What Labs Should Be Checked for Hormone Optimization?

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Article: What Labs Should Be Checked for Hormone Optimization?  |  Category: Hormone  |  Authored by: Brian Lamkin, DO

Optimization Is a Different Question Than Screening

When a patient asks "are my hormones normal?" and when a patient asks "are my hormones optimal?" they are asking two fundamentally different questions that require different lab panels and different interpretation frameworks. Standard screening detects disease: overt hypothyroidism, frank hypogonadism, Addison's disease. Optimization evaluates whether the hormonal system is functioning at the level that supports energy, body composition, cognition, mood, libido, sleep, and longevity. The lab panels are different. The reference ranges are different. The clinical decisions that follow are different. This article describes the complete panel for hormone optimization and the functional ranges that guide those decisions.

The Sex Hormone Panel

The minimum sex hormone panel for optimization includes total testosterone, free testosterone (calculated from total testosterone and SHBG, or by equilibrium dialysis), estradiol, progesterone (drawn on cycle day 19 to 21 in premenopausal women), SHBG, DHEA-S, LH, FSH, and prolactin. Each marker evaluates a different node in the reproductive hormone network, and omitting any one can leave a clinically significant driver unidentified.

Total Testosterone and Free Testosterone

Total testosterone is the most commonly ordered test and the one most frequently misinterpreted^[1]. Standard reference ranges for men extend from approximately 264 to 916 ng/dL. A man with total testosterone of 300 ng/dL is technically "normal" but is at the lower extreme of the population distribution and almost certainly symptomatic. Functional optimal for men is 600 to 900 ng/dL. For women, functional optimal total testosterone is 40 to 70 ng/dL. Free testosterone is even more clinically relevant because it represents the biologically active fraction. A man with total testosterone of 550 but SHBG of 80 may have a free testosterone equivalent to a man with total testosterone of 350. Without free testosterone and SHBG, the total level alone cannot guide optimization.

SHBG: The Gatekeeper

SHBG determines how much of the total testosterone and estradiol is actually available to tissues^[2]. It is produced primarily by the liver and is influenced by multiple systems: insulin resistance lowers SHBG (often dramatically), hypothyroidism lowers SHBG, obesity lowers SHBG, oral estrogen therapy raises SHBG, hyperthyroidism raises SHBG, aging raises SHBG, and liver disease raises SHBG. A patient with a "normal" total testosterone of 500 and an SHBG of 75 has substantially less bioavailable testosterone than a patient with total testosterone of 500 and SHBG of 30. SHBG is the single most under-ordered hormone test in primary care and one of the most clinically decisive in optimization practice.

Estradiol in Men and Women

Estradiol is essential in both sexes. In women, estradiol evaluation varies by clinical context: follicular phase, luteal phase, perimenopausal, or postmenopausal timing determines the expected range and the clinical question being answered. In men, estradiol matters because testosterone converts to estradiol via aromatase, and this conversion increases with visceral adiposity. Elevated estradiol in men produces symptoms that overlap with low testosterone: gynecomastia, reduced libido, mood changes, and fluid retention. Functional optimal estradiol in men is typically 20 to 35 pg/mL. Below 20 is associated with bone loss and joint symptoms. Above 40 is associated with estrogenic symptoms and increased cardiovascular risk. In women, optimal ranges depend on menopausal status and are interpreted alongside progesterone.

Progesterone: The Most Undertested Hormone in Women

Progesterone is frequently omitted from hormone panels and is arguably the most clinically significant hormone in premenopausal and perimenopausal women. Progesterone deficiency (relative to estradiol) produces estrogen dominance: PMS, heavy or irregular periods, breast tenderness, anxiety, insomnia, and weight gain. In premenopausal women, progesterone must be drawn on cycle day 19 to 21 (mid-luteal phase) to assess whether ovulation occurred and whether the corpus luteum produced adequate progesterone. A luteal progesterone below 10 ng/mL suggests anovulation or inadequate luteal function. Functional optimal is 15 to 25 ng/mL in the luteal phase. In perimenopausal and postmenopausal women, progesterone supplementation is evaluated differently but remains essential for sleep, mood, bone health, and breast tissue protection when estrogen is present.

DHEA-S: Adrenal Reserve

DHEA-S is the most abundant circulating steroid hormone and a precursor to both testosterone and estrogen. It is produced primarily by the adrenal glands and declines steadily with age, beginning around age 25 to 30. DHEA-S reflects adrenal steroidogenic capacity and reserve. Low DHEA-S in the context of high cortisol suggests adrenal stress with depletion. Low DHEA-S with low cortisol suggests late-stage adrenal dysfunction. Functional optimal varies by age and sex but generally: 200 to 400 mcg/dL in men aged 30 to 50, 150 to 350 mcg/dL in women aged 30 to 50, with lower (but not absent) expectations in older age groups.

