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Amenorrhea

Amenorrhea is a condition where a woman of reproductive age does not get her regular menstrual periods. Amenorrhea can be primary or secondary Amenorrhea.

Primary Amenorrhea: This condition occurs when the first menstrual period of a girl is delayed or does begin by 16 years. This could be due to delay in pubertal development. Birth defects in the reproductive system can often lead to primary Amenorrhea as also tumor in the hypothalamus or pituitary gland. Abnormal chromosome or genetic defects can be a cause. Hypothyroidism, hyperthyroidism, Cushing's disease and congenital heart disease can be a cause for primary Amenorrhea. Often the cause is not known. Symptoms include acne and excess body hair, headaches and vision problems.

Secondary Amenorrhea: This kind of Amenorrhea occurs in women during their reproductive period. Secondary Amenorrhea is a situation where the menstrual period is absent for about 3 months. This is most often due to pregnancy and breastfeeding. Symptoms of secondary Amenorrhea are mood fluctuations, goiter, vaginal dryness, depression and nausea.

If any systemic condition is the cause for Amenorrhea, appropriate treatment often leads to the start of menstruation. Often anorexia or over exercising can lead to Amenorrhea. Endocrine disorders, hormonal imbalance, PCOS and use of birth control pills often lead to Amenorrhea. Other causes for Amenorrhea include malfunctioning ovaries and stress. Women who complain of Amenorrhea are given a physical examination by the gynecologist. Blood tests for prolactin and T3, T4 and FSH are done. Other blood tests include test for serum progesterone. Pelvic ultrasound is done to check for any abnormalities.


Asherman's Syndrome

Asherman's syndrome refers to the formation of adhesions or scar tissues on the endometrium (uterine lining). Most often endometrial scarring occurs as a result of scraping of tissue from the uterine wall while performing dilation and curettage (D& C). Though D&C is mainly responsible for adhesions, uterine surgery and severe infections of the endometrium such as genital tuberculosis are some of the other factors that cause Asherman's syndrome. Normally, Asherman's syndrome shows up with decreased menstrual flow or even amenorrhea, cramping, abdominal pain and is even associated with infertility and recurrent miscarriages.


Causes of Asherman's syndrome

D&C procedure is performed for miscarriages, excess bleeding, elective abortion or to remove the retained products of conception. Some gynecological disorders call for uterine surgery. Sometimes trauma occurs to the uterine lining while performing D&C procedure or other surgery. In case of damage, the wound begins to heal and in the process, fuses with the affected portion causing adhesions. The risk of Asherman's syndrome increases with repeated D&Cs.


Symptoms of Asherman's syndrome

Infertility
Menstrual disorders such as Hypomenorrhea or amenorrhea
Repeated miscarriage
Pelvic pain as scar tissue blocks the menstrual flow.


Diagnosis and treatment of Asherman's syndrome

Hysteroscopy is the widely used method to diagnose the Asherman's syndrome as it allows the doctor to have a complete view of the uterus directly. However other methods such as sonohysterography (SHG), hysterosalpingogram (HSG) and transvaginal ultrasound examination are also used to evaluate adhesions. Blood tests are done to detect tuberculosis or schistosomiasis.

Asherman's syndrome is normally treated with surgery to remove the adhesions or scar tissue. The surgery involves hysteroscopy procedure wherein scar tissue is removed by using small instruments, micro scissors and a camera. Once the scar tissue is removed, an intra uterine balloon is placed inside the uterus to keep the uterine cavity open. This procedure aids the healing process and prevents adhesions from returning. Patient may also be prescribed oral estrogen medications for promoting growth of regular uterine lining. Patient may be called in for review hysteroscopy after two weeks of the procedure to make sure that there is no reformation of adhesions.


GnRH

Gonadotropin-releasing hormone (GnRH) is a neurohormone consisting of ten amino acids which is produced by the arcuate nuclei of the hypothalamus. It is integral for starting the reproductive hormone cascade.


