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Characteristics of reproductive life and risk of breast cancer in a case-control study of young nulliparous women
Abstract
Between 1982 and 1985, a case-control study of nulliparous women, aged 25-45, was conducted to analyse the relationships between the risk of breast cancer and causes of nulliparity, including contraceptive methods. Fifty-one cases of breast cancer diagnosed less than 3 months before interview were matched with 95 controls on age at diagnosis, year of interview, and medical center. The causes of nulliparity related to female sterility or subfertility (mechanical or hormonal disorders) were not found to be associated with a significantly higher risk of breast cancer. The causes related to fertilization failure, i.e. no sexual partner, rare sexual intercourse (less than once per month), or partner with abnormal semen, were found to lead to an increased risk. Detailed analysis of contraceptive methods showed that the risk of breast cancer increased (p = 0.02) with a longer duration of use of barrier methods (withdrawal or condom). Conversely, the risk significantly decreased (p = 0.004) with a longer duration of use of non-barrier methods (oral contraceptives, IUD, cap, local spermicides, vaginal douche, safe period, or no method), i.e. methods allowing a direct exposure to human semen.
... Childbearing and breastfeeding, where OT plays a crucial role, are known protective factors against breast cancer [23,24]. Childless women (the nulliparous populations) have a higher risk for breast cancer development than those who have given birth to one or more children [41][42][43]. Prolonged breastfeeding, usually involving multiple children, correlates with a progressive decrease in breast cancer risk [23,44,45]. In the collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50,302 women with and 96,973 women without breast cancer, the relative risk to develop the disease decreased by 4% for every 12 months of breastfeeding, and by 7% for each birth in women who never breastfed [24]. ...
... The 'non-sexual' breast may carry a breast cancer risk similar to that of the 'nonbreastfeeding' breast [47]. In age-matched nulliparous women, breast cancer incidence was lower in the sexually active group than in the celibate group [43], which also aligns with increased OT plasma levels in sexually aroused women [48]. ...
Breast cancer is making up one-quarter of all new female cancer cases diagnosed worldwide. Breast cancer surgeries, radiation therapies, cytotoxic chemotherapies and targeted therapies have made significant progress and play a dominant role in breast cancer patient management. However, many challenges remain, including resistance to systemic therapies, tumour recurrence and metastasis. The cyclic neuropeptide oxytocin (OT) elicits a plethora of biological responses via the oxytocin receptor (OTR) in both the central and peripheral nervous system, including social bonding, stress, maternal behaviour, sexual activity, uterus contraction, milk ejection and cancer. As a typical member of the G protein-coupled receptor family, OTR represents also an intriguing target for cancer therapy. There is emerging evidence that OTR plays a role in breast cancer development and progression, and several breast cancer cell lines express OTR. However, despite supporting evidence that OT lowers breast cancer risks, its mechanistic role in breast cancer development and the related signalling pathways are not fully understood. Here, we review the current knowledge of the OT/OTR signalling system in healthy breast tissue as well as in breast cancer, and discuss OTR as a potential therapeutic target for breast cancer management.
... Engaging in sexual activity has been shown to have benefits for older adults' mental and physical health and wellbeing. Studies have shown that a higher frequency of sexual activity is associated with a reduction in cardiovascular events in later life, reduced risk of fatal coronary events, prostate and breast cancer, and better reported quality of life (Bosland, 1988;Ebrahim et al., 2002;Flynn & Gow, 2015;Lê, Bachelot, & Hill, 1989;Liu, Waite, Shen, & Wang, 2016). However, despite the health benefits of engaging in sexual activity in later life, when individuals are at the greatest risk of developing chronic diseases, there tends to be a decline in sexual activity with age. ...
... Alternatively, it is possible that individuals who drink may be more sociable and also more likely to go out than their nondrinking counterparts; sociability may increase the odds of meeting a partner and, subsequently, having sexual interactions. Sexual activity has been shown to be beneficial for physical and mental health (Lê et al., 1989;Liu et al., 2016) but declines in older age (Lee et al., 2015). Interestingly, the present results suggest that regular alcohol use and binge drinking might protect against this age-related decline. ...
