Question

Case 1

A 26-year-old female complained of severe, dull, aching pain, and cramping in the lower abdomen. There were no other physical findings. A laparoscopy revealed the presence of ectopic endometrial tissue on the uterine wall and ovaries. Danazol (a synthetic androgen and inhibitor of gonadotropins), 600 mg/day, was prescribed for up to nine months to inhibit ovulation, suppress the growth of the abnormal endometrial tissue, and achieve appreciable symptomatic relief, with a 30% possibility of conception after withdrawal of the therapy.

• What is this condition called?
• What causes it?
• Why do you think oral hormonal contraceptives could also be used as a treatment – how can they help reduce the patients pain?
• Hormonal contraceptive therapy is also used to prevent pregnancy. Describe three ways oral contraceptive pills can prevent fertilization and pregnancy.

Case 2

A 67-year-old retired male went to his doctor, complaining initially of leg pain that started in his lower back, which then radiated down across the side of his thigh and over the front of his knee. Subsequently, he developed pain that radiated from his back to his front at two different levels: at the chest through the level of his nipples and also at the umbilicus.

His physician performed a history and physical, followed by laboratory tests. He discovered a hard nodule on his prostate and an elevation in several of the blood tests. His PSA (prostate specific antigen), an enzyme secreted by normal prostate tissue (0-4 ng/ml) was 450. Alkaline phosphatase was also elevated at 157 U/L, an indication of bone involvement.

A bone scan was ordered to visualize the bone involvement. (This test uses a calcium analogue attached to a radioactive tag. A special scanner can pick up images of this radioactivity and create an anatomical picture of the skeletal system. The radiation shows up as black spots on the film.)

Usually prostate cancer's growth is initially influenced by the presence of testosterone. If testosterone is removed by castration, the cancer will often shrink for some period of time before the remaining fraction of testosterone-independent cancer cells grow.

This gentleman was not interested in castration and asked if there was another way to treat this. He was treated was a single shot of a drug which is slowly released into the body over a three month time period. Within that time the patient noticed marked relief in his pain.

• What is the diagnosis of this gentleman?
• Why would the scan show bone abnormalities?
• Which endocrine organs are responsible for serum (blood) calcium levels?
• Describe a mechanism by which a drug could act on the anterior pituitary to lower the testosterone level in the human body.

Answer 1

1. Name of the condition:

• The condition of having ectopic endometrial tissue on the uterine wall is calles as Adenomyosis or internal endometriosis

2. Causes:

The exact cause of endometriosis is not known. The commonly associated causes are:
Retrograde menstruation: Normally, the menstrual blood flows from uterus through cervix and vagina. In retrograde menstruation, menstrual blood flows back through the fallopian tubes and into the pelvic cavity
Hormonal imbalance in the body
Surgical scars: from surgeries such as a Caesarean (C-section) or hysterectomy
Immune system problems
Genetics

3. Treatment:

Danazol is a steroid that has been shown to be effective at lowering hormonal levels in women with a diagnosis of endometriosis. This medication will cause the women to stop her menstrual cycles which will keep the endometrial growths from returning. It will also stop ovulation and the Lh hormonal swing that occurs during a normal menstrual cycle. Although ovulation is typically suppressed, there have been cases of pregnancy with this medication and non-hormonal birth control methods must be used in sexually active women, such as condoms, spermicidal lubricants, and diaphragms.

4. Oral contraceptive pills mechanism of action:

1.Inhibition of ovulation: Progestagen negative feedback decreases the pulse frequency of gonadotropin-releasing hormone (GnRH) release by the hypothalamus, which decreases the release of follicle-stimulating hormone (FSH) and greatly decreases the release of luteinizing hormone (LH) by the anterior pituitary. Decreased levels of FSH inhibit follicular development, preventing an increase in estradiol levels. Progestagen negative feedback and the lack of estrogen positive feedback on LH release prevent a mid-cycle LH surge. Inhibition of follicular development and the absence of a LH surge prevent ovulation.

2. Cervical mucus alteration: Inhibition of sperm penetration through the cervix into the upper genital tract (uterus and fallopian tubes) by decreasing the amount of and increasing the viscosity of the cervical mucus.

3. Endometrial hypoplasia: Endometrial effects that prevent implantation of an embryo in the uterus.