secondary amenorrhea

3\Amenorrhea and Oligomenorrhea with Breast Development and Normal Mullerian Structures

Disorders in which the patient has breast develop¬ment and a demonstrable cervix and uterine fundus on physical examination may cause primary as well as secondary amenorrhea, or may present as oligomen¬orrhea (menstrual cycles at greater than 35- to 45-day intervals).
All patients with menstrual bleeding disorders should be tested for pregnancy.. Initial history taking should include questions about the timing of thelarche, pubarche, and menarche. The timing and develop¬ment of the menstrual disorder (present since puberty or new), significant weight change, strenuous exercise activities, dietary habits, sexual activity, concomitant illnesses or complaints, abnormal facial or body hair growth, scalp hair loss, acne, and the presence or ab¬sence of hot flashes and vaginal dryness should be noted. A comprehensive list of medications and dietary supplements taken should be obtained.
In addition to a pregnancy test, the initial inves¬tigation of the amenorrheic patient should include an FSH level and a progestin challenge test. Failure of the patient to have withdrawal bleeding after receiving a progestational agent indicates significant hypoes- trogenism or hyperandrogenism, a uterine defect, or pregnancy. The absence of a withdrawal bleed after the administration of a progestational agent due to a uterine defect can be ruled out by the presence of withdrawal bleeding following sequential estrogen and progestin therapy.


A\UTERINE DEFECTS(normal estrogen level)

Women who do not have withdrawal bleeding after l hormonal challenge test and who have a history of uterine instrumentation, particularly a dilation and urettage, following vaginal delivery or pregnancy termination may have Asherman s syndrome. This interesting syndrome is characterized by intrauterine scarring (synechiae), and these patients may have normal ovulatory cycles with cyclic premenstrual symptoms. Patients with Asherman’s syndrome should be evaluated by hysterosalpingography or sonohysterography. the treatment of choice is hysteroscopic treatment with excision of the
synechiae ,followed by insertion of an IUCD with estrogen progesterone supplement for 3 months.

B\AMENORRHEA AND OLIGOMENORRHEA ASSOCIATED WITH HYPOESTROGENISM

The differential diagnosis for patients with amenor¬rhea associated with low levels of estrogen includes:
\ hypothalamic-pituitary dysfunction (hypothalamic amenorrhea) . have low FSH and prolactin levels.
\\ premature ovarian failure have high FSH and normal prolactin levels.
\\\hyper¬prolactinemia have high prolactin and low FSH levels.

\Hypothalamic-Pituitary Dysfunction
Patients with hypothalamic amenorrhea include women experiencing severe weight loss, women un¬dergoing excessive exercise resulting in low body fat, and women experiencing severe psychological stress. Also included are women with physical wasting from severe systemic diseases such as disseminated malig¬nancies and patients with pituitary or central nervous system lesions. In its most severe and life-threatening form, women may have pituitary failure or anorexia nervosa. All patients with hypothalamic-pituitary dysfunction should be evaluated for the status of the other pituitary hormones. Evaluation should also include an MRI of the hypothalamus and pituitary gland to exclude neo¬plastic and other lesions if it is uncertain whether the patient has one of the functional disorders described previously and the treatment is of the cause.

Sheehan ’ s s yndrome
This term describes hypopituitarism that presents in the
late postpartum period, and which is caused by haemorrhage
and hypotension at the time of delivery. The hypotension
results in avascular necrosis that affects the
anterior pituitary more commonly than the posterior
pituitary. Women most frequently present with failure of
lactation and subsequent amenorrhoea, but they may
have any feature of hypopituitarism including the more
subtle features of hypoadrenalism and hypothyroidism.


\\Premature Ovarian Failure

Premature ovarian failure is defined as ovarian failure before the age of 40 years. When it occurs in patients younger than 30 years of age, ovar¬ian failure may be caused by a chromosomal disor¬der. A karyotype is performed to exclude mosaicism (i.e., some cells bearing a Y chromosome). If cells with a Y chromosome are present, a gonadectomy to pre¬vent malignant transformation is indicated.
Other causes of premature ovarian failure include ovarian injury from surgery, radiation, or chemo¬therapy; galactosemia; carrier status of the fragile X syndrome; and autoimmunity.. It is not unusual for patients with premature ovarian fail¬ure to have episodes of normal ovarian and menstrual function. Patients with premature ovarian failure require hormonal therapy (estrogen and a progestin) to reduce the risk for osteoporosis.

\\\Amenorrhea and oligomenorrhea with hyperprolactinemia and galactorrhea:
The principal action of prolactin is to stimulate lacta¬tion. Hypersecretion of prolactin leads to gonadal dys¬function by interrupting the secretion of GnRH, which inhibits the release of LH and FSH and, in turn, im¬pairs gonadal steroidogenesis. The primary influence on prolactin secretion is tonic inhibition of dopamine input from the hypothalamus. Any event disrupting this inhibition can result in a rise in prolactin levels.
The consequences of hyperprolactinemia that are clinically significant include menstrual disturbances and galactorrhea
Causes of elevated prolactin


















C\Amenorrhea and oligomenorrhea with Normal Estrogen
Patients with amenorrhea or oligomenorrhea who consistently have normal levels of estrogen have a mild form of hypothalamic anovulation that may be caused by low body weight and exercise issues, psychological stress, recent pregnancy, or lactation. They may also have been treated with Depo Provera or combined hormonal contraceptives in the recent past. These iat¬rogenic causes usually resolve spontaneously within 6 months. Some women with amenorrhea or oligomen¬orrhea and normal estrogen levels may have a subclinical androgen excess disorder, such as a mild form of polycystic ovary syndrome (PCOS).
When contraception is not required in these an¬ovulatory women and fertility is not desired, periodic progestin withdrawal to confirm normal estrogen levels and protect their endometrium is appropriate. When fertility is not desired, combination hormonal contraception is appropriate.



