Childhood conditions influence adult progesterone levels

Abstract

Background: Average profiles of salivary progesterone in women vary significantly at the inter- and intrapopulation level as a function of age and acute energetic conditions related to energy intake, energy expenditure, or a combination of both. In addition to acute stressors, baseline progesterone levels differ among populations. The causes of such chronic differences are not well understood, but it has been hypothesised that they may result from varying tempos of growth and maturation and, by implication, from diverse environmental conditions encountered during childhood and adolescence.

Methods and findings: To test this hypothesis, we conducted a migrant study among first- and second-generation Bangladeshi women aged 19-39 who migrated to London, UK at different points in the life-course, women still resident in Bangladesh, and women of European descent living in neighbourhoods similar to those of the migrants in London (total n = 227). Data collected included saliva samples for radioimmunoassay of progesterone, anthropometrics, and information from questionnaires on diet, lifestyle, and health. Results from multiple linear regression, controlled for anthropometric and reproductive variables, show that women who spend their childhood in conditions of low energy expenditure, stable energy intake, good sanitation, low immune challenges, and good health care in the UK have up to 103% higher levels of salivary progesterone and an earlier maturation than women who develop in less optimal conditions in Sylhet, Bangladesh (F9,178 = 5.05, p < 0.001, standard error of the mean = 0.32; adjusted R(2) = 0.16). Our results point to the period prior to puberty as a sensitive phase when changes in environmental conditions positively impact developmental tempos such as menarcheal age (F2,81 = 3.21, p = 0.03) and patterns of ovarian function as measured using salivary progesterone (F2,81 = 3.14, p = 0.04).

Conclusions: This research demonstrates that human females use an extended period of the life cycle prior to reproductive maturation to monitor their environment and to modulate reproductive steroid levels in accordance with projected conditions they might encounter as adults. Given the prolonged investment of human pregnancy and lactation, such plasticity (extending beyond any intrauterine programming) enables a more flexible and finely tuned adjustment to the potential constraints or opportunities of the later adult environment. This research is the first, to our knowledge, to demonstrate a postuterine developmental component to variation in reproductive steroid levels in women.

Figure 1. Average Luteal Progesterone Profiles by Group

Unadjusted mean luteal progesterone index values. Mean ± SEM: 22.2 ± 3.1 pg/ml (resident Bangladeshi sedentees from Sylhet [SYL], n = 39); 24.6 ± 2.5 pg/ml (adult migrants [ADU], n = 46); 38.9 ± 5.7 pg/ml (child migrants [CHI], n = 39); 40.2 ± 5.5 pg/ml (second-generation British-Bangladeshis [2ndGEN], n = 29); 45.1 ± 4.3 pg/ml (British women of European descent [WHI], n = 45). Sample sizes include only the cycles for which an oestradiol midcycle peak and luteal progesterone rise were discernable (81%, 82%, 93%, 88%, and 94% of the original sample for SYL, ADU, CHI, 2ndGEN, and WHI groups, respectively). Oestradiol values were obtained from data available for the same individual menstrual cycles. Ovulation dates were estimated from individual oestradiol data [22]. Confidence intervals are omitted for visual clarity. Sample sizes include all women for which hormonal data were available and may differ from total sample sizes for other aspects of data collection.

Figure 2. Average Luteal Progesterone Profiles by Categories of Age at Migration to the UK

Unadjusted mean luteal progesterone index values. Mean ± SEM: 44.3 ± 8.6 pg/ml (ages 0–8 y, n = 22); 31.8 ± 6.8 pg/ml (ages 9 y to menarche, n = 17); 24.6 ± 2.5 pg/ml (postmenarche, n = 46). Ovulation dates were estimated from oestradiol data available for the same individual menstrual cycles [22]. Confidence intervals are omitted for visual clarity. Sample sizes include all women for which hormonal data were available and may differ from total sample size for other aspects of data collection.