It has been hypothesized that, whenever estrogen levels decline, psychosis symptoms in women increase. At menopause, this can happen in two main ways: (a) the loss of estrogen (mainly estradiol) can directly affect central neurotransmission, leading to increase in schizophrenia-related symptoms, and (b) the loss of estrogen can decrease the synthesis of enzymes that metabolize antipsychotic drugs, thus weakening their efficacy. Aims and
Methods
The aim of this narrative review was to investigate the second possibility by searching PubMed and ClinicalTrials.gov for studies over the last two decades that investigated the metabolism of antipsychotics and their efficacy before and after menopause in women or that studied systemic and local estrogen level effects on the pharmacokinetics and pharmacodynamics of individual antipsychotic drugs.
Results
The evidence suggests that symptom level in women with schizophrenia rises after menopause for many reasons beyond hormones but, importantly, there is an estrogen-dependent loss of efficacy related to antipsychotic treatment.
Conclusion
Effective clinical intervention is challenging; nevertheless, several promising routes forward are suggested.
PMID 36291276 36291276 DOI 10.3390/brainsci12101342 10.3390/brainsci12101342 González-Rodríguez et al. 2022, González-Rodríguez 2022
Cite this article
González-Rodríguez, A., Monreal, J. A., & Seeman, M. V. (2022). The Effect of Menopause on Antipsychotic Response. Brain sciences, 12(10), 1342. https://doi.org/10.3390/brainsci12101342
González-Rodríguez A, Monreal JA, Seeman MV. The Effect of Menopause on Antipsychotic Response. Brain Sci. 2022;12(10):1342. doi:10.3390/brainsci12101342
González-Rodríguez, A., et al. "The Effect of Menopause on Antipsychotic Response." Brain sciences, vol. 12, no. 10, 2022, pp. 1342.
Doxycycline and other antibiotics have been implicated in oral contraceptive (OC) failure, but information is sparse and studies of a doxycycline-OC interaction are nonexistent. Because an interaction between doxycycline and OCs, especially those containing low-dose estrogen, could result in an unplanned and unwanted pregnancy, a controlled clinical trial of the effects of doxycycline on OC hormone concentrations was performed. Twenty-four women aged 18-35 years were recruited as volunteers from among the patients seen in a University-based family planning clinic. While they were on a steady dose of the OC Ortho-Novum 1/35, serum concentrations of ethinyl estradiol, norethindrone, and endogenous progesterone were measured on days 18, 19, and 20 of the menstrual cycle (control phase). These measurements were repeated on days 18, 19, and 20 of the following menstrual cycle while the patient was taking doxycycline, 100 mg twice daily (treatment phase). No statistically significant differences in serum levels of ethinyl estradiol, norethindrone, or endogenous progesterone were seen between the control and treatment phases. However, there was large inter-patient and intra-patient variability in ethinyl estradiol and norethindrone levels. No elevations of endogenous progesterone occurred to suggest ovulation during antibiotic administration in either phase. It is not known what effects longer or earlier administration of doxycycline during the OC cycle would have on serum hormone concentrations or ovulation. Pregnancies attributed to failure of OCs because of tetracycline use could in fact be due to other causes or could represent a true interaction that only manifests itself in a small proportion of women at risk.
menstrual-cycle/cycle-across-the-lifespan/cycle-and-general-healthreproductive-endocrinology/ovarian-hormones/estrogendiagnostics/hormone-testing/urinary-metabolites
Open Access
Bouchard TP et al., 2026·Journal of ovarian research
Reproductive hormones of the fertile window are often referenced to women in regular cycles, but this may not be representative of the hormonal profiles of women in different circumstances like polycystic ovarian syndrome, the postpartum period, and the perimenopause transition. This observational cohort study sought to identify the variability in the reproductive hormones in various clinical circumstances and to establish potential thresholds for each category based on hormone measurements with the Mira urinary hormone monitor. A total of 57 women (ages 22-51) in various circumstances (regular cycles, polycystic ovarian syndrome, postpartum and perimenopause) tracked Mira urine hormone measurements (estrone-3-glucuronide, luteinizing hormone, pregnanediol glucuronide), contributing 444 cycles of data. Using additive mixed models, hormone values were stratified by the four different reproductive categories. The perimenopause and polycystic ovarian syndrome groups demonstrated relative hypoestrogenic states, while the perimenopause group showed low luteal pregnanediol glucuronide and the polycystic ovarian syndrome/polyendocrine metabolic ovarian syndrome (PCOS/PMOS) group showed high luteal pregnanediol glucuronide. The perimenopause group had significantly higher luteinizing hormone values throughout the whole cycle. The fertile window hormone thresholds vary depending on a woman's specific reproductive category. Women in different circumstances should not necessarily use the same hormonal thresholds for the fertile window and ovulation. A larger dataset with ultrasound correlation to ovulation is required to delineate the fertile window with more precision. Hormone differences across the menstrual cycle could be used for targeted treatments in polycystic ovarian syndrome and perimenopause women.
Anti-Müllerian hormone (AMH), produced by ovarian granulosa cells, is a key regulator of female reproduction. Traditionally seen as a local follicular brake, emerging evidence calls for a paradigm shift. We propose that AMH acts as a context-dependent signaling hub. It primarily signals via the Smad1/5/8 pathway and interacts with Wnt/β-catenin and MAPK cascades to regulate follicle growth and steroidogenesis. Beyond the ovary, AMH and its receptors are expressed in the hypothalamus, pituitary, uterus, and placenta, modulating the hypothalamic-pituitary-gonadal axis and other reproductive processes. This review provides a comprehensive framework for understanding AMH as a context-dependent signaling hub in female mammals.
Sajjad MU et al., 2026·Archives of gynecology and obstetrics
The human placenta consumes, on average, one third of the glucose from maternal blood. However, the role of placental glucose consumption in the production of estradiol and progesterone remains unclear. We hypothesized that placental glucose consumption in humans is associated with steroid production via a non-glycolytic pathway. We included 41 healthy pregnancies at term. Blood samples were obtained from the maternal radial artery, uterine vein, and from the umbilical artery and vein during scheduled cesarean delivery. Blood flow in the uterine artery and umbilical vein was measured using Doppler ultrasound. Plasma concentrations of estradiol, progesterone, glucose, insulin, lactate, and ketones were analyzed. We calculated uteroplacental uptake and consumption of maternal glucose and ketones, and the loss of uteroplacental lactate in 6-carbon units as well as the release of steroid hormones into maternal circulation. Our data revealed a net placental release of estradiol and progesterone into maternal circulation [24.1 (5.34, 49.8) and 560.3 (61.2, 798.2) nmol/min, respectively]. The release of estradiol was positively associated with uteroplacental glucose uptake (ρ = 0.59, p < 0.001) and consumption (ρ = 0.43, p = 0.005), while progesterone exhibited similar associations (ρ = 0.61, p < 0.001; ρ = 0.43, p = 0.005). Notably, both hormones correlated positively with lactate-adjusted uteroplacental glucose consumption but not with acetate-equivalent uteroplacental ketone consumption. Placental release of estradiol and progesterone correlates with uteroplacental consumption of glucose that primarily occurs via non-glycolytic pathways in the third trimester placenta.