D\Amenorrhea and Oligomenorrhea with Hyperandrogenism

Hyperandrogenism is the clinical manifestation of el¬evated levels of male hormones in women. Features may range from mild unwanted excess hair growth and acne to alopecia (hair loss), more extensive hirsutism, , masculinization and virilization. Hirsutism is the presence of male-like hair growth caused by conver¬sion of vellus to terminal hairs in areas such as the face, chest, abdomen, or upper thighs. Signs of masculiniza¬tion include loss of female body fat and decreased breast size. Virilization is the addition of temporal balding, deepening of the voice, and enlargement of the clitoris to any of the previous signs of excess male hormone. Androgens in women are normally pro¬duced in the ovaries and the adrenal glands Hyperandrogenic disorders may be di¬vided into functional and neoplastic disorders of the adrenal or ovary .














Diagrammatic representation of the steroid biosynthetic pathways. The asterisk refers to specific enzyme defects that result in congenital adrenal hyperplasia. Cmpd B, corticosterone; Cmpd S, ll-deoxycortisol; DHEA, dehydroepiandrosterone; DOC, desoxycorticosterone; HSD, hydroxysteroid dehydrogenase; OH, hydroxylase; P450c, cytochrome P450.











Hyperandrogenic Disorders

In general, hyperandrogenic disorders can be attributed to excessive secretion of androgens by the ovaries, by the adrenals, or both.

ADRENAL DISORDERS

Congenital Adrenal Hyperplasia
Congenital adrenal hyperplasia (CAH) is a general term used to describe an assortment of disorders that arise from inborn glandular enzyme deficiencies associated with the overproduction of steroids. The most common cause of CAH is 21-hydroxylase deficiency. CAH repre¬sents a spectrum of disorders, ranging from the severe salt-wasting form, to simple virilizing CAH, (e.g., salt loss or ambigu¬ous genitalia in female newborns) are present at birth or shortly thereafter. Alternatively the late onset) presents later in life, generally at the time of puberty or later. These patients (late onset) do not present with gen¬ital abnormalities, although they may develop hirsutism, acne, and menstrual and ovulatory irregularities.
Because 21-hydroxylase is responsible for the con¬version of 17-hydroxyprogesterone to 11-deoxycortisol), a deficiency in 21-hydroxylase results in an excessive accumulation of 17-hydroxyprogesterone. As a result, this enzyme disorder is marked by an elevated serum 17-hydroxyprogesterone level as well as increases in its metabolites androstenedione and testosterone. This disease is inherited as an autosomal recessive trait. CAH, are treated by the administration of glucocorticoids (e.g., 0.25 mg dexamethasone every other day at bedtime). However, many of these women also require suppression of ovarian androgen secretion using combination oral contraceptives and antiandrogens.

Cushing s Syndrome
Characteristic Cushinoid signs include truncal obesity, moon-like faces, hyper¬tension, easy bruisability, impaired glucose tolerance, muscle wasting, osteoporosis, abdominal striae, and supraclavicular and cervical spinal fat pads. Other manifestations include hirsutism, acne, and irregular menses. This is a rare cause of menstrual dysfunction in women.

Adrenal Neoplasms
Adrenal tumors causing hyperandrogenism without symptoms and signs of glucocorticoid excess are rare.


OVARIAN DISORDERS

Polycystic Ovary Syndrome
Six to 10% of women of reproductive age have some form of PCOS. This syndrome is a chronic condition that has been defined as anovulation or oligo-ovulation with clinical or laboratory evidence of hyperandrogen¬ism and without evidence of any other underlying con¬dition

Hyperandrogenic Insulin Resistance and Acanthosis Nigricans Syndrome
HAIR-AN syndrome is charac¬terized by extremely high circulating levels of insulin (>80 mU/mL basally or >500 mU/mL following an oral glucose challenge) due to severe insulin resistance. Because insulin is also a mitogenic hormone, these extremely elevated insulin levels result in hyperpla¬sia of the basal layers of the epidermal skin, leading to the development of acanthosis nigricans, a velvety, hyperpigmented change of the crease areas of the skin. In addition, because of the effect of in¬sulin on ovarian theca cells, the ovaries of many pa¬tients with the HAIR-AN syndrome are hyperthecotic. Patients with this disorder can be severely hyperandro¬genic and even present with virilization.

Ovarian Neoplasms
Androgen-producing ovarian tumors are extremely un¬common, and include Sertoli-Leydig, hilus, and lipoid cell tumors



Diagnosis of Secondary Amenorrhea




A diagnostic approach to secondary amenorrhea. (DHEA-S = dehydroepiandrosterone sulfate; FSH = follicle-stimulating hormone; LH = luteinizing hormone; MRI = magnetic resonance imaging; TSH =