ARTIFICIAL INSEMINATION IN FARM ANIMALS - Phenix-Vet

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274Artificial Insemination in Farm Animals5. The peri-menopausal transitionThere is only one marker, menstrual irregularity that can be used to objectively define andestablish what is called the peri-menopausal transition. This irregularity will be perceivedby patients as skipped menstrual periods or longer durations (about 40 to 60 days) betweenperiods (Harlow SD, et al., 2008) There is no universal pattern; each woman will perceive achange that is her own individual characteristic alteration. Literally means “about or aroundthe menopause.” Generally speaking, the term “menopausal transition” is preferred overperi-menopause and climacteric.The menopause is that point in time when permanent cessation of menstruation occursfollowing the loss of ovarian activity. Menopause is derived from the Greek words men(month) and pausis (cessation). The years prior to menopause that encompass the changefrom normal ovulatory cycles to cessation of menses are known as the peri-menopausaltransitional years, marked by irregularity of menstrual cycles. Climacteric, an older, moregeneral, and less precise term, indicates the period of time when a woman passes from thereproductive stage of life through the peri-menopausal transition and the menopause to thepostmenopausal years (Treloar AE, et al., 1967). Menarche is followed by approximately 5–7years of relatively long cycles at first, and then there is increasing regularity as cyclesshorten to reach the usual reproductive age pattern. In the 40s, cycles begin to lengthenagain. The highest incidence of anovulatory cycles is under age 20 and over age 40 (CollettME, et al., 1954). At age 25, over 40% of cycles are between 25 and 28 days in length; from 25to 35, over 60% are between 25 and 28 days. The perfect 28-day cycle is indeed the mostcommon mode, but it totalled only 12.4% of Vollman’s study cycles. Overall, approximately15% of reproductive-age cycles are 28 days in length. Only 0.5% of women experience acycle less than 21 days long, and only 0.9% a cycle greater than 35 days (Munster K, et al.,1992).Most women have cycles that last from 24 to 35 days, but at least 20% of women experienceirregular cycles (Belsey EM & Pinol APY, 1997). When women are in their 40s, anovulationbecomes more prevalent, and prior to anovulation, menstrual cycle length increases,beginning 2 to 8 years before menopause (Treloar AE, et al., 1967). Cycles greater than 40days in length are prevalent in the year before menopause (Ferrell RJ, et al) The duration ofthe follicular phase is the major determinant of cycle length (Sherman BM, et al) Thismenstrual cycle change prior to menopause is marked by elevated follicle-stimulatinghormone (FSH) levels and decreased levels of inhibin, but normal levels of luteinizinghormone (LH) and slightly elevated levels of estradiol (Buckler HM, et al., 1991;MacNaughton J, et al., 1992; Hee J, et al., 1993; Burger HG, et al., 2000,2008). In the averagewoman, continuing follicular depletion and declining fertility begin at age 37–38, andmenopause follows approximately 13 years later (average age 51). However, inepidemiologic studies approximately 10% of women in the general population becomemenopausal by the age of 45, probably because they were born with a smaller than normalovarian follicular pool that is functionally depleted at an earlier age. Menopause occurswhen the number of remaining follicles falls below a critical threshold, about 1,000,regardless of age (Treloar AE, 1981).Recent longitudinal studies of women as they pass through the peri-menopausal transitionreveal that estrogen levels do not begin a major decline until about a year beforemenopause. (Burger HG, et al., 2008; Lasley BL, et al., 2002). Indeed, women experiencingthe peri-menopausal transition actually have higher overall estrogen levels, a response that
Reproductive Endocrinology Diseases: Hormone Replacement and Therapy for Peri/Menopause 275is logically explained by an increased ovarian follicular reaction to the increase in FSHsecretion during these years (Santoro N, et al). Variability in estrogen levels is characteristicof the peri-menopausal transition, with greater variability observed in menstrual cycles thatdisplay greater irregularity (Meyer PM, et al). As noted, most women experience a 2- to 8-year period of time prior to menopause when anovulation becomes common (Treloar AE, etal., 1996). During this period of time ovarian follicles continue their rate of loss untileventually the supply of follicles is finally depleted (Gougeon A, et al., 1994). The agerelatedchanges in the endocrine characteristics of the menstrual cycle that result fromprogressive follicular depletion correlate with a measurable decrease in ovarian volume andin the number of antral follicles observed by trans-vaginal ultrasonography during the earlyfollicular phase (Lass A, et al., 1997; Yong PY, et al., 2003; Frattarelli JL, et al., 2000; DumesicDA, et al., 2001; Bancsi LF, et al., 2002; Kupesic S, et., 2003). The inverse and tightrelationship between FSH and inhibin indicates that inhibin is a sensitive marker of ovarianfollicular competence and, in turn, that FSH measurement is a clinical assessment of inhibin(MacNaughton J, et al., 1992; Hee J, et al., 1993). The decrease in inhibin secretion by theovarian follicles begins early (around age 35), but accelerates after 40 years of age. This isreflected in the decrease in fecundity that occurs with aging. The major decrease in estradiollevels began about 2 years before menopause (Sowers MR, , et al., 2008). Declining levels ofinhibin-B and Anti-Müllerian Hormone (AMH) reached a low to non-detectable point about5 years before menopause (Sowers MR, et al., 2008).Although the inhibin-B and AMH results are in general agreement with other reports, theexactness of the timing is limited by the fact that the blood samples were obtained from only50 women in the study. Nevertheless, the Michigan study confirms the validity of AMH as amarker for the ovarian reserve of follicles. Unlike inhibin-B, AMH is not a participant in thefeedback relationship between the ovary and the pituitary gonadotropins, rather AMH, aproduct of granulosa cells, reflects the number of follicles present in the ovaries awaitingFSH stimulation (Visser JA, et al). The variability in these measurements from individual toindividual, however, precludes the practical use of these tests to predict with accuracy thefuture rate of menopause.The peri-menopausal years are a time period during whichpostmenopausal levels of FSH (greater than 20 IU/L) can be seen despite continuedmenstrual bleeding, while LH levels still remain in the normal range. Occasionally, corpusluteum formation and function occur, and the peri-menopausal woman is not safely beyondthe risk of an unplanned and unexpected pregnancy until elevated levels of both FSH (>20IU/L) and LH (>30 IU/L) can be demonstrated. The median age for the onset of thistransition was 47.5 years. Only 10% of women ceased men-struating abruptly with noperiod of prolonged irregularity. The peri-menopausal transition from reproductive to postreproductivestatus was, for most women, approximately 4 years in duration. In the studyby Treloar, the average age for entry into the peri-menopausal transition was 45.1, and theage range that included 95% of the women was 39–51 (Treloar AE, 1996). The mean durationof the peri-menopausal transition was 5.0 years, with a range of 2 to 8 years.5.1 Endocrine activity of the peri and post-menopausal ovaryAs reviewed above, mean estradiol levels are normal or high in peri-menopausal women,and FSH levels are often not suppressed despite these high estradiol levels. These aspects ofpituitary-ovarian relationships are contrary to expected physiology. It is proposed that,decreasing ovarian production of inhibin plays a role in the high average estrogen levelsdocumented during the peri-menopause. More specifically, the B subtype of inhibin, a small
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ARTIFICIAL INSEMINATION IN FARM ANIMALS - Phenix-Vet

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