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Managing Amenorrhea 2

Written by Sanjay Gole ( 28 June, 2015 6:06 pm

Category Archives Articles (, Review of the month archives

Dr Ameya C Purandare

Member of the Managing Council of MOGS

E-mail: (

It is absolutely essential to determine which organ is dysfunctional and then to establish the precise cause so
that specific treatment can be advised
Any patient with amenorrhea who has a uterus pregnancy should be first ruled out and serum levels of
thyroid-stimulating hormone (TSH) and prolactin estimated. Galactorrhea should be identified by clinical

Chart 1: Work-Up for Primary Amenorrhea

Chart 2: Work-up for secondary amenorrhea

Chart 3: Work-Up for AmenorrheaGalactorrheaHyperprolactinemia.

Table 5: Causes Of Eugonadotropic Eugonadism
(Progestin-Challenge Positive).

Mild hypothalamic dysfunction

1. Psychological disorder
2. Emotional stress
3. Weight loss
4. Obesity
5. Exercise induced
6. Idiopathic

2. Ovarian tumor
3. Adrenal tumor
4. Cushings syndrome
5. Congenital and maturity-onset adrenal hyperplasia
Systemic disease

Addisons disease
Chronic renal failure
Diagnosis of Amenorrhea Associated with Galactorrhea-Hyperprolactinemia

Table 6: Causes Of Galactorrhea-Hyperprolactinemia

Pituitary tumors secreting prolactin

1. Macroadenomas (> 10 mm)
2. Microadenomas (< 10 mm)
Idiopathic hyperprolactinemia
Drug-induced hyperprolactinemia

1. Dopamine antagonists
1. Phenothiazines
2. Thioxanthenes
3. Butyrophenone
4. Diphenylbutylpiperidine
2. Catecholamine-depleting agents
3. False transmitters (-methyldopa)
Interruption of normal hypothalamicpituitary relationship

1. Pituitary stalk section

Peripheral neural stimulation

1. Chest wall stimulation

2. Nipple stimulation
3. Spinal cord lesion
Central nervous system disease

Pineal tumors
Hypothalamic tumors
Pseudotumor cerebri

Management Of Patients Desiring PregnancyOvulation Induction

a)Ovulation Induction in Patients with Primary Ovarian Failure

Patients with primary ovarian failure can be made to ovulate only under very rarely. Patients with reversible
ovarian failure due to autoimmune oophoritis, can be treated with corticosteroids.In vitro IVF with oocytes
donation is the only option by which they can have children.Any patient with a Y chromosome should undergo
oophorectomy to prevent tumor development.

b)Ovulation Induction in Patients with Hypoestrogenic Hypothalamic Amenorrhea (Progestin-

Challenge Negative)
In these patients with low estrogen levels, the pituitary does not release high quantities of LH and FSH.
Injections of exogenous gonadotropins (human recombinant follicle-stimulating hormone [hrFSH] or human
menopausal gonadotropin [hMG]) is usually first-line therapy. Patients showing some ovarian stimulation by
clomiphene can be treated with a combination of clomiphene and hMGthe advantage being a reduction in
the amount of hMG required and thus a substantial costreduction. Ovulation induction with gonadotropins
must be carefully monitored with serial ultrasound and estradiol determinations to avoid hyperstimulation. If
a potentially reversible cause of amenorrhea can be identified like marked weight loss, it should be corrected.
c)Ovulation Induction in Patients Who Bleed in Response to Progestin Challenge
Most of these patients respond to clomiphene citrate. The starting dose is 50 mg orally daily for 5 days. This
can be increased to a maximum of 250 mg orally daily in 50-mg increments until ovulation is induced. This
medication is FDA-approved for use up to 150 mg/d. Ovulation occurs 510 days after the last dose.
Patients with elevated androgens may not respond to clomiphene citrate may respond to combined treatment
with an oral hypoglycemic agent (metformin) and clomiphene. If clomiphene therapy with or without
metformin is ineffective, gonadotropin therapy may be attempted. Care must be taken in using FSH in these
patients, as they are likely to become hyperstimulated.

Laparoscopic ovarian drilling (LOD) is a surgical method of ovulation induction in PCOS patients. LOD involves
electrocautery or laser drilling with the goal of creating foci of laser or thermal damage in the cortex and
ovarian stroma. The mechanism of action may involve destruction of androgen-producing stromal cells, a
sudden drop in ovarian androgen levels, improved follicular microenvironment, or increased gonadotropin
secretion. This procedure may cause postoperative pelvic adhesions, resulting in tubal compromise.

d)Ovulation Induction in Patients with Amenorrhea-Galactorrhea with Pituitary Macroadenoma

Dopamine agonist drugs such as cabergoline and bromocriptine are the first-line treatment of
hyperprolactinemia of any cause, including macroadenomas. These drugs can decrease prolactin secretion
and tumor size. Surgical therapy, transsphenoidal or frontal removal of the pituitary adenoma or the entire
gland, may be required if tumor size or secretion are resistant to dopamine agonists; the lesion is rapidly
enlarging or causing symptoms such as visual changes or headaches; or in women with giant adenomas (> 3
cm) who wish to discontinue agonist treatment for conception and the duration of pregnancy.

e)Ovulation Induction in Patients with Amenorrhea-Galactorrhea without Macroadenoma (Including

Patients with Microadenomas)
These patients ovulate readily in response to dopamine agonist treatment, with dose titrated until serum
prolactin is normal. Patients are maintained on the lowest dose. Once pregnancy has been achieved, the agent
can be discontinued. Patients with macroadenomas may need to continue therapy throughout pregnancy to
avoid further growth of the lesion.

