Substantial evidence now exists to indicate that the endogenous hypothalamic opioidergic mechanism(s) represents one of the important controlling systems for release of gonadotropin-releasing hormone. Modulations of frequency and amplitude of the secretory activity of gonadotropin-releasing hormone appears to be mediated through an inhibitory action of endogenous opioids, and the functional coupling of the opioidergic and gonadotropin-releasing hormone systems is an ovarian steroid-dependent event. There is also evidence to implicate suprahypothalamic mechanism(s) that enhance endogenous opioid inhibition of secretion of gonadotropin-releasing hormone. Although exogenous opioid peptides and their synthetic analogs consistently induce the secretion of prolactin, blockade of opioid receptors in humans by naloxone failed to elicit a decrement in the levels of prolactin under a variety of conditions. On the contrary, naloxone induced a remarkable increment in the secretion of prolactin via an increased frequency of pulsatile release which is synchronized with pulses of luteinizing hormone. These observations suggest that a common neuroendocrine mechanism is involved in the opioidergic control of the secretion of both luteinizing hormone and prolactin in women.
PMID 2990210 2990210 DOI 10.1016/s0002-9378(85)80162-9 10.1016/s0002-9378(85)80162-9
Cite this article
Yen, S. S., Quigley, M. E., Reid, R. L., Ropert, J. F., & Cetel, N. S. (1985). Neuroendocrinology of opioid peptides and their role in the control of gonadotropin and prolactin secretion. American journal of obstetrics and gynecology, 152(4), 485-493. https://doi.org/10.1016/s0002-9378(85)80162-9
Yen SS, Quigley ME, Reid RL, Ropert JF, Cetel NS. Neuroendocrinology of opioid peptides and their role in the control of gonadotropin and prolactin secretion. Am J Obstet Gynecol. 1985;152(4):485-493. doi:10.1016/s0002-9378(85)80162-9
Yen, S. S., et al. "Neuroendocrinology of opioid peptides and their role in the control of gonadotropin and prolactin secretion." American journal of obstetrics and gynecology, vol. 152, no. 4, 1985, pp. 485-493.
Reproductive function in humans changes markedly during life and is usually divided into four stages. During the initial stage, which begins early in fetal life and ends in infancy, gonadotropins and gonadal steroids are secreted at levels similar to those seen in early and mid-adolescence. In the second stage, which lasts from infancy through the first decade of life, reproductive function first regresses and then becomes quiescent. Puberty, the third stage, is heralded by a nocturnal increase in the secretion of gonadotropins and sex steroids. This nocturnal predominance gradually diminishes and disappears during the fourth stage — adulthood. In men, . . .
To examine the site of action of clomiphene citrate (CC), LH and FSH pulsatile amplitude, frequency, and responsiveness to GnRH (10 micrograms, iv) were studied in 11 women during the early follicular phase of the menstrual cycle. Six women received CC (150 mg/day) on cycle days 2, 3, and 4, while 5 women received placebo tablets. Blood samples were drawn at 10-min intervals for 8 h before and after the treatment regimen on cycle days 2 and 5, respectively. All women treated with CC had multiple follicular development, as determined by ultrasound. Peripheral levels of estradiol did not change after CC treatment, while progesterone levels decreased slightly. Mean levels of LH increased from 7.5 +/- 0.9 (+/- SEM) to 10.7 +/- 1.4 mIU/ml (P less than 0.05), and FSH increased from 6.7 +/- 0.9 to 10.1 +/- 0.9 mIU/ml (P less than 0.01). After exposure to CC, the pulse frequency of LH during an 8-h period increased significantly (3.3 +/- 0.7 on day 2 vs. 6.8 +/- 0.8 on day 5; P less than 0.01), while the pulse frequency of FSH increased from 3.8 +/- 0.6 to 5 +/- 1.4, as determined by computer pulse analyses. The pulse amplitude of LH and FSH was not significantly altered. In the placebo-treated group, neither pulse amplitude nor pulse frequency changed significantly between cycle days 2 and 5. Pituitary sensitivity to exogenous GnRH did not change after CC treatment. Since the pulsatile frequency of LH is governed by hypothalamic influences, these findings provide compelling evidence for a hypothalamic site of action for CC, probably by inducing an increase in the frequency of GnRH secretion.