The present study aimed to investigate associations between alcohol consumption, including binge drinking, and sexual activity. Data were from 1,622 men and 2,195 women aged ≥50 years participating in the English Longitudinal Study of Ageing. Multivariable logistic regression was used to prospectively assess sex-specific associations between baseline frequency of alcohol use in the last year or binge drinking in the last week (self-reported in 2004/05) and sexual activity at 8-year follow-up (2012/13). Covariates included partner status, age, ethnicity, wealth, limiting long-standing illness, smoking status, physical activity, and depressive symptoms. After adjustment, regular alcohol consumption in the last year at baseline was associated with 111% higher odds (95% CI 1.36-3.27) of any past-year sexual activity at follow-up in men and 76% higher odds (95% CI 1.26-2.46) in women, while frequent alcohol consumption was associated with 175% higher odds (95% CI 1.75-4.32) of sexual activity in men and 100% higher odds (95% CI 1.38-2.89) in women, relative to drinking alcohol never or rarely. Binge drinking was also positively associated with sexual activity at follow-up after adjustment for covariates, with odds of being sexually active at follow-up 52% higher (95% CI 1.07-2.15) among men who reported binge drinking at baseline and 57% higher (95% CI 1.11-2.23) among female binge drinkers. These results suggest that regular, frequent or binge drinking may protect against a decline in sexual activity as people grow old. While this does not outweigh the health risks associated with excessive alcohol consumption, health practitioners should consider the association between alcohol use and sexual activity when screening older adults for alcohol use and when encouraging older adults to reduce their alcohol consumption.
... 13 With respect to the frequency of sexual activity, studies have shown higher sexual activity was linked to lower physical health. 14e16 Nevertheless, frequent sexual intercourse has been associated with reduced risk of fatal coronary events and breast cancer 17,18 and with greater enjoyment of life, 19 quality of life, 20 well-being, 21 and cognitive function, 22,23 suggesting a protective effect of sexual activity. ...
Background
Sexual activity can be referred to as a health behavior and may also act as an indicator of health status.
Aim
To evaluate temporal trends in sexual activity and to examine associations of sexual activity with all-cause and cause-specific mortality risk.
Methods
We examined the trends and prevalence of sexual activity and association of sexual activity with all-cause and cause-specific mortality in a nationally representative sample using data from the US National Health and Nutrition Examination Survey from 2005 to 2016 and the National Health and Nutrition Examination Survey 2005-2014 Linked Mortality File (through December 31, 2015).
Outcomes
All-cause, cardiovascular disease, and cancer mortality.
Results
A total of 15,269 US adults (mean age, 39.1 years [standard error, 0.18 years]) were included in the trend analysis. In the 2015-2016 cycle, while 71.7% (95% CI, 67.7–75.7%) US adults aged 20-59 years engaged in sexual activity ≥ 12 times/year (monthly), only 36.1% (95% CI, 31.6–40.7%) of them engaged in sexual activity ≥ 52 times/year (weekly). Since the 2005–2006 cycle, the estimated prevalence of sexual activity, ≥52 times/year and ≥12 times/year, were both stable over time among overall and each age group (all P for trend >0.1). During a median follow-up of 5.7 years (range, 1–11 years) and 71,960 person-years of observation, among 12,598 participants with eligible information on mortality status, 228 deaths occurred, including 29 associated with cardiovascular disease and 62 associated with cancer. Overall, participants with higher sexual activity frequency were at a lower risk of all-cause death in a dose-response manner (P for trend = 0.020) during the follow-up period. In addition, the multivariable-adjusted hazard ratios for all-cause mortality, CVD mortality, cancer mortality, and other cause mortality among participants who had sex ≥52 times/year compared with those having sex 0–1 time/year were 0.51 (95% CI, 0.34 to 0.76), 0.79 (95% CI, 0.19 to 3.21), 0.31 (95% CI, 0.11 to 0.84), and 0.52 (95% CI, 0.28 to 0.96), respectively.
Clinical Implications
Sexual activity appears to be a health indicator of all-cause and cancer mortality in US middle-aged adults.
Strengths & Limitations
Clear strengths of the present study include the large representative sample of the noninstitutionalized US population as well as the identification of precise estimates in relation to sexual activity and mortality. However, because of the observational nature of the study design, causality could not be determined.
Conclusions
Sexual activity was found to be associated with a lower risk of mortality from all cause and cancer.
Cao C, Yang L, Xu T, et al. Trends in Sexual Activity and Associations With All-Cause and Cause-Specific Mortality Among US Adults. J Sex Med 2020;XX:XXX–XXX.
