Ovarian Lifecycle

Normal Events

Ovulation Detection

Ovulation Dysfunction
  • Ovarian Dysfunction
  • Pituitary Dysfunction
    ¬ Hypothyroidism
    ¬ Hyperthyroidism
    ¬ Postpartum Depression
    ¬ Hyperprolactinemia
    ¬ Crushing's Syndrome
    ¬ Acromegaly
  • Hypothalamic &
      CNS Dysfunction

Clinical Evaluation

Treatment Options

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The pituitary causes for ovulatory dysfunctions include:

(1) Hypothyroidism
The mechanism for the ovulatory dysfunction associated with hypothyroidism has not been entirely worked out.

Hypothyroidism probably interferes with ovulation via an increase in circulating active estrogen. Increased bioactive estrogen may be due to decreased metabolism of estrogen in the liver (seen with both hypothyroidism and hyperthyroidism) or due to decreased levels of the protein that binds estrogen in the circulation. Sex hormone binding globulin (SHBG) decreases the bioactivity of bound hormones by reducing the “free” (bioactive) fraction of the hormone. Persistent elevations of bioactive estrogen can interfere with follicular growth and can disrupt the midcycle preovulatory LH and FSH surges that are required for normal ovulation.

Hypothyroidism may also interfere with ovulation through an elevation in TRH. With decreased circulating thyroid hormone there is enhanced secretion of hypothalamic thyrotropin releasing hormone (TRH), which acts on the brain’s pituitary gland to release thyrotropin or thyroid stimulating hormone (TSH). This TSH then stimulates the synthesis and release of thyroid hormone in a normal thyroid gland. Elevated TRH can “crosstalk” within the pituitary gland to release other pituitary hormones such as prolactin. Elevated prolactin levels are known to interfere with ovulation .

(2) Hyperthyroidism
The mechanism for the ovulatory dysfunction associated with hyperthyroidism is also not entirely clear.

There may be elevated bioactive estrogen concentrations either due to decreased liver metabolism of estrogens or due to an increase in the activity of the enzyme that forms estrogens (called aromatase). Persistent elevations of estrogen interfere with follicular growth and can disrupt the midcycle LH and FSH surges.

(3) Excessive circulating prolactin
The mechanism for this association between excess prolactin concentration and ovulatory dysfunction is not entirely clear.

Increased prolactin released from the pituitary gland can increase the brain’s dopamine levels (which will then normally feedback to decrease the prolactin secretion) and increased dopamine can inhibit GnRH release from the hypothalamus to in turn decrease pituitary FSH and LH secretion. A decrease in FSH may be the basis for most prolactin associated ovulatory problems.

There are prolactin receptors on the adrenal glands. The adrenal glands may respond to increased prolactin by increasing their own androgenic hormones. These adrenal androgenic hormones can also interfere with ovulation.

Prolactin can decrease progesterone production by granulosa cells (the cells that line ovarian follicles) in culture. If there is a direct effect of prolactin on granulosa cell progesterone production in vivo (in a woman’s ovaries) then this could lead to the ovulatory dysfunction called a luteal phase defect.

(4) Non-prolactin secreting pituitary tumors
The more common of these are ACTH secreting tumors (resulting in Cushing’s syndrome) and Growth Hormone secreting tumors (resulting in acromegaly). Also, there are gonadotropin secreting tumors of the pituitary that secrete excess amounts of FSH (and rarely LH) that may result in an ovulatory dysfunction but rarely amenorrhea (these frequently go undetected due to the difficulty in finding these tumors with the relative lack of identifiable symptoms).

(5) Pituitary damage
Thrombosis or hemorrhage around the pituitary gland can result in permanent destruction and amenorrhea. Rarely, this is due to a hypotensive episode occurring during a severe postpartum hemorrhage, called “Sheehan’s syndrome.” In the situation where pituitary damage is the cause of the ovulatory dysfunction, it is very important to evaluate the non reproductive pituitary hormones as well since they may also be insufficient. Adrenal insufficiency due to a deficiency of pituitary ACTH can be life threatening.

(6) Empty sella syndrome
This is a disorder characterized by a congenital imperfection in the sellar diaphragm that allows for the herniation of both the subarachanoid space and cerebrospinal fluid into the sella turcica flattening the pituitary gland and resulting in increased prolactin and decreased FSH and LH secretion. Amenorrhea and galactorrhea are associated with the empty sella syndrome. Some women have a nasal cerebrospinal fluid discharge or headaches. On radiologic imaging the sella turcica looks empty, to give the condition its name.

(7) Medications
Progesterone or progestagenic medications can inhibit ovulation. Excess circulating progesterone concentration just prior to the LH surge will possibly inhibit the LH surge and thereby prevent ovulation. This is one of the mechanisms of the progesterone only birth control pills. If progesterone supplementation for luteal support is (accidentally) taken during the follicular phase of the cycle, this can also inhibit ovulation

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