Therapeutic measures may include specific therapies (medical or surgical) aimed at correcting the primary cause of amenorrhea, hormone therapy to initiate and maintain secondary sexual characteristics and provide symptomatic relief, treatments to maximize and maintain peak bone mass including hormone therapy, calcium, and vitamin D for cases where circulating estrogen levels are low, and ovulation induction for patients desiring pregnancy.
A complex hormonal interaction must take place in order for normal menstruation to occur. The hypothalamus must secrete gonadotropin-releasing hormone (GnRH) in a pulsatile fashion, which is modulated by neurotransmitters and hormones. The GnRH stimulates secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary, which
Causes of Primary Amenorrhea
Hypergonadotropic Hypogonadism Associated with Absence of Secondary Sexual Characteristics promotes ovarian follicular development and ovulation. A normally functioning ovarian follicle secretes estrogen; after ovulation, the follicle is converted to corpus luteum, and progesterone is secreted in addition to estrogen. These hormones stimulate endometrial development. If pregnancy does not occur, estrogen and progesterone secretion decrease and withdrawal bleeding begins. If any of the components (hypothalamus, pituitary, ovary, uterus, and outﬂow tract) are nonfunctional, bleeding cannot occur.
The mean age of menarche became younger during this century. Therefore, the definition of primary amenorrhea changed: Primary amenorrhea is defined as the absence of menses by 13 years of age when there is no visible development of secondary sexual characteristics or by 15 years of age in the presence of normal secondary sexual characteristics. The ages defining primary amenorrhea were decreased by 1 year to continue to represent two standard deviations above the mean age of developing secondary sexual characteristics and menses (1). Failure to begin breast development by age 13 warrants investigation. A woman who previously menstruated can develop secondary amenorrhea, which is defined as absence of menstruation for three normal menstrual cycles (2). A woman with regular cycles and a delay of menses of even a week may warrant assessment with a pregnancy test. It is reasonable to evaluate a woman who has fewer than nine cycles per year. With a few exceptions, the causes of primary amenorrhea are similar to the causes of secondary amenorrhea.
Patients may develop slight alterations in the hypothalamic–pituitary–ovarian axis that are not severe enough to cause amenorrhea but instead cause irregular menses (oligomenorrhea) associated with absent or infrequent ovulation. These patients may bleed excessively during menstruation because estrogen is unopposed. The etiologies of oligomenorrhea overlap with the etiologies of amenorrhea, with the exception that certain anatomic (e.g., absent uterine development) and karyotypic abnormalities (e.g., Turner syndrome), are largely associated with primary amenorrhea.
The World Health Organization (WHO) described three classes of amenorrhea. WHO Group I includes women with no evidence of endogenous estrogen production, normal or low FSH levels, normal prolactin levels, and no lesion in the hypothalamic-pituitary region. WHO Group II is associated with evidence of estrogen production and normal levels of prolactin and FSH. WHO Group III includes individuals with elevated serum FSH indicating gonadal insufficiency or failure.
To detect the cause of amenorrhea, it is useful to determine whether secondary sexual characteristics are present (Fig. 30.1). The absence of secondary sexual characteristics indicates that a woman was never exposed to estrogen.