... Frequency of sexual intercourse has also been shown to be associated with reduced risk of fatal coronary events, and prostate and breast cancer in studies using a longitudinal or casecontrol designs. [6,7] Several other studies have shown an association between sexual activity and physical health, for example see [8][9][10]. In relation to mental health, frequent sexual activity has been shown to be associated with greater enjoyment of life [11], quality of life [12], wellbeing [13], and cognitive function. ...
Background
On 23rd March 2020 the UK government released self-isolation guidance to reduce the risk of transmission of SARS-Cov-2. The influence such guidance has on sexual activity is not known.
Aim
To investigate levels and correlates of sexual activity during COVID-19 self-isolation in a sample of the UK public.
Methods
This paper presents pre-planned interim analyses of data from a cross-sectional epidemiological study, administered through an online survey.
Outcomes
Sexual activity was measured using the following question: “On average after self-isolating how many times have you engaged in sexual activity weekly?” Demographic and clinical data was collected, including sex, age, marital status, employment, annual household income, region, current smoking status, current alcohol consumption, number of chronic physical conditions, number of chronic psychiatric conditions, any physical symptom experienced during self-isolation, and number of days of self-isolation. The association between several factors (independent variables) and sexual activity (dependent variable) was studied using a multivariable logistic regression model.
Results
868 individuals were included in this study. There were 63.1% of women, and 21.8% of adults who were aged between 25 and 34 years. During self-isolation, 39.9% of the population reported engaging in sexual activity at least once per week. Variables significantly associated with sexual activity (dependent variable) were being male, a younger age, being married or in a domestic partnership, consuming alcohol, and a higher number of days of self-isolation/social distancing.
Clinical Implications
In this sample of 868 UK adults self-isolating owing to the COVID-19 pandemic the prevalence of sexual activity was lower than 40%. Those reporting particularly low levels of sexual activity included females, older adults, those not married, and those who abstain from alcohol consumption.
Strength and Limitations
This is the first study to investigate sexual activity during the UK COVID-19 self-isolation/social distancing. Participants were asked to self-report their sexual activity potentially introducing self-reporting bias into the findings. Second, analyses were cross-sectional and thus it is not possible to determine trajectories of sexual activity during the current pandemic.
Conclusion
Interventions to promote health and wellbeing during the COVID-19 pandemic should consider positive sexual health messages in mitigating the detrimental health consequences in relation to self-isolation and should target those with the lowest levels of sexual activity.
... For example, in a US-based study of 1046 men and 1158 women (aged 57-85), with a 5-year follow-up, frequent and high-quality sex was found to protect against cardiovascular events in later life [2]. Regular sexual activity has also been shown to be associated with reduced risk of fatal coronary events, as well as prostate and breast cancer [3][4][5]. Moreover, engaging in sexual activity has been shown to be beneficial for mental health. ...
Sexual activity is a central component of intimate relationships and has been shown to have numerous benefits for health and wellbeing. Studies have shown that people with disabilities often report less satisfaction with their sex lives, but none have examined the levels of sexual activity in older adults with visual problems. We investigated associations between self-rated eyesight and sexual activity in a population-based sample of older adults. Analyses were conducted using data from 2587 men and 3238 women participating in the English Longitudinal Study of Ageing. Participants provided information on self-rated eyesight in three domains: overall, at distance, and up close (categorised as: excellent/very good/good/fair–poor), sexual activity (any vs. none in the last year), and frequency of sexual intercourse in the last month (not at all, once, 2–3 times, once a week or more) among those who were sexually active. Associations between self-rated eyesight and sexual activity were examined using adjusted logistic regression. Relative to excellent self-rated eyesight, fair–poor eyesight was consistently associated with significantly lower odds of being sexually active in men (overall eyesight OR 0.41, 95% CI 0.26–0.64, p < 0.001) but not in women (overall eyesight OR = 0.99, 95% CI 0.70–1.41, p = 0.959). However, among women who were sexually active, there was some evidence that fair–poor eyesight was associated with lower frequency of sexual intercourse in the last month (e.g. fair–poor eyesight at distance OR = 0.45, 95% CI 0.31–0.66, p < 0.001). No association between self-rated eyesight and frequency of sexual intercourse was observed for men. Identifying ways to help older patients with impaired vision achieve a more active sex life could help to improve the health and wellbeing of this population group. Visual impairment is associated with lower prevalence of any sexual activity in older men, and lower frequency of sexual intercourse in older women.
