The hypothalamic-hypophyseal-gonadal axis can be evaluated by administering drugs and hormones known to affect specific hormonal interactions. These include clomiphene, GnRH, hCG, and progesterone.

Clomiphene, a drug used to treat infertility, prevents the hypothalamus from recognizing normally inhibitory levels of estrogen and testosterone. Consequently, the hypothalamus continues to secrete GnRH, which, in turn, continues to stimulate the adenohypophysis to secrete FSH and LH. After 5 days of clomiphene, both FSH and LH levels rise, usually 50 to 100 percent above baseline levels. In anovulatory women whose ovaries are normal, clomiphene often enhances FSH and LH levels so that ovulation is induced. If FSH and LH levels do not rise with clomiphene administration, either hypothalamic or hypophyseal dysfunction is indicated. The source of the dysfunction may be identified by administering purified GnRH. If FSH and LH levels rise, the pituitary gland is normal but hypothalamic function is impaired. FSH and LH levels that do not rise indicate hypophyseal dysfunction.

Human chorionic gonadotropin (hCG), a placental hormone with effects similar to those of LH, is used to evaluate testicular activity in men with low testosterone levels. Elevated testosterone levels after hCG administration indicate that testicular function is normal but that hypothalamic-pituitary activity is impaired. Failure of testosterone levels to rise suggests primary testicular dysfunction.

Progesterone, a hormone secreted by the ovary, is used to evaluate amenorrhea. In the normal menstrual cycle, the progesterone surge that follows ovulation inhibits GnRH secretion, and hormonal levels decline. Menstrual bleeding, also called withdrawal bleeding, occurs when the estrogen-stimulated endometrium experiences a drop in hormonal stimulation. This normal situation can be simulated by administering oral or IM progesterone to amenorrheic women already exposed to adequate estrogen levels. If menstrual bleeding occurs, the underlying cause of the amenorrhea is failure to ovulate. Lack of bleeding in response to progesterone administration indicates (1) inadequate estrogen production, resulting from either primary ovarian failure or inadequate pituitary secretion of FSH; (2) hypothalamic dysfunction with defective GnRH secretion; (3) impaired hypophyseal response to GnRH; or (4) abnormal uterine response to hormonal stimulation. These possibilities can be distinguished by administering estrogen to stimulate the endometrium and then repeating the progesterone challenge. If bleeding occurs, then either ovarian failure or inadequately responsive hypothalamic-hypophyseal activity is the underlying cause of the amenorrhea. Measuring FSH, LH, and estrogen levels helps further to diagnose the problem.⁴³

Note: Results should be evaluated in relation to other tests of gonadal function.

• In menstruating women, values vary in relation to the phase of the menstrual cycle.
• Values are higher in postmenopausal women.
• Administration of the drug clomiphene may result in elevated FSH levels.
• Therapy with estrogens, progesterone, and phenothiazines may result in decreased FSH levels.⁴⁴

• Evaluation of ambiguous sexual differentiation in infants
• Evaluation of early sexual development in girls under age 9 years or boys under age 10 years, with precocious puberty associated with elevated levels
• Evaluation of failure of sexual maturation in adolescence
• Evaluation of sexual dysfunction or changes in secondary sexual characteristics in men and women:
  • Elevated levels are associated with ovarian or testicular failure, with polycystic ovary disease, after viral orchitis, and with Turner's syndrome in women and Klinefelter's syndrome in men.
  • Decreased levels may be seen with neoplasms of the testes, ovaries, and adrenal glands, resulting in excessive production of sex hormones.
• Suspected pituitary or hypothalamic dysfunction:
  • Elevated levels may be seen in pituitary tumors.
  • Decreased levels are associated with hypothalamic lesions and panhypopituitarism.
• Suspected early acromegaly as indicated by elevated levels
• Suspected disorders associated with decreased FSH levels, such as anorexia nervosa and renal disease

Nursing Care Before the Procedure

Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I).

• It is recommended that drugs known to alter FSH levels be withheld for 12 to 24 hours before the test, although this practice should be confirmed with the person ordering the study.
• In women, the phase of the menstrual cycle should be ascertained, if possible.

A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported to the laboratory immediately.

Nursing Care After the Procedure

Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample.

• Resume any medications withheld before the test.
• Complications and precautions: Note levels in relation to 24-hour urinary FSH and LH results. Prepare client for serial samples for testing.