LH, FSH, and Prolactin

LH and FSH distinguish primary from secondary hormone deficiency^[3]. Primary hypogonadism (testicular or ovarian failure) produces elevated LH and FSH as the pituitary attempts to stimulate a failing gland. Secondary hypogonadism (pituitary or hypothalamic dysfunction) produces low or inappropriately normal LH and FSH despite low sex hormones. This distinction fundamentally changes treatment approach. Prolactin is checked because elevation (from pituitary adenoma, medication effect, or hypothyroidism) suppresses GnRH and reduces gonadal function. Unexplained low testosterone or amenorrhea should always prompt prolactin evaluation before initiating hormone therapy.

The Full Thyroid Panel

Thyroid function directly influences sex hormone metabolism. Hypothyroidism reduces SHBG, impairs ovulation, and can reduce testosterone production. Thyroid dysfunction is one of the most common concurrent findings in patients presenting for hormone optimization. The full panel includes TSH, Free T3, Free T4, Reverse T3, and TPO antibodies^[4]. Functional optimal TSH is 0.5 to 2.0 mIU/L (not the standard range extending to 4.5 or 5.0). Free T3 functional optimal is 3.0 to 3.5 pg/mL. Reverse T3 above 15 ng/dL with low Free T3 indicates poor conversion. Optimizing sex hormones without evaluating and treating thyroid dysfunction produces incomplete and unstable results.

Cortisol and Adrenal Evaluation

Chronic cortisol elevation suppresses GnRH (reducing LH, FSH, and downstream sex hormones), interferes with thyroid conversion, and drives insulin resistance. A patient presenting for testosterone optimization who has unaddressed cortisol dysregulation will not respond adequately to testosterone therapy because the cortisol pattern is actively suppressing the axis. Four-point salivary cortisol or DUTCH testing reveals the diurnal pattern. Single-point morning serum cortisol cannot identify flattened, reversed, or late-stage dysfunction patterns that are common in patients with hormone complaints.

The Metabolic Context Markers

Hormones do not operate in a metabolic vacuum. Fasting insulin and HOMA-IR are essential because insulin resistance is one of the most common drivers of hormonal dysfunction: it lowers SHBG, increases aromatase activity, impairs ovulation, and produces the PCOS phenotype. Vitamin D is a steroid hormone precursor and deficiency impairs testosterone production and immune function. RBC magnesium is essential for enzymatic steps in steroid hormone synthesis. Ferritin reflects iron stores that influence thyroid hormone synthesis and energy production. hs-CRP identifies systemic inflammation that drives hormonal disruption. These are not "hormone tests" per se, but without them, hormone optimization is built on an incomplete foundation.

Timing and Methodology

Testosterone in men should be drawn fasting before 10 AM when levels are highest. Progesterone in premenopausal women must be drawn on cycle day 19 to 21 (mid-luteal phase). Estradiol timing depends on clinical question: follicular phase estradiol (day 3 to 5) for baseline ovarian function, luteal phase for ratio interpretation with progesterone. Cortisol requires multi-point testing (4-point salivary or DUTCH), not a single morning serum draw. Free testosterone should be calculated from total testosterone and SHBG or measured by equilibrium dialysis. Analog free testosterone assays are unreliable and should be avoided. Thyroid markers can be drawn any time but should be drawn before taking thyroid medication on the day of testing.

The Lamkin Clinic Optimization Panel

Our standard hormone optimization panel includes: total and free testosterone, estradiol, progesterone (timed), SHBG, DHEA-S, LH, FSH, prolactin, TSH, Free T3, Free T4, Reverse T3, TPO antibodies, 4-point cortisol, fasting insulin, HOMA-IR, vitamin D, RBC magnesium, ferritin, and hs-CRP. This is interpreted as a network, not as individual markers. Patterns reveal the driver: elevated SHBG with low free testosterone is a different clinical problem than low total testosterone with low LH, which is different from normal testosterone with elevated cortisol suppressing the axis. The pattern determines the treatment. The treatment is not always hormone replacement. Often it is addressing the metabolic, thyroid, or adrenal dysfunction that is causing the hormonal disruption.

The Lamkin Clinic, Edmond Oklahoma | lamkinclinic.com

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References and Further Reading

1. [1]Vermeulen A, et al. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab. 1999;84(10):3666-3672.
2. [2]Ding EL, et al. Sex hormone-binding globulin and risk of type 2 diabetes in women and men. N Engl J Med. 2009;361(12):1152-1163.
3. [3]Mulhall JP, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018;200(2):423-432.
4. [4]Garber JR, et al. AACE/ATA guidelines for hypothyroidism in adults. Endocr Pract. 2012;18(6):988-1028.