Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Reexamination Certificate
2000-08-04
2004-05-04
Myers, Carla J. (Department: 1634)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
C435S091200, C536S023500, C536S024310, C536S024330
Reexamination Certificate
active
06730476
ABSTRACT:
1. BACKGROUND OF THE INVENTION
Menopause is defined as the permanent cessation of menstruation caused by failure of ovarian follicular development in the presence of elevated gonadotrophin levels.
Comprehensive Gynecology
(eds. Mishell et al 1997). A hallmark of menopause is the decrease in ovarian follicular estrogen synthesis, although this is only one aspect of the array of physiological events that accompanies the climacteric. Symptoms accompanying menopause vary from woman to woman, but usually include some component of vasomotor instability or hot flashes, often accompanied by psychological symptoms like mood swings and irritability. The loss of estrogen predisposes to coronary artery disease. Loss of estrogen further results in loss of overall bone mineral content caused by an increased resorption of bone without a correlative increase in bone formation. Unabated net loss of bone structural integrity following menopause can culminate in clinically significant osteoporosis. The severity of these climacteric symptoms can be substantially reduced with estrogen replacement therapy. These symptoms represent formidable challenges to the health care system. Recognizing that the current average life expectancy for a woman in the U.S. is 78 years, one can readily calculate that a substantial portion of a woman's lifespan will be post-menopausal. In 1990, for example, there were more than 50 million women in the U.S. over 50 years of age.
The mean age of physiological menopause in the U.S. is between 51 and 52 years of age, with a range between 45 and 55 years old distributed along a normal curve. Stanford et al.,
J. Chron. Dis
40:995, 1987. About 10% of women in the U.S. undergo menopause before age 46; 1% of U.S. women enter menopause before age 40. If a woman becomes menopausal before age 40, the condition is termed premature ovarian failure. A variety of factors have been identified that correlate weakly with age of menopause, including number of pregnancies, use of oral contraceptives, duration of lactation, age at menarche, age at last pregnancy, race, height, weight, education or occupational history. Cassou et al.,
Maturitas
26:165-74, 1997. Cigarette smoking, however, has been observed to decrease the age of onset of menopause by about two years. Menopause may also be therapeutically induced, either chemically, surgically or via radiation (e.g. to reduce the risk of developing breast cancer associated with exposure to estrogens).
Diagnosis of menopause may be made clinically by observing the absence of menses for a year. Most women experience progressive menstrual irregularity that presages menopause. The time between the onset of menstrual irregularity and menopause is called the perimenopause. The median age at onset of perimenopause is 47.5 years; its median length is 4 years. McKinlay et al.,
Maturitas
14:103, 1992. Prior to the onset of the perimenopause, the length of the menstrual cycle tends to decrease in length, due to the decreased duration of follicular functioning. Munster et al.,
Br. J. Obstet./Gynaecol.
99:422, 1992. About 10% of women do not enter a perimenopausal phase, rather continuing to have regular cycles until menses suddenly stop.
Hormonal changes often precede changes in menstrual patterns, and early diagnosis for menopause and perimenopause has traditionally involved the measurement of follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels. A significant increase in both FSH and LH levels occurs about 5 years before menopause, with the FSH increase more prominent than the LH increase. Levels of these gonadotrophins peak about one year postmenopausally for LH and two to three years after menopause for FSH. The incidence of ovulatory cycles, measured by elevated luteal phase progesterone levels, decreases from 60% during the 5-6 years before menopause to 5% in the 6 months before menopause. Estrogen levels fall as the number of ovulatory cycles decreases, particularly during the 6-12 months before menopause. FSH release, mainly controlled by inhibin, remains elevated even in the presence of post-menopausal hormone replacement. An initial fall in inhibin level is an early indication of diminishing ovarian function. FSH level rises accordingly, suggesting the woman's entry into the perimenopausal stage of reproductive function. Initial changes in FSH and inhibin are often transitory. It is therefore important to demonstrate a sustained increase in FSH. This value, combined with low estradiol levels, is used to diagnose the onset of permanent ovarian failure.
Diagnosis of menopause and perimenopause thus tends to be possible only after major changes in the endocrine system have already occurred. A younger woman without premonitory perimenopausal symptoms may have no reason to have her hormone levels measured; she may thus enter early onset menopause (EOM) without any warning. In such a patient, hormonal analysis may not yield a diagnosis until after EOM has taken place. Hormone assays in a younger patient may only be transiently abnormal prior to the onset of permanent ovarian failure. The younger patient destined for EOM is a particularly appropriate subject for early medical intervention (e.g. estrogen replacement therapy). Family planning needs to be considered if early loss of reproductive function is anticipated. Decisions about childbearing and preservation of fertilized ova should be undertaken at an early age in such a patient. Further medical advice is important about the value of hormone replacement therapy for a young woman who faces prolonged post-menopausal levels of estrogen. The relative contribution of estrogen replacement to bone strength and cardiovascular health must be balanced against the possibility of breast cancer development, in response to hormone replacement therapy (HRT).
A complex set of endocrine mechanisms regulates the female reproductive system. Understanding the interrelationship of these mechanisms provides the basis for discerning the factors involved in physiological menopause and EOM. No single organ secretes all the hormones responsible for these processes. The hypothalamus, the pituitary gland, and the ovaries, are primary organs, although adrenal and thyroid hormones also play roles. Feedback mechanisms enable the various hormones to affect the production of other hormones within the reproductive system.
The central nervous system controls reproductive hormone production through its release of gonadotropin-releasing hormone (GnRH). This hormone, produced by the hypothalamus, in turn affects gonadotropin secretion by the pituitary. GnRH secretion is responsive to levels of brain neurotransmitters, in particular the two catecholamines dopamine and norepinephrine. Opioids and prostaglandins in the hypothalamus have also been identified as regulators of GnRH release. The neurotransmitter serotonin has not been associated with GnRH release, but it does stimulate the release of prolactin by the hypothalamus. Other peptides have been identified in the brain that act as neurotransmitters. For example, the peptides activin and inhibin, members of TGF-beta superfamily, have been identified within the brain. These substances have opposite effects on pituitary gonadotropin secretion: inhibin diminishes FSH production but does not affect the release of LH; activin stimulates FSH but not LH.
GnRH, when it reaches the anterior lobe of the pituitary, stimulates the production of LH and FSH from the gonadotrophs in the pituitary gland. GnRH only acts to stimulate the production of the gonadotropic hormones. The periodic release of LH and FSH by the pituitary is responsive not only to GnRH but also to feedback systems involving the target organ of these hormones, the ovary. LH acts primarily on the thecal cells of the ovary to induce the synthesis of steroids, while FSH acts primarily on the granulosa cells of the ovary to stimulate the growth of the ovarian follicles. Both types of ovarian cells are thought to be involved in estrogen production. LH acts on the thecal cells to produce the an
Duff Gordon
Kornman Kenneth
van Dijk Simon
Elrifi, Esq. Ivor R.
Interleukin Genetics Inc.
Kowakiewicz, Esq. Cynthia A.
Mintz Levin Cohn Ferris Glovsky and Popeo P.C.
Myers Carla J.
LandOfFree
Methods of diagnosing early-onset menopause does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Methods of diagnosing early-onset menopause, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods of diagnosing early-onset menopause will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3242334