the capacity for decisive goal orientated action, which are traits underpinned by androgenic modulation of the dopaminergic and limbic circuitry involved in motivation, social behavior, and executive control. 

 

These attributes contrast with the low testosterone presentation, where testosterone deficiency reduces androgenic involvement of dopamine, which in turn corresponds to heightened caution and risk avoidance, diminished initiative, lack of competitiveness and motivation, as well as emotional volatility or low mood. [38][46]

References

 

[1].https://academic.oup.com/jcem/article/102/5/1413/3077281

[2].https://academic.oup.com/jcem/article/102/5/1413/3077281

[3].https://europepmc.org/article/pmc/6785957

[4].https://academic.oup.com/jcem/article/102/5/1413/3077281

[5].https://bmjopen.bmj.com/content/bmjopen/3/8/e003127.full.pdf

[6].https://www.sciencedirect.com/science/article/abs/pii/S0303720706002991

[7].https://www.endotext.org/wp-content/uploads/pdfs/prolactinoma-management.pdf

[8].https://academic.oup.com/jcem/article/101/11/3888/2764912

[9].https://www.nature.com/articles/s41398-022-02027-4.pdf

[10].https://academic.oup.com/jcem/article/96/2/273/2709487

[11].https://www.mdpi.com/2072-6643/14/16/3438

[12].https://www.thermh.org.au/health-professionals/pathology-handbook/luteinizing-hormone

[13].https://www.thermh.org.au/health-professionals/pathology-handbook/follicle-stimulating-hormone

[14].https://www.thermh.org.au/health-professionals/pathology-handbook/oestradiol

[15].https://www.thermh.org.au/health-professionals/pathology-handbook/testosterone-total

[16].https://pubmed.ncbi.nlm.nih.gov/12876296/

[17].https://www.sciencedirect.com/science/article/abs/pii/S0044848618326048

[18].https://pmc.ncbi.nlm.nih.gov/articles/PMC8955126/

[19].https://journals.lww.com/apjr/fulltext/2017/06040/effects_of_dietary_vitamin_e_on_male_reproductive.1.aspx

[20].https://vetdergikafkas.org/uploads/pdf/pdf_KVFD_L_3160.pdf

[21].https://pmc.ncbi.nlm.nih.gov/articles/PMC7468694/

[22].https://pubmed.ncbi.nlm.nih.gov/20446777/

[23].https://www.sciencedirect.com/science/article/abs/pii/S0022316623276944

[24].https://onlinelibrary.wiley.com/doi/abs/10.1002/food.19890331007

[25].https://onlinelibrary.wiley.com/doi/10.1111/and.12482

[26].https://pubmed.ncbi.nlm.nih.gov/20078516/

[27].https://pubmed.ncbi.nlm.nih.gov/16698205/

[28].https://www.researchgate.net/publication/391241517

[29].https://ovarianresearch.biomedcentral.com/articles/10.1186/s13048-022-00945-x

[30].https://khu.elsevierpure.com/en/publications/modulating-effects-of-korean-ginseng-saponins-on-ovarian-function-2

[31] https://pmc.ncbi.nlm.nih.gov/articles/PMC10042648/

[32] https://pmc.ncbi.nlm.nih.gov/articles/PMC3861174/

[33].https://www.sciencedirect.com/science/article/abs/pii/S0944711321000040

[34].https://www.researchgate.net/publication/260150404

[35].https://bmccomplementmedtherapies.biomedcentral.com/articles/10.1186/1472-6882-14-511

[36] https://www.mdpi.com/2072-6643/17/7/1275

[37].https://www.racgp.org.au/afp/2014/may/male-androgen-disorders

[38] https://pmc.ncbi.nlm.nih.gov/articles/PMC3255409/

[39] https://pubmed.ncbi.nlm.nih.gov/32657051/

[40].https://juniperpublishers.com/jetr/pdf/JETR.MS.ID.555710.pdf

[41].https://pdfs.semanticscholar.org/53b8/124401702da7a880ed9314a75c7aeb35f628.pdf

[42].https://pmc.ncbi.nlm.nih.gov/articles/PMC9232848/

[43] https://pmc.ncbi.nlm.nih.gov/articles/PMC7654971/

[44] https://pmc.ncbi.nlm.nih.gov/articles/PMC7654971/
[45].https://accessmedicine.mhmedical.com/content.aspx?bookId=2950&sectionId=248296753
[46] https://pmc.ncbi.nlm.nih.gov/articles/PMC4046605/

cause - female + MALE

Chronic Stress + Inflammation [Hypercortisolism]

