Since regular menstruation depends upon normal function of the entire physiologic axis extending from the hypothalamus and pituitary gland to the ovary and the uterine lining, it is not surprising that menstrual disorders are among the most common presenting complaints of endocrine disease in women. Correct diagnosis depends upon proper evaluation of each component of the axis, and nonendocrine factors must also be considered. If menstruation is defined as shedding of endometrium which has been stimulated by estrogen or by estrogen and progesterone which are subsequently withdrawn, it is obvious that amenorrhea can occur either when hormones are deficient or lacking (the hypohormonal or ahormonal type) or when these hormones, though present in adequate amounts, are never withdrawn (the continuous hormonal type).
Primary amenorrhea implies that mentruation has never been established. This diagnosis is not usually made before the age of about 15-16. Secondary amenorrhea means that the menstruation once established has ceased (temporarily or permanently). The most common type of hypohormonal amenorrhea is the menopause, or physiologic failure of ovarian function. The most common example of continuous hormonal amenorrhea is that due to pregnancy, when cyclic withdrawal is prevented by the placental secretions. These 2 conditions should always be considered before extensive diagnostic studies are undertaken.
Primary Amenorrhea Diagnosis
The principal diagnostic aids that are used in the study of amenorrhea are as follows:
- Vaginal smear for estrogen effect
- Endometrial biopsy
- Medical dilation and curretage
- Basal body temperature determination
- Urine determinations of 17-keto-steroids, FSH, pregnanediol, and pregnanetriol
- Culdoscopy and gynecography
- Chromosomal studies
- Pelvic exploratory operation or laparoscopy and gonadal biopsy
- Radioimmunoassays of FSH, LH, and prolactin, available for specific diagnosis of certain types of amenorrhea
- Plasma testosterone assay
- X-ray studies of the hypothalamic and pituitary areas
- In young females, bone age.
Because of the frequency with which delayed puberty is found in otherwise normal females, the diagnosis of primary amenorrhea usually is not made until the patient is clearly beyond the age at which normal menarche occurs. In the USA, the mean age at menarche is 12 and a half years. If menses have not started by age 16, primary amenorrhea is definitely present, and the cause should be investigated.
Most cases of primary amenorrhea are of the hypohormonal or ahormonal type. Exact diagnosis is essential to rule out an organic lesion along the hypo-thalamic-pituitary-gonadal axis. The chromosomal sex pattern must be determined in many cases. Laparoscopy or pelvic exploration may be required to establish the diagnosis. In large series, the most common cause has always been Turner's syndrome.
Primary Amenorrhea Causes
- Hypothalamic causes: Constitutional delay in onset, debility, serious organic illness, lack of LHRH (GnRH)
- Pituitary causes (with low or absent FSH): Suprasellar cyst, pituitary tumors (eosinophilic adenomas, chromophobe adenomas, basophilic adenomas), isolated lack of pituitary gonadotropins.
- Ovarian causes (with high FSH): Ovarian agenesis (Turner's syndrome), destruction of ovaries (eg, due to infection or, possibly, autoimmunity).
- Uterine causes: Malformations, congenital miillerian dysgenesis, imperforate hymen, hermaphroditism, unresponsive or atrophic endometrium.
- Miscellaneous causes: All forms of male pseudohermaphroditism (enzymatic defects in testosterone synthesis, androgen resistance syndromes), androgen excess syndromes (adrenal or ovarian tumors, polycystic ovaries).
Since primary amenorrhea is only a manifestation of multiple and often complex underlying defects, treatment must be individualized according to the specific cause.