EndometriosisAMH and Ovarian ReserveSurgical Staging and TypologyAnti-Müllerian Hormone
Endometriosis is a chronic, gynecologic condition in which tissue similar to the lining of the uterus implants throughout the body. Women with endometriosis have a higher prevalence of infertility and a greater risk of early natural menopause compared to those without endometriosis. This study aimed to evaluate preoperative serum AMH levels among women with and without incident endometriosis and to assess whether levels differ by surgical staging and typology. The ENDO (Endometriosis: Natural History, Diagnosis, and Outcomes) study was conducted between 2007 and 2009. The ENDO study consisted of an operative and population cohort (n=600). Only those in the ENDO operative cohort from the Utah site were used for this analysis, and included women aged 18 to 44 years who were scheduled for gynecologic surgery, irrespective of clinical indication (n=476). AMH levels were measured from stored serum collected before surgery using a quantitative enzyme-linked immunosorbent assay. After excluding participants with missing outcome data (n=51), unilateral oophorectomy (n=8), or those within the population cohort (n=69), 348 participants remained for the analysis. Surgically confirmed endometriosis diagnosis, staging (American Society for Reproductive Medicine I-IV), and typology (superficial, deep, ovarian) were ascertained by the operative report. Outliers for AMH (>14.0 ng/mL) were excluded from the analyses and AMH values were log-transformed. Multivariable linear regression models adjusted for age (squared and continuous), body mass index, serum cotinine levels, and exogenous hormonal contraceptive use were conducted. Percentage differences in AMH were calculated as (exp[β]-1)×100, and 95% confidence intervals were reported. Compared with no endometriosis, incident endometriosis diagnosis was associated with lower AMH levels (-19.8%; 95% confidence interval, -37.0 to 1.0); however, this association was not statistically significant. Stage III to IV disease was associated with 40.1% lower AMH levels (95% confidence interval, -58.9 to -12.7). Ovarian endometriomas were most strongly associated with lower AMH levels (-54.3%; 95% confidence interval, -69.4 to -31.8), with a more pronounced association among those with infertility (-72.6%; 95% confidence interval, -85.4 to -48.5). Deep (-24.1%; 95% confidence interval, -48.2 to 11.0) and superficial (-15.5%; 95% confidence interval, -34.6 to 9.3) endometriosis also showed a trend toward lower AMH levels, but these findings were not statistically significant. Compared with a postoperative diagnosis of a normal pelvis, incident endometriosis was associated with 26.8% lower AMH levels (95% confidence interval, -44.6 to -3.4). Stage III to IV disease was associated with 47.8% lower AMH levels (95% confidence interval, -65.8 to -23.2), and all subtypes of endometriosis were statistically significantly associated with lower levels of AMH compared with a postoperative diagnosis of a normal pelvis (ovarian: -60.8%; 95% confidence interval, -74.4 to -39.9; -34.3%; 95% confidence interval, -56.2 to -1.4; -24.8%; 95% confidence interval, -43.9 to -0.8). Ovarian and moderate to severe (stage III-IV) endometriosis were associated with markedly lower AMH levels compared with no endometriosis. Compared with a postoperative diagnosis of a normal pelvis, incident endometriosis and moderate to severe stages (stage III-IV) were associated with statistically significantly lower AMH levels. Additionally, typology (deep, ovarian, or superficial) was associated with statistically significantly lower AMH levels. However, this association was likely driven by the presence of ovarian endometriomas across all subtypes. These findings are consistent with previous studies and demonstrate that endometriosis lesions themselves, independent of surgical intervention, influence AMH levels.
General OB/GYNUterine Closure TechniqueHysterotomy RepairCesarean Scar Complications
Bujold E et al., 2026·American Journal of Obstetrics and Gynecology
Normal uterine function depends on cyclical regeneration and the capacity to sustain pregnancy. A cesarean incision represents an injury to this remarkable organ. Although the uterus possesses exceptional healing potential, cesarean delivery increases the risk of secondary infertility, pelvic pain, uterine rupture, and abnormal placentation in subsequent pregnancies. The two most important determinants of successful hysterotomy healing after cesarean delivery are the location of the incision and the surgical technique used for closure. The anatomic site of entry-whether the corpus, lower uterine segment, or cervix-defines the tissue composition, vascularity, and contractility at the wound margins, which in turn influence how the scar remodels and withstands subsequent pregnancies. Surgical technique is also important. A robust body of experimental and clinical evidence demonstrates that restoring anatomic integrity by reapproximating uterine layers while excluding the endometrium produces stronger scars and reduces late complications. The rationale for excluding the endometrium is to prevent displacement of endometrial tissue into the myometrium and to avoid mucosal tearing against a foreign body (i.e. suture material), both of which predispose to defective healing. When the endometrium is incorporated, healing is often impaired, leading to niches or isthmoceles, adenomyosis, and endometriosis at the scar site. Over time, these defects have been recognized as contributors to abnormal bleeding, pelvic pain, infertility, uterine rupture, and placenta accreta spectrum disorders. Despite this evidence, single-layer closures that incorporate endometrium became widely adopted because of their speed and simplicity, while their long-term sequels were initially underappreciated. This has prompted renewed scrutiny of closure techniques, including comparisons of single-layer vs double-layer closure, locking vs nonlocking sutures, type of sutures, and the direction of suture. Collectively, the data show that optimal closure respects uterine anatomy, restores the natural alignment of tissues, and achieves hemostasis without compromising perfusion or strangulating tissues. Building on these principles, we herein describe a refined 3-layer closure. The first layer approximates decidua and junctional myometrium while excluding surface endometrium to prevent tissue entrapment and bacterial contamination. The second layer restores anatomic wall integrity by reapproximating the bulk of the myometrium, thereby reinforcing strength and distributing tension across the scar. The third layer reapproximates superficial myometrium and serosa, smoothing the uterine surface and reducing adhesions. This technique is not simply a return to traditional double-layer methods or an extension of single-layer practice, but rather a refinement that integrates lessons from visceral surgery and contemporary obstetric data. Its rationale is to restore anatomy, secure hemostasis without ischemia, and preserve long-term uterine function. While short-term safety appears comparable across closure methods, evidence increasingly indicates that long-term reproductive outcomes depend on how closure respects tissue biology. We argue that appropriate repair is more meticulous restoration of uterine anatomy should take precedence over operative speed. The enduring success of a hysterotomy repair depends on the surgical technique employed, as it directly affects women's future reproductive health.