Patients taking drugs that raise the prolactin level should discontinue them if possible, but continued use of
such drugs is not a contraindication to therapy.

f)Ovulation Induction in Patients with Hypothyroidism

Amenorrheic patients with hypothyroidism respond to thyroid replacement therapy.

Management Of Patients Not Desiring Pregnancy

Patients who are hypoestrogenic must be treated with a combination of estrogen and progesterone to
maintain bone density and prevent genital atrophy.
Oral contraceptives are effective replacement therapy for most women.

Combinations of 0.6251.25 mg of conjugated estrogens orally daily on days 1 through 25 of the cycle with 5
10 mg of medroxyprogesterone acetate on days 16 through 25 are an alternative. Calcium intake should be 1
1.5 g of elemental calcium daily.
Patients who respond to the progestin challenge require progestin administration to prevent the development
of endometrial hyperplasia and carcinoma.
Oral contraceptive pills may be used for regularization of the menstrual cycle.. Alternatively,
medroxyprogesterone acetate, 10 mg orally daily for 1013 days every month or every other month, is
sufficient to induce withdrawal bleeding and to prevent the development of endometrial hyperplasia.

Patients with hyperprolactinemia need periodic prolactin measurements and radiographic cone views of the
sella turcica to check for the development of macroadenoma.

Management Of Uterine Causes Of Amenorrhea-Surgical Treatment

Uterine abnormality Surgical treatment

Mllerian agenesis 1. Treatment should be offered when the patient is

contemplating sexual activity involves creation of neovagina
2. Nonsurgical creation of a vagina using serial vaginal dilators
3. McIndoe procedure involves the creation of a cavity by
dissection between the urethra and bladder anteriorly and
the perineal body and rectum posteriorly. The cavity is lined
by a split-thickness skin graft overlying a plastic or soft
silicone mold
4. Laparoscopic vaginoplasty (Vecchietti procedure)
Vaginal agenesis 1. Same as Mllerian agenesis

Transverse Vaginal Septum 1. If the diagnosis of a complete septum is established prior to

menarche, it should be incised, creating an aperture to allow
2. Incision of a complete septum is most easily accomplished
when the upper vagina is distended and the membrane is
bulging, reducing the risk of injury to adjacent structures.
3. Surgical correction of vaginal narrowing should be
performed only when the patient is contemplating initiation
of sexual activity.
4. End-to-end reanastomosis of the upper and lower vaginal
mucosa, which may be accomplished with the aid of a Lucite
Imperforate Hymen 1. Hymenectomy involving a cruciate incision on the hymenal
membrane to drain the collected menstrual blood and
maintain patency of the vaginal tract
Ashermans Syndrome 1. Hysteroscopic adhesiolysis with post procedure estrogenic
stimulation of the endometrium

The complications of amenorrhea can be numerous, ranging from infertility to psychosocial developmental
delays with lack of normal physical sexual development.
Hypoestrogenic patients can develop severe osteoporosis and fractures. The complications associated with
amenorrhea in patients who respond to progestin challenge are endometrial hyperplasia and carcinoma
resulting from unopposed estrogen stimulation.


The overall prognosis for amenorrhea is good.

One must remember and reiterate to the patient and her relatives that it is usually not a life-threatening
clinical event and with proper evaluation the precise etiology can be diagnosed and treated.
Many patients with hypothalamic amenorrhea will spontaneously recover normal menstrual cycles. Virtually all
amenorrheic women who do not have premature ovarian failure can be made to ovulate with a dopamine
agonist, clomiphene citrate, insulin-sensitizing agents, and gonadotropins.


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2. ASRM: Practice Committee of the American Society for Reproductive Medicine. Current evaluation of
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Washington, D.C.: ACOG, 1989.
4. Speroff L, Fritz MA. Amenorrhea. In: Clinical gynecologic endocrinology and infertility. 7th ed.
Philadelphia, Pa.: Lippincott Williams & Wilkins, 2005;401-64.
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6. McIver B, Romanski SA, Nippoldt TB. Evaluation and management of amenorrhea. Mayo Clin Proc
7. Laufer MR, Floor AE, Parsons KE, Kuntz KM, Barbieri RL. Hormone testing in women with adult onset
amenorrhea. Gynecol Obstet Invest 1995;40:200-3.
8. Pickett CA. Diagnosis and management of pituitary tumors: recent advances. Prim Care 2003;30:765-89.
9. Folch M, Pigem I, Konje JC. Mllerian agenesis: etiology, diagnosis, and management. Obstet Gynecol
Surv 2000;55:644-9.
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guidelines for obstetrician-gynecologists: number 41, December 2002. Obstet Gynecol 2002;100:1389-
11. Anasti JN. Premature ovarian failure: an update. Fertil Steril 1998;70:1-15.

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