Can a severe concussion from a fall disrupt the hypothalamic‑pituitary‑ovarian axis and worsen perimenopausal symptoms in a woman in her mid‑40s to early‑50s?

Can a Severe Concussion Worsen Perimenopausal Symptoms?

Yes, a severe concussion can disrupt the hypothalamic-pituitary-ovarian axis and potentially worsen perimenopausal symptoms, though the evidence is limited and the mechanism remains incompletely understood.

Evidence for Neuroendocrine Disruption After Concussion

Pituitary Dysfunction Following Mild Traumatic Brain Injury

• Approximately 4.6% of female athletes develop hypopituitarism after mild traumatic brain injury (mTBI), with central hypothyroidism occurring in 3.1% and growth hormone deficiency in 1.5%. 1

• An additional 7.6% of female athletes develop hyperprolactinemia after mTBI, with 3.1% diagnosed with prolactinoma. Hyperprolactinemia in the absence of prolactinoma may represent direct hypothalamic or pituitary injury from the concussion. 1

• Overall, 12.2% of female athletes with a history of mTBI had some form of pituitary dysfunction requiring medical treatment in 9.9% of cases. 1

Hormonal Changes After Concussion

• Female athletes with concussion demonstrate elevated progesterone levels across all post-injury visits compared to controls, with a mean difference of 0.26 ln ng/mL. 2

• Estradiol levels are significantly elevated at 24 hours post-injury, at initiation of return-to-play protocol, and 7 days after unrestricted return-to-play compared to pre-injury baseline. 2

• Concussed participants show reduced variability in estradiol levels over 7-28 days compared to controls, suggesting disrupted normal hormonal cycling. 2

• Acutely after concussion, higher estradiol levels are positively associated with greater psychological symptom severity on the Brief Symptom Inventory Global Severity Index. 2

Perimenopausal Hypothalamic-Pituitary Changes

Baseline HPO Axis Dysfunction in Perimenopause

• The hypothalamic-pituitary-ovarian axis undergoes complicated but coordinated changes during the menopausal transition, with both reproductive and general health consequences. 3

• Older reproductive-age women demonstrate hypothalamic-pituitary insensitivity to estrogen, with failure of both positive feedback (no LH surge despite adequate estrogen peaks) and negative feedback mechanisms. 4

• Women with anovulatory cycles and absent estrogen-positive feedback on LH secretion experience more menopausal symptoms, particularly hot flashes, than women with preserved feedback mechanisms. 4

Clinical Implications and Management

Assessment Priorities

• Screen for thyroid dysfunction (TSH, free T4), growth hormone deficiency (IGF-1), hyperprolactinemia (prolactin), and gonadal function (FSH, LH, estradiol, progesterone) in women with persistent symptoms after concussion. 5, 1

• FSH is not a reliable marker of menopausal status in women with prior head trauma, similar to its unreliability after chemotherapy or pelvic radiation. 5

• Serial estradiol levels can help determine return of normal ovarian function in women who became amenorrheic after injury and later develop bleeding. 5

Symptom Management

• For vasomotor symptoms (hot flashes, night sweats), initiate nonhormonal pharmacologic treatment as first-line therapy: gabapentin 900 mg at bedtime reduces hot flash severity by 46% versus 15% with placebo. 6

• Venlafaxine 37.5-75 mg daily reduces hot flash scores by 37-61% and is preferred when rapid onset is prioritized or when gabapentin is ineffective. 6

• For mood disturbances, irritability, and emotional lability, consider SSRIs/SNRIs after ruling out thyroid disease and other medical causes. 7

• Address sleep disturbance with gabapentin at bedtime, which simultaneously treats both hot flashes and sleep disruption. 6

Important Caveats

• The majority of concussion-related symptoms resolve within one week of injury, so persistent symptoms beyond this timeframe warrant endocrinological evaluation. 5

• Hormonal contraceptive use does not influence concussion recovery trajectory, symptoms, or cognitive function, suggesting that artificial hormonal stabilization does not protect against post-concussive sequelae. 8

• Hyperprolactinemia without prolactinoma may represent direct pituitary or hypothalamic injury and requires endocrinological follow-up rather than dismissal as a transient finding. 1

When to Refer to Endocrinology

• Refer for persistent symptoms beyond 2-4 weeks post-concussion, abnormal screening hormone values on repeat testing, or symptoms significantly impairing daily function. 5, 7

• Complex cases with multiple hormonal abnormalities or comorbid conditions require specialist management. 7