Luteinizing Hormone (LH): Role in Reproductive System and Treatment of Related Disorders
Luteinizing hormone (LH) plays a critical role in reproductive function by regulating gonadal steroidogenesis, ovulation, and corpus luteum formation, with disorders of LH secretion requiring targeted treatments based on the specific imbalance.
Physiological Role of LH in Reproduction
Female Reproductive System
- LH is secreted by the anterior pituitary in response to pulsatile gonadotropin-releasing hormone (GnRH) from the hypothalamus 1
- During follicular phase:
- Acts on theca cells through specific receptors to stimulate androgen production
- Androgens are converted to estrogens in granulosa cells via aromatization
- Plays a biphasic role in late follicular phase: positive effect on steroidogenesis but negative effect on cell proliferation 2
- During ovulation:
- LH surge triggers final oocyte maturation and follicular rupture
- Transforms the ruptured follicle into corpus luteum
- During luteal phase:
- Maintains corpus luteum function and progesterone production
- Essential for early pregnancy maintenance until placental function is established 2
Male Reproductive System
- Stimulates Leydig cells in the testes to produce testosterone
- Works synergistically with FSH to maintain spermatogenesis
- Leydig cell dysfunction is characterized by increased LH concentrations combined with low testosterone levels 1
Disorders Related to LH Imbalance
Hypogonadism
- Primary hypogonadism: Characterized by elevated LH/FSH with low sex steroids due to gonadal failure
- Secondary (central) hypogonadism: Low LH/FSH and low sex steroids due to hypothalamic-pituitary dysfunction
- Hypothalamic amenorrhea: Found in 12% of women with temporal lobe epilepsy, characterized by disturbed secretion of pituitary gonadotropins with low LH levels 1
Polycystic Ovary Syndrome (PCOS)
- Common cause of irregular periods affecting 4-6% of women in general population
- Characterized by hypersecretion of LH, elevated LH/FSH ratio >2, and hyperandrogenism
- Pathogenesis involves acceleration of pulsatile GnRH secretion, insulin resistance, and hyperinsulinemia
- Results in ovarian theca stromal cell hyperactivity and hypofunction of FSH-granulosa cell axis 1
Precocious Puberty
- Early activation of the hypothalamic-pituitary-gonadal axis
- Premature pulsatile secretion of GnRH induces release of LH and FSH
- Defined as Tanner stage 2 breast development before age 8 years in girls
- Can occur after cranial irradiation that includes the hypothalamus 1
Diagnostic Evaluation
Laboratory Assessment
- LH measurement: Ideally calculated based on average of three estimations taken 20 minutes apart between days 3-6 of menstrual cycle
- Abnormal findings include:
- LH/FSH ratio >2 (suggestive of PCOS)
- FSH >35 IU/L with LH >11 IU/L (suggestive of ovarian failure)
- LH <7 IU/mL (suggestive of hypothalamic dysfunction) 1
- Additional tests:
- Progesterone (mid-luteal phase): <6 nmol/L indicates anovulation
- Testosterone: >2.5 nmol/L may indicate PCOS or valproate effect
- Pelvic ultrasound to assess ovarian morphology 1
Treatment Approaches for LH-Related Disorders
Hypogonadism with Desired Fertility
- For men with hypogonadism who desire fertility: Clomiphene citrate (a selective estrogen receptor modulator) is preferred over testosterone replacement therapy
- Blocks estrogen's negative feedback on hypothalamus and pituitary
- Stimulates endogenous LH and FSH secretion
- Increases testosterone production without suppressing spermatogenesis 3
Polycystic Ovary Syndrome
- Treatment focuses on addressing specific symptoms and fertility concerns
- For anovulation and infertility:
- Lifestyle modifications (weight reduction if overweight)
- Ovulation induction agents
- Insulin-sensitizing medications if insulin resistance present 1
Precocious Puberty
- GnRH analogs are the treatment of choice
- Work through continuous stimulation to desensitize gonadotrophs
- Reduce LH release, thus halting ovarian stimulation
- Preserve final adult height, delay menarche, and optimize development of secondary sex characteristics
- Treatment usually continues until the normal age of puberty 1
Cancer Treatment-Related Hypogonadism
- Risk factors for ovarian failure include:
- Alkylating agent-based chemotherapy (60% risk vs. 3-6% with non-alkylating agents)
- Radiation therapy to ovaries (doses as low as 5 Gy can affect function)
- Age at treatment (higher risk in older patients) 1
- Management:
- Hormone replacement therapy for symptom management
- Fertility preservation options before gonadotoxic therapy
- Regular monitoring of gonadal function 1
Clinical Considerations and Pitfalls
- LH levels fluctuate throughout the menstrual cycle, requiring appropriate timing of measurement
- Results from different laboratories may not be comparable due to variations in assay methods 4
- Regular menstrual cycles while on oral contraceptives may mask premature ovarian failure 1
- Exogenous LH administration for assisted reproduction requires careful dosing:
- Recent research suggests LH may have extragonadal effects on endometrial stem cells that could impact fertility treatment outcomes 6
By understanding the complex role of LH in reproductive physiology and the appropriate management of disorders related to LH imbalance, clinicians can optimize treatment outcomes for patients with reproductive health concerns.