 

Chronic Stress + Inflammation are linked to the following conditions: 

 

  • SNS Hyperactivity 

  • Candidiasis

  • Mast Cell Activation

  • Tregs Dysfunction

  • MSK Inflammation

  • Hepatic Insufficiency

  • Herpes + Epstein Barr Virus

 

These states lead to sustained elevations in cortisol, which directly suppresses hypothalamic GnRH secretion. Cortisol alters the activity of kisspeptin and other stimulatory inputs to GnRH neurons, reducing pulsatility. This blunting of GnRH output decreases LH pulse frequency and, to a lesser extent, FSH, leading to insufficient testicular and ovarian stimulation and subsequent declines in reproductive hormone production. [42]

 

This represents an adaptive mechanism by which the body prioritizes survival over reproduction in the face of chronic stress both psychological and physiological. 

 

Hypothyroidism

 

Hypothyroidism disrupts the hypothalamic–pituitary–gonadal axis primarily through elevated thyrotropin-releasing hormone (TRH), which increases prolactin and suppresses gonadotropin-releasing hormone (GnRH). Reduced GnRH output leads to decreased luteinizing hormone (LH) and follicle-stimulating hormone (FSH), impairing follicular development and ovulation, which can cause impaired hormone production [40][41]

 

High Prolactin [ Dopamine Deficiency ]  

 

High Prolactin is induced most frequently by states of dopamine deficiency, since dopamine normally restrains prolactin secretion. The resulting elevated prolactin then  leads to central hypogonadism through suppression of gonadotropin-releasing hormone (GnRH) from the hypothalamus, which thereby decreases LH and FSH signalling for the production of reproductive hormones. [10][37]

 

Functional Hypothalamic Suppression

 

  • Fasting 

  • Nutritional deficiency

  • Excessive exercise

  • Low energy availability

 

Functional Hypothalamic Suppression is a reversible GnRH-pulsatility disorder precipitated by insufficient energy availability from the result of reduced food intake and/or high energy expenditure physical exercise and typically compounded by psychological stress. In these states low levels of leptin and insulin blunts GnRH pulses, decreasing LH and FSH signalling for the production of reproductive hormones. [4]

 

Obesity - Leptin Resistance

 

Obesity is strongly associated with elevated circulating leptin levels, since leptin is secreted in fat mass. This chronic secretion of leptin leads to leptin resistance, where the hypothalamus becomes less responsive to leptin’s normal stimulatory role in reproductive signaling. 

 

In relation to reproduction, leptin acts upstream of the hypothalamic–pituitary–gonadal (HPG) axis by stimulating kisspeptin neurons, which in turn activate GnRH drive. Therefore leptin resistance blunts this pathway, suppressing kisspeptin activity and GnRH pulsatility, which diminishes the downstream secretion of LH and FSH, impairing reproductive hormone production. [3][44]

 

Medications

 

  • Glucocorticoids

  • Opioids 

  • Dopamine-blocking antipsychotics

 

The following medications suppress GnRH activity, and thereby blunt LH + FSH secretion. [6][9]

 

Pituitary or hypothalamic structural disease

 

Growths in the brain near the pituitary gland or hypothalamus, such as prolactinomas or other pituitary tumors can cause central hypogonadism. These growths may press on the pituitary stalk or damage the gland, disrupting normal hormone signals needed for reproduction. In the case of prolactin-secreting tumors, high prolactin further suppresses GnRH release, worsening the hormone imbalance. [7]

 

People affected may notice reproductive or sexual problems, and sometimes symptoms related to the tumor itself, such as headaches or loss of side vision. Doctors usually check for this with pituitary MRI scans. [37]

 

Trauma or Surgery

 

Traumatic brain injury and cranial radiotherapy can damage hypothalamic or pituitary tissue, resulting in isolated or combined pituitary hormone deficits, including LH/FSH deficiency. These presentations may be delayed and require periodic reassessment of pituitary axes. [8]

 

Chronic kidney disease 

 

Kidney Disease disrupts the HPG axis through uremic toxins, inflammation and altered gonadal steroid metabolism, producing low testosterone with low–normal gonadotropins in many men and menstrual disturbance in women. [11]

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