LONG-TERM EFFECTS OF A 1ST PREGNANCY ON THE HORMONAL ENVIRONMENT - ESTROGENS AND ANDROGENS
LONG-TERM EFFECTS OF A 1ST PREGNANCY ON THE HORMONAL ENVIRONMENT - ESTROGENS AND ANDROGENS
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DOI：
10.1210/jcem-64-1-111
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发表时间：
1987-01-01
影响因子：
5.8
通讯作者：
PREEDY, JRK
中科院分区：
文献类型：
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作者：
MUSEY, VC;COLLINS, DC;PREEDY, JRK
早期（但不是晚期）的第一次怀孕已知对乳腺癌有保护作用。这种影响可能是通过第一次怀孕早期引起的激素环境的长期变化来介导的。为了研究这种变化的可能性，我们对四组妇女的血清和尿雌激素和血清雄激素进行了前瞻性纵向研究，即早期（年龄，18-23岁）首次妊娠（n=15），早期对照（n=20），晚期（年龄，29-40岁）首次妊娠（n=9）和晚期对照（n=20）。在首次妊娠前（初次访视）和首次妊娠后7-19个月（回访）对妊娠组进行研究。对照组进行了类似的研究，但没有干预怀孕。测定了以下指标：血清雌酮（E1）、17 β-雌二醇（E1）、雌二醇（E2）、雌三醇（E3）和硫酸雌二醇（E1）;这三种雌激素的尿总E1、E2、E3和葡糖苷酸;以及血清睾酮、硫酸脱氢表雄酮（DHAS）和脱氢表雄酮（DHA）。在妊娠组或相应的对照组中，血清E1、E2、E1硫酸盐或任何尿雌激素在初始和回访之间均无显著变化。然而，与对照值相比，两个妊娠组的初始和回访之间的血清E3显著增加。血清睾酮无明显变化。与相应的对照组值相比，两个妊娠组的初始和回访之间的血清DHAS和DHA均显著降低。两个妊娠组的血清E3与DNA比值也显著增加。然后在一系列经产和未经产妇女中进行横断面研究（仅测量血清DHAS和DHA）。血清DHAS和DHA水平显着和显着低于初产妇，如预期的。在血清DHAS或DHA水平与上次分娩后的月数（最多150个月）之间没有显著的关系，表明这些变化至少持续了这段时间。血清DHAS或DHA水平与产次（以前怀孕1 - 3次）之间没有显着关系，表明这种变化仅发生在第一次怀孕后。我们的结论是：1）首次妊娠引起了一个长期的内分泌环境的变化，血清E3显著升高，血清DHAS和DHA显著降低，2）这些变化发生在早期和晚期的首次妊娠;（3）产后血清E_3至少19个月，（12-13岁）分娩后的血清DHAS和DHA;和4）的影响只发生在第一次怀孕后，而不是在随后的怀孕。这些长期的激素变化可能是乳腺癌保护机制的一部分，与早期的第一次怀孕有关。由于这种变化发生在第一次怀孕的早期和晚期，因此其影响可能取决于暴露的持续时间，而不是变化本身。
An early (but not a late) first pregnancy is known to be protective for breast cancer. This effect might be mediated through a long term change in the hormonal environment caused by the early first pregnancy. To investigate the possibility of such a change we carried out a prospective longitudinal study of serum and urinary estrogens and serum androgens in four groups of women, namely early (age, 18-23 yr) first pregnancy (n=15), early control (n=20), late (age, 29-40 yr) first pregnancy (n=9), and late control (n=20). The pregnancy groups were studied before (initial visit) and 7-19 months after a first pregnancy (return visit). The control groups were similarly studied, but without an intervening pregnancy. The following were measured: serum estrone (E1), 17.beta.-estradiol (E2), estriol (E3), and E1 sulfate; urinary total E1, E2, E3, and glucosiduronates of these three estrogens; and serum testosterone, dehydroepiandrosterone sulfate (DHAS), and dehydroepiandrosterone (DHA). There was no significant change between the initial and return visits in serum E1, E2, E1 sulfate, or any of the urinary estrogens in either pregnancy group or in the corresponding control groups. There was, however, a significant increase in serum E3 between initial and return visits for both pregnancy groups compared with the control values. There was no significant change in serum testosterone. There was a marked significant decrease in both serum DHAS and DHA between initial and return visits in both pregnancy groups compared with the corresponding control group values. There was also a significant increase in the serum E3 to DNA ratio in both pregnancy groups. A cross-sectional study (measuring serum DHAS and DHA only) was then carried out in a series of parous and nulliparous women. The serum DHAS and DHA levels were markedly and significantly lower in parous than in nulliparous women, as expected. There was no significant relationship beween serum DHAS or DHA levels and months elapsed (up to 150) since last delivery, indicating that the changes last at least for this period of time. There was no significant relationship between serum DHAS or DHA levels and parity (one to three previous pregnancies), indicating that the changes occur only after a first pregnancy. We conclude that 1) a first pregnancy induces a long termalteration in the hormonal environment in respect to serum E3, which increases significantly, and serum DHAS and DHA, which decrease significantly; 2) these changes occur with both an early and a late first pregnancy; 3) the duration of the efect is at least 19 months after delivery for serum E3 and at least 150 months (12-13 yr) after delivery for serum DHAS and DHA; and 4) the effect occurs only after a first pregnancy and not after succeeding pregnancies. These long term hormonal changes may form part of a protective mechanism for breast cancer, associated with an early first pregnancy. Since the change occurs after both early and late first pregnancy, the effect may be dependent on the duration of exposure rather than to the change itself.