How is LH and FSH measured?
Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are measured in research and clinical settings using immunoassays, typically in serum or plasma. This article outlines the methods and highlights recent stu
Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are measured using immunoassays, most commonly in serum or plasma samples. These glycoprotein hormones are secreted by the anterior pituitary and are key regulators of gonadal function. In research contexts, measurement is performed to assess the hypothalamic-pituitary-gonadal (HPG) axis, diagnose deficiencies, or monitor treatment effects. The most widely used methods are enzyme-linked immunosorbent assay (ELISA), chemiluminescent immunoassay (CLIA), and radioimmunoassay (RIA), each with varying sensitivity and specificity. Measurement of LH and FSH is also integral to clinical trials evaluating therapies for conditions such as hypogonadism and infertility.
LH and FSH belong to the glycoprotein hormone family, which also includes thyroid-stimulating hormone (TSH) and human chorionic gonadotropin (hCG). They are heterodimers composed of a common alpha subunit and a hormone-specific beta subunit. The beta subunit of LH (LHB) and FSH (FSHB) confers biological specificity. Molecular weights are approximately 28-30 kDa for LH and 30-34 kDa for FSH, though glycosylation varies. The genes encoding these subunits are located on chromosomes 19 (LHB) and 11 (FSHB). Measurement relies on antibodies that recognize epitopes on the intact heterodimer or the beta subunit. The HPG axis, involving gonadotropin-releasing hormone (GnRH) from the hypothalamus, regulates their pulsatile release [3].
Research Studies
Follitropin alfa/lutropin alfa and LH/FSH deficiency in Japanese participants undergoing ART
A clinical trial (HINATA) assessed the efficacy and safety of follitropin alfa/lutropin alfa versus human menopausal gonadotropin (hMG) in Japanese participants with LH and FSH deficiency undergoing assisted reproductive technology (ART) [1]. The study measured outcomes related to ovarian stimulation and pregnancy. The study duration was approximately 5.5 months for nonpregnant participants and 13 months for those with confirmed pregnancy in Part A [1]. This trial demonstrates the clinical utility of measuring LH and FSH to diagnose deficiency and monitor response to gonadotropin therapy.
Clomiphene or enclomiphene citrate and gonadotropin levels in male hypogonadism
A systematic review and meta-analysis of randomized controlled trials evaluated selective estrogen receptor modulators (SERMs), specifically clomiphene and enclomiphene, in men with functional hypogonadism [2]. The primary endpoints included total testosterone (TT), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). The analysis compared SERMs with placebo, testosterone gel, or human chorionic gonadotropin (hCG). Weighted mean differences (MDs) and risk ratios (RRs) were calculated for continuous and binary endpoints [2]. This study highlights the importance of measuring LH and FSH to assess treatment effects on the HPG axis.
GLP-1 agonist and neuro-reproductive function in obese adolescent females with PCOS
A clinical trial is investigating the effects of a glucagon-like peptide-1 (GLP-1) agonist on neuro-reproductive function in obese adolescent females with polycystic ovary syndrome (PCOS) [3]. The study notes that normal puberty onset and progression depend on the HPG axis, which is affected by whole-body metabolism. Gonadotropin-releasing hormone (GnRH) and gonadotropins, LH and FSH, are released in a pulsatile manner for appropriate sex steroid production and gonadal function. Proper pulsatility in the GnRH system is disrupted by significant changes in energy balance such as in obesity [3]. This trial measures LH and FSH to evaluate the impact of metabolic intervention on reproductive neuroendocrine function.
Measurement methods and considerations
Immunoassays for LH and FSH are typically performed on serum or plasma, though urine and saliva have been used in research settings. The choice of assay depends on required sensitivity, specificity, and available instrumentation. For research purposes, it is essential to use validated assays with established reference ranges for the population under study. Factors such as pulsatility, circadian rhythm, and sample handling can affect results. In clinical trials, central laboratory measurements are often employed to minimize variability.
| Assay Type | Typical Sensitivity | Common Use |
|---|---|---|
| ELISA | 0.1-1 IU/L | Research, small clinics |
| CLIA | 0.01-0.1 IU/L | Clinical diagnostics |
| RIA | 0.5-2 IU/L | Specialized research |
Interpretation of LH and FSH levels
In research, LH and FSH levels are interpreted in the context of the HPG axis. Elevated levels may indicate primary gonadal failure, while low levels suggest hypothalamic or pituitary dysfunction. In the HINATA trial, participants had LH and FSH deficiency, which was treated with exogenous gonadotropins [1]. In the SERM meta-analysis, changes in LH and FSH were used to assess the effect of clomiphene and enclomiphene on the HPG axis [2]. In the PCOS trial, LH and FSH pulsatility is a key outcome [3].
Challenges in measurement
Measurement of LH and FSH can be challenging due to their pulsatile secretion, short half-lives, and structural heterogeneity. Immunoassays may cross-react with other glycoprotein hormones, particularly hCG, which shares a similar structure. Additionally, different assays may yield different results due to epitope specificity and standardization. For research, it is crucial to use the same assay throughout a study and to follow manufacturer instructions.
Future directions
Advances in assay technology, such as mass spectrometry and automated immunoassays, continue to improve the sensitivity and specificity of LH and FSH measurement. These methods are being applied in research to better understand the HPG axis in various populations, including those with obesity, PCOS, and hypogonadism [2][3].
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Sources
- [1] A Study to Compare the Efficacy and Safety of Follitropin Alfa/Lutropin Alfa Versus hMG in Japanese Participants With LH and FSH Deficiency Undergoing ART (HINATA)
- [2] Clomiphene or enclomiphene citrate for the treatment of male hypogonadism: a systematic review and meta-analysis of randomized controlled trials.
- [3] Effects of Glucagon-like Peptide-1 (GLP-1) Agonist in Neuro-reproductive Function in Obese Adolescent Females With Polycystic Ovary Syndrome (PCOS)