What is causing a female patient's delayed menstruation, given her history of hyperparathyroidism (high PTH levels), thrombocytosis (high platelet count), and elevated vitamin B12 levels, while taking progesterone 100mg, testosterone 7.5mg, and sermorelin (sermorelin) 20 units, with a recent reaction to glutathione injection?

Delayed Menstruation in Patient on Hormone Therapy

The most likely cause of this patient's 10-day delayed period is the exogenous testosterone (7.5mg) disrupting normal ovarian function and endometrial development, potentially compounded by the recent discontinuation of an unspecified medication and the glutathione reaction triggering systemic stress. 1, 2

Primary Focus: Medication-Induced Menstrual Disruption

The testosterone dose of 7.5mg is the most concerning factor here. Elevated testosterone—even when mostly protein-bound—can inhibit estrogen-mediated endometrial proliferation and prevent adequate endometrial development necessary for menstruation. 2 This has been documented in women with polycystic ovarian syndrome who fail to menstruate after progesterone withdrawal despite normal estrogen levels. 2

Key Mechanism

• Testosterone at this dose likely creates a hyperandrogenic state that blocks normal endometrial response to progesterone 100mg. 2
• The progesterone dose (100mg) is appropriate for inducing withdrawal bleeding in secondary amenorrhea, but requires adequate prior estrogen priming of the endometrium. 3
• If testosterone has prevented estrogen-mediated endometrial thickening, progesterone withdrawal will not trigger menstruation. 2

Secondary Contributing Factors

The Glutathione Reaction and Medication Discontinuation

• The recent adverse reaction to glutathione injection and subsequent medication discontinuation (the unspecified drug stopped in the recent month) represents an acute physiologic stressor. 4
• Stress factors can disrupt the hypothalamic-pituitary-ovarian axis and delay ovulation/menstruation. 4, 5
• The timing correlation—stopping medication and having the reaction just before the delayed period—suggests this contributed to the disruption. 4

Sermorelin (Growth Hormone Releasing Hormone)

• Sermorelin 20 units affects growth hormone secretion but has minimal direct impact on menstrual cyclicity in the absence of other pathology. 5
• However, growth hormone does interact with IGF-1 and metabolic function, which could indirectly affect ovarian function. 1

The Hyperparathyroidism Connection

The elevated PTH levels are particularly relevant because both estradiol and progesterone directly stimulate PTH secretion from parathyroid tissue in a dose-dependent manner. 6

• If this patient has primary hyperparathyroidism, the exogenous progesterone 100mg may be worsening her PTH elevation. 6
• This creates a metabolic environment that could further disrupt normal menstrual cyclicity through calcium dysregulation. 6
• Serum PTH levels and calcium should be carefully monitored in any patient receiving progesterone therapy who has known hyperparathyroidism. 6

The Thrombocytosis and B12 Elevation

The platelet count of 439 (mild thrombocytosis) and elevated B12 are likely incidental findings unrelated to the menstrual delay. 1

• Thrombocytosis at this level does not directly affect ovarian function or menstrual cyclicity. 1
• Elevated B12 can occur with supplementation or certain metabolic conditions but does not cause amenorrhea. 5
• However, these findings warrant investigation for underlying myeloproliferative disorders or other systemic conditions that could indirectly affect overall health. 1

Immediate Diagnostic Approach

Before attributing the delayed period solely to medications, pregnancy must be excluded—this remains the most common cause of menstrual irregularity in reproductive-age women. 4

Essential First-Line Testing

• Urine or serum β-hCG to exclude pregnancy. 4
• Pelvic ultrasound to assess endometrial thickness. 1 If endometrial stripe is <5mm, this confirms inadequate estrogen priming and explains failure to menstruate after progesterone. 2
• Measure LH, FSH, and estradiol (ideally as average of three samples 20 minutes apart on cycle days 3-6 if/when menses resume). 1 An LH/FSH ratio >2 would suggest PCOS, which combined with exogenous testosterone could severely disrupt cycles. 1
• Measure total and free testosterone levels. 1 The 7.5mg dose may be creating supraphysiologic levels that are blocking normal ovarian function. 2

Additional Relevant Testing

• TSH and free T4 to exclude thyroid dysfunction, which commonly causes menstrual irregularity. 1, 5
• Prolactin (morning resting sample) to exclude hyperprolactinemia, which can cause amenorrhea and occurs in 20% of secondary amenorrhea cases. 1, 7
• Repeat PTH and serum calcium given her history and current progesterone use. 6

Management Algorithm

Step 1: Immediate Actions

• Discontinue or significantly reduce testosterone dose. 2 The 7.5mg dose is likely excessive and is the most probable culprit for the menstrual disruption. 2
• Continue progesterone 100mg but recognize it will not induce withdrawal bleeding if endometrium is inadequately primed. 3, 2

Step 2: If Pregnancy Excluded and Endometrium Thin (<5mm)

• This confirms testosterone-induced suppression of endometrial development. 2
• Hold testosterone for at least 4-6 weeks to allow endogenous estrogen to rebuild endometrium. 2
• Then retry progesterone withdrawal (400mg daily for 10 days) to induce menses. 3

Step 3: If No Menses After 4 Months

• This represents secondary amenorrhea requiring endocrinology or gynecology referral. 4, 5
• Do not delay evaluation beyond 4 months—this is abnormal and requires specialist assessment. 4

Step 4: Long-term Hormone Management

• If testosterone is medically necessary, the dose must be titrated to maintain free testosterone in normal female range while monitoring menstrual cyclicity. 1
• Consider switching to transdermal estradiol (50-100 μg patches) plus cyclic oral progesterone (200mg for 12-14 days per month) if she requires hormone replacement. 1 This provides more physiologic hormone delivery and better cycle control. 1
• Avoid combined oral contraceptives in this patient—they will mask the underlying problem and may worsen bone health if she has functional hypothalamic amenorrhea. 1

Critical Pitfalls to Avoid

• Never assume a 10-day delayed period is "normal variation"—cycles >35 days apart are abnormal and warrant evaluation. 4
• Do not continue testosterone at current dose without investigating its impact on menstrual function. 2
• Do not overlook the hyperparathyroidism—progesterone may be stimulating PTH secretion and worsening her metabolic status. 6
• Do not attribute everything to "stress" from the glutathione reaction without ruling out medication-induced causes first. 4, 2