GnRH is secreted in the hypothalamus which is part of the brain. The hypothalamus is part of the 'Hypothalamus - Pituitary - Gonad' axis which regulates the reproductive system in men and women. Secretion of GnRH by the hypothalamus is delivered through a direct pathway between the hypothalamus and pituitary. GnRH stimulates the synthesis and secretion of two gonadotrophins namely, lutenizing hormone (LH) and follicle stimulating hormone (FSH) by the anterior pituitary gland. Controlled by internal and external factors, GnRH acts in a negative feedback loop. For instance, if there is excess FSH, LH or testosterone, then these hormones will inhibit GnRH production.


Lifestyles can also affect GnRH secretion. Lack of exercise, poor diet, opiad drugs and excessive stress can negatively affect GnRH production. What is so striking in GnRH is that under normal circumstances, GnRH is released at intervals of 90 to 120 minutes. Hence, in patients with GnRH deficiency, the releasing hormone should be administered in pulses. Constant administration of GnRH also suppresses gonadotropin secretion especially in children in puberty stage and in men with prostate cancer.


Why is GnRH treatment used?

This hormone is produced by the hypothalamus and it stimulates the pituitary gland to produce LH and FSH. Lack of GnRH in the hypothalamus can halt testosterone production in the testicles of men. In women, abnormal GnRH levels can be responsible for ovulatory disorders.

This is commonly used when Clomid treatment has not stimulated egg follicles to develop on the ovaries. GnRH works effectively to replace the natural GnRH in women and men who do not produce enough of it. Failure of release of GnRH can result in deficiency that can be partial or complete.


In a woman who is not ovulating because of lack of stimulation from hypothalamus.

In a man who is not producing sperm because his hypothalamus is not stimulating the hormones that trigger sperm production.

The use of GnRH can result in multiple pregnancies.

Some studies report that the pregnancy rate after treatment with GnRH is about 20%.


Side effects

Some side effects include:


  • Breathing trouble
  • Swelling of face, lips, tongue and throat
  • Itching and redness at the site of the intravenous catheter
  • Infection at the site of the IV catheter
  • Ovarian hyper stimulation syndrome - GnRH poses less risk of this syndrome than does human menopausal Gonadotropin and other treatments for ovulation.

The small pump that is used for GnRH may bother some people and treatment requires daily monitoring by a doctor.

Although clinicians and scientists have observed the findings of olfactory disturbances and reproductive dysfunction, the syndrome comprising complete GnRH deficiency and lack of olfactory senses is named Kallmann Syndrome after the American geneticist Kallmann who identified this disorder in 1944.


Treatment

The choice of therapy depends upon the patient's desire to achieve one or more of the following options:


  • Secondary sexual characteristics
  • Fertility
  • Bone and muscle mass

In males, treatment is decided to provide androgen replacement. The patient's age, potential adverse effects of therapy, patient's desire for fertility are considered. In the prepubertal male, GnRH stimulates penile growth, body and facial hair growth, bone and muscle development and voice changes. Androgens also stimulate growth hormone production, contributing to the adolescent growth spurt. Male androgen deficiency can result in social ridicule and therefore starting androgen therapy around age 14-15 is prudent.

Oral, injectable and transdermal and implantable pellets formulation are available for treatment of males with Kallmann syndrome. Oral androgen preparations should not be used due to their toxic effects on the liver and adverse effects on lipids. Injectable long-acting testosterone are low-cost, relatively safe and effective. The disadvantages include intramuscular injection and non physiologic pattern of testosterone over the dosing interval. There could be wide swings in libido in some men.


Transdermal patches and gel preparation of testosterone are currently available - adverse effect with these formulations include skin reactions at the application. In females as in males, treatment depends upon age and fertility desires. Estrogen replacement is a must to prevent osteoporosis.

Oral preparations, transdermal patches, vaginal cream and rings are available for standard hormone replacement therapy. Transdermally administered 17 beta estradiol has been shown as an effective regimen for preventing bone loss in normal menopausal women.

Women with intact uterus receive a cyclical progestin to accompany estradiol treatment. Optimal hormone therapy depends upon whether the patient has primary or secondary amenorrhea. Gradual dose escalation results in optimal breast development and allows time for young woman to adjust psychologically to her physical maturation.


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Bibliography / Reference

Collection of Pages - Last revised Date: September 15, 2019