... [8] A growing literature has documented associations between engaging in sexual activity and better health and wellbeing. Studies have shown that a higher frequency of sexual activity is associated with a number of benefits for physical and mental health, including a reduction in cardiovascular events in later life, reduced risk of fatal coronary events, prostate and breast cancer, [9][10][11] and better reported quality of life. [12] While the cross-sectional design employed by the majority of these studies means it is not clear whether sexual activity promotes good mental and physical health or whether good mental and physical health promotes a higher frequency of sexual activity (or indeed, whether the relationship is bidirectional), there are plausible mechanisms by which sexual activity may be beneficial for health and wellbeing. ...
Objective
To investigate the association between weight status and sexual activity in middle-aged and older adults.
Methods
Cross-sectional analysis on Wave 6 (2012/13) of the English Longitudinal Study of Ageing. Data were from 2,200 men and 2,737 women aged ≥50 years (mean 68.2 years). The explanatory variable was weight status, defined as normal-weight (BMI: ≤24.9), overweight (BMI: 25.0–29.9) or obese (BMI: ≥30) based on objective measurements of height and weight. Outcome variables were any self-reported sexual activity in the last year (yes/no) and, if yes, frequency of sexual intercourse in the last month. Covariates included a range of sociodemographic, lifestyle, and health-related variables. Associations were analysed using binary (past-year sexual activity) and ordinal (frequency of past-month sexual intercourse) logistic regression models.
Results
The majority (73.3%) of men and half (50.0%) of women reported any sexual activity in the last year. The odds of reporting any sexual activity in the last year did not differ significantly by weight status in either men or women. However, among those who were sexually active, men with overweight (OR = 1.45, 95% CI 1.15–1.81, p = 0.002) or obesity (OR = 1.38, 95% CI 1.07–1.77, p = 0.015), and women with overweight (OR = 1.34, 95% CI 1.05–1.71, p = 0.017) reported significantly more frequent sexual intercourse in the last month compared with those who had a BMI in the normal-weight range, after adjustment for covariates.
Conclusion
Older adults with overweight or obesity who are sexually active engage in more frequent sexual activity than those who are normal weight.
Sexuality remains an essential aspect of life in older adults and substantially contributes to health outcomes. It is important for healthcare workers to be aware of challenges older adults face in the context of sexuality, to consider possible barriers, and to adequately address issues concerning sexuality when working with older adults. This chapter addresses some of the issues that healthcare workers face in the context of sexuality in older adults and to provide guidance on how to approach them. Barriers to communication often include common misconceptions, such as “older adults do not engage in sex”, “sex is defined as penile-vaginal intercourse”, “orgasm is the only goal of sex”, and “risk of sexually transmitted infections and HIV among older populations is low” and healthcare workers’ awareness of their own knowledge and experience with the subject are discussed. Tools including an evaluation of sexual health services, practical communication tools, and ways to initiate a conversation on sexuality are provided. Guidelines on sexual history taking, an important part of an exam for the patient’s health including sexual orientation, gender identity, sexual activities, potential risk behavior, romantic and sexual partner(s), and signs or symptoms of sexual problems or dysfunctions, are presented.
Introduction
Recent studies have reported that the quarantine imposed in several countries around the world due to Covid-19 affected the sexual function and relationship quality. On the March 23, 2020 the Greek government imposed a national quarantine to contain the spread of the pandemic. The impact of such conditions on sexual function and relationship quality of couples is unknown.
Aim
To investigate sexual function and relationship quality of couples during the quarantine.
Methods
An online anonymous survey was conducted one month post-impose of the quarantine, between the April 21 and the May 3, 2020. Adult respondents in a relationship completed a questionnaire including sociodemographic characteristics, structured inquiries regarding sexual activity and quality of relationship, anxiety level, and mood during the quarantine, as well as the IIEF and FSFI indices.
