Causes of Elevated LH in Females
Primary Ovarian Insufficiency (POI) / Menopause
Elevated LH in females is most commonly caused by primary ovarian insufficiency or menopause, where loss of ovarian feedback leads to compensatory elevation of both FSH and LH. 1
- FSH >35 IU/L combined with LH >11 IU/L reliably indicates ovarian failure rather than hypothalamic dysfunction or other causes 1
- The LH/FSH ratio in POI/menopause is typically **<1**, distinguishing it from polycystic ovary syndrome where the ratio is often >2 1
- During the menopausal transition, FSH rises more dramatically than LH, with FSH increasing throughout the cycle while LH may remain in the normal range initially 2
- In perimenopausal women (ages 46-56), FSH concentrations are strikingly elevated throughout the cycle while LH remains normal, emphasizing that these gonadotropins are modulated independently at the pituitary level 2
Polycystic Ovary Syndrome (PCOS)
- LH levels in PCOS are variable but often elevated, with an LH/FSH ratio >2 observed in 35-44% of patients 3
- The elevated LH in PCOS declines gradually after ovulation to normal or near-normal range at the end of the luteal phase and early follicular phase, then gradually elevates again with increasing days from menstrual flow 4
- Chronically elevated LH during the follicular phase in PCOS is deleterious to normal reproductive processes, increasing androgen production that diminishes follicular function and reduces early embryo viability 5
- The timing of hormonal analysis is critical for correct diagnosis, as LH levels fluctuate significantly throughout the cycle in PCOS patients 4
Hypothalamic Amenorrhea (Low Energy Availability)
- Low energy availability causes disruptions in LH pulsatility, leading to menstrual dysfunction, but this typically presents with low or normal LH, not elevated LH 6
- This condition is characterized by LH <7 IU/L measured on cycle days 3-6, distinguishing it from causes of elevated LH 3
Pituitary Cross-Reactivity and Hypogonadism
- Unilateral orchiectomy and chemotherapy can cause low testosterone levels in males, which leads to increased pituitary production of LH and hCG, with LH cross-reacting in some hCG assays (detection limit requires <2% cross-reactivity with LH) 6
- In females, hypogonadism from any cause (including marijuana use) can elevate LH through loss of negative feedback 6
Physiologic Variations During Normal Menstrual Cycle
- Mid-cycle LH surge: The preovulatory LH peak represents the highest physiologic elevation, reaching levels that stimulate ovulation 6
- During the late follicular phase, bioactive serum LH can rise 8-fold (to 258 ± 120 mIU/mL) following LHRH stimulation, with significantly increased bio:immuno ratio from 1.7 to 2.5 7
- Postmenopausal women demonstrate a bio:immuno LH ratio of 2-3 (compared to near unity in cycling women), indicating relatively higher biological activity during states of increased gonadotropin biosynthesis 7
Elevated FSH with Variable LH Patterns
- In subfertile young women with consistently elevated basal FSH (reflecting low ovarian reserve), LH may be elevated in all phases of the cycle along with lower inhibin A and B during early follicular phase 8
- Temporary normalization of FSH can occur when inhibin B normalizes in the preceding luteal phase, suggesting a temporary increase in available follicular cohort 8
Clinical Pitfalls to Avoid
- Do not rely on a single LH measurement: In PCOS, LH varies dramatically throughout the cycle; in POI, confirm with repeat testing at least one month apart 1, 4
- Always measure FSH alongside LH: The LH/FSH ratio is critical for differential diagnosis—ratio >2 suggests PCOS, ratio <1 suggests POI/menopause 3, 1
- Check for assay interference: Heterophilic antibodies can cause false-positive results in women, and LH cross-reactivity affects some hCG assays 6
- Consider timing within the cycle: Early follicular phase measurements (cycle days 3-6) provide the most reliable baseline, avoiding the mid-cycle surge 3