Outcomes
Sexual function was assessed using the Greek versions of the FSFI and IIEF for females and males respectively. Sexual activity using 5 statements regarding frequency of sexual thoughts, masturbation, and intercourse, quality of intercourse and general estimation of the level of sexual function. Participants graded their level of agreement. Relationship quality was assessed using 5 questions regarding communication, company, understanding, tension and general estimation of companionship. Participants graded their level of agreement. Two additional statements were used in order to evaluate mood and the level of anxiety.
Results
A sum of 299 adult heterosexual participants in a relationship participated. Little or no negative impact on sexual function was reported. Increased anxiety and deficient mood were reported only for those with no access to their partner. Being in a steady relationship and living with their partner, but only for couples without children, resulted in satisfaction by sexual activity and enhanced emotional security.
Conclusion
Sexual function and relationship quality appeared as not affected by the quarantine and by the measures of social distancing. Sotiropoulou P, Ferenidou F, Owens D, et al. The Impact of Social Distancing Measures Due to COVID-19 Pandemic on Sexual Function and Relationship Quality of Couples in Greece. Sex Med 2021;XX:XXXXXX.
Introduction: Numerous epidemiological studies performed throughout the world have confirmed the role of many risk factors. However, evidence suggests that international variation in the burden of breast cancer reflects differences in the patterns of risk factors. Hence this study is undertaken to assess the risk factors associate with breast cancer in a district in Karnataka. Method: This is a Case control study to assess the risk factors associated with breast cancer among cases attending radiation unit of Hassan institute of medical sciences during 2019. Results: There was a significant association of breast cancer with menarche attained at or less than age 13 years (OR=2.43, CI: 1.09-5.4, p<0.029), usage of oral contraceptive (OR=2.04: CI 1.61-2.42; p<0.1), and menopause attained before age 50 (OR=5.2: CI2.2-12.2; p<0.00). Our study also found that for every year increase in age for 1st birth, controls not being diseased decreased by 26% was statistically significant (OR=0.76; CI:0.61-0.89; p<0.002) and for every parity added, controls not being deceased increased by 1.13 time (OR=1.13; CI:0.69-1.8;p<0.6). Conclusion: District cancer control programme should advice women, to consume non-vegetarian food in moderation, promote physical activity form early age to maintain ideal body mass index.
Introduction
Physical activity is likely to be associated with sexual activity. However, to date, there is no literature on the relationship between overweight/obesity and sexual activity outcomes.
Aim
Thus, the present study assessed the associations among physical activity, sedentary behavior, and weight status with sexual activity and number of previous sexual partners in a representative sample of U.S. adults.
Methods
Data on leisure time physical activity, total sitting time, weight status, sexual behavior outcomes, and other characteristics were extracted from the National Health and Nutrition Study cycle 2007 to 2016. Logistic regression models were used to evaluate associations among body mass index, leisure time physical activity, and total sitting time with past-year sexual activity and number of sexual partners.
Main Outcome Measure
Self reported frequency of past-year sexual activity and number of sex partners in the past year.
Results
In a sample of 7,049 men (mean age: 38.3 ± 0.3 years) and 7,005 women (mean age: 38.7 ± 0.2 years) being overweight was associated with higher odds of frequent sexual activity (OR = 1.5; 95% CI = 1.2−1.7) among men, but lower odds among women (OR = 0.8; 95% CI = 0.6−0.9). Sufficient physical activity was associated with higher odds of frequent sexual activity among both men (OR = 1.3; 95% CI = 1.1−1.5) and women (OR = 1.2; 95% CI = 1.0−1.4). In those living alone, being obese was associated with lower odds of having at least 1 sexual partner for men (OR = 0.7; 95% CI = 0.5−0.9) and women (OR = 0.6; 95% CI = 0.4−0.8). Being sufficiently physically active was associated with higher odds of having at least 1 sexual partner only in men (OR = 1.6; 95% CI = 1.2−2.2).
Clinical Implications
Healthcare professionals need to be made aware of these results, as they could be used to plan tailored interventions.
Strengths & Limitations
Strengths include the large, representative sample of U.S. adults and objective measures of anthropometry. Limitations include the cross-sectional design of the study and that all variables on sexual history were self-reported.
Conclusion
The present study identifies novel modifiable behavioral and biological antecedents of sexuality outcomes.
There is no significant difference in the frequency of breast cancer in childless women who are either single or married. Nulliparous ever-married women have no less breast cancer than nulliparous single women. The highest frequency of breast cancer was found in nulliparous women, with decreasing frequency of the disease as the number of pregnancies increased. The genetic or familial factors presumably present in some of the close relatives of women with breast cancer appear to be as potent as the parity status in determining the presence of breast cancer. The effects of the two sets of factors appear to be additive, so that nulliparous women closely related to a woman with breast cancer have more breast cancer than nulliparous women found in the general population. The underlying factors connected with parity may be the primary exogenous factors, but being inevitably associated with physiological changes found in parous women they have not been identified. Socioeconomic factors are so intimately correlated with size of family, and whether a woman is single or married, that the association between socioeconomic rating and breast cancer may merely reflect the association between parity status and breast cancer.
Women at variable risk for breast cancer may be identified through the age at onset and laterality of breast cancer, and who in the family has the disease. However, additional risk groups may be identified through associated neoplasms, such as the familial occurrence of early and bilateral breast cancer in association with soft-tissue sarcomas, leukemia, and brain tumors, or the familial association of breast and colon cancer, or breast and ovarian cancer. Additional criteria are required for identifying high risk women through some form of biochemical, immunologic, pathologic, endocrine, or genetic marker. No such markers have yet been identified. (Journal received Aug. 1978)
An analysis is undertaken of the frequency of ovulation in 17 groups of women aged 15 to 19 who had been the subjects of other studies. A urine specimen of at least 8 h accumulation had been provided on the 20th or 21st day of a menstrual cycle by 681 women. Analysis is restricted to 431 specimens which had been collected between 11 and 3 days prior to the onset of the subsequent menstrual period. A pregnanediol concentration of less than 1 mg per litre in such a specimen was taken as evidence that the cycle was anovular. The probability of a cycle being anovular was inversely and significantly related to the number of years since menarche, and, with years since menarche held constant, was positively but not significiantly associated with age at menarche. This observation indicates that women with early menarche do not have a longer duration of exposure to anovular cycles than do those whose menarche is delayed, and that variation in the duration of exposure to post-menarcheal anovular cycles does not explain the association of breast cancer risk with early age at menarche. The 17 groups of women were classified into four categories according to ethnic origin and breast cancer incidence in the populations from which they derived. Anovular cycles were not more common in the high-risk groups; indeed, the two centers in the lowest risk category had the highest proportion of anovular cycles.
The possible association between oral contraceptive (OC) use and the risk of breast cancer developing before the age of 45 was investigated by means of a population based case-control study in Sweden and Norway. Information was obtained by personal interview from 422 (89.2%) of all eligible patients with a newly diagnosed breast cancer from May, 1984, to May, 1985, and from 722 (80.6%) of all contacted age-matched controls. A multivariate analysis, which accounted for several possible confounding factors, revealed a significant (p = 0.03) association between total duration of OC use and breast cancer risk. The relative risk (RR) of breast cancer after 12 or more years of OC use was 2.2 (1.2-4.0). OC use for more than 7 years before first full-term pregnancy entailed an increased breast cancer risk (RR = 2.0 [1.0-4.2]) which was of borderline significance. When total duration of use was considered, the risk of breast cancer was virtually unrelated to age at first OC use and latency from first use. The results suggest that long-term use of OCs may increase the risk of breast cancer in young women.
A few risk factors, including increasing age, a history of bilateral premenopausal breast cancer in a first degree relative, a history of breast cancer in the contralateral breast, and residence from an early age in North America compared to Asia, are associated with large relative risks. Other risk factors, including whether or not an oophorectomy has been performed, age at first birth, a history of fibrocystic breast disease, previous exposure to high levels of radiation in the chest, such as sometimes occurred in the treatment of postpartum mastitis or tuberculosis, a history of breast cancer in any first degree relative, socioeconomic status, obesity, and a previous cancer in the ovary or endometrium, are associated with relative risks of at least two- but less than fourfold. Finally, age at menarche, age at menopause, marital status, place of residence, and the white compared to the black race are associated with small but real differentials in risk.
In the present study the assay results of prolactin concentrations in serial samples of blood obtained from premenopausal women with benign or malignant disease of the breast are compared with--and discussed in relation to--findings reported in earlier studies based on single samples of blood taken at various times from a large and ostensibly normal population of women. The finding of an abnormality in nycthemeral prolactin levels in the established disease is considered to strengthen the concept that the same abnormality found in high-risk groups is of aetiological importance.