Women's weight and body composition is significantly influenced by the female sex-steroid hormones. Levels of these hormones fluctuate in a defined manner throughout the menstrual cycle and interact to modulate energy homeostasis. This paper reviews the scientific literature on the relationship between hormonal changes across the menstrual cycle and components of energy balance, with the aim of clarifying whether this influences weight loss in women. In the luteal phase of the menstrual cycle it appears that women's energy intake and energy expenditure are increased and they experience more frequent cravings for foods, particularly those high in carbohydrate and fat, than during the follicular phase. This suggests that the potential of the underlying physiology related to each phase of the menstrual cycle may be worth considering as an element in strategies to optimize weight loss. Studies are needed to assess the weight loss outcome of tailoring dietary recommendations and the degree of energy restriction to each menstrual phase throughout a weight management program, taking these preliminary findings into account.
Around the world obesity is becoming an increasing problem and it is accompanied by major health consequences for the individual and society. This has prompted more people to attempt to prevent weight gain, or to lose weight, by altering dietary habits, eating behavior and physical activity. The National Health Interview Survey conducted in 1998, which included 32 440 Americans, showed that 24% of the male and 38% of the female population were trying to lose weight.1 The percentage of the population attempting to lose weight rose as body mass index (BMI) increased. In men the number trying to lose weight climbed from 6% in the normal weight population (BMI<25) to 50% in the obese population (BMI30). For women the comparable estimates were 24 and 58%, respectively. In a Danish study interviews with 1200 men and women revealed that approximately half of this population had attempted to lose weight.2 Also here the prevalence of trying to lose weight increased with BMI.
Weight loss strategies include eating fewer calories, eating less fat or carbohydrate, exercising more, skipping meals, attending weight loss programs, taking diet pills or diuretics and even fasting for more than 24 h.1 Americans spend more than $33 billion on weight loss products and services every year.1 However, despite the numerous strategies used, the prevalence of obesity is still increasing. More than 30% of Americans are now obese,3 and increasing prevalences are reported from most other parts of the world.4, 5, 6, 7 For those who achieve weight loss, scientific evidence indicates that only 23% of the initial weight loss is sustained 5 years after completing a structured weight loss program.8
When commencing with a diet, cosmetic factors are clearly important motivational factors especially for women, who appear more motivated to diet because of dissatisfaction with their body appearance than men.1 Nevertheless, women may have more difficulty in losing weight, and generally lose less weight than men during weight management programs.9, 10 This may partly be due to gender differences in energy metabolism and in appetite control brought about by secretion of reproductive hormones. In women these hormones control the menstrual cycle and coordinate changes in energy intake (EI), expenditure and storage, while preparing the body for pregnancy every month.11 As reproduction is a primary biological function, these hormones may be such strong mediators of eating behavior that they influence the outcome of a weight loss attempt. The menstrual cycle should therefore be taken into consideration as a factor in the physiology of energy balance in premenopausal women. This paper reviews the literature on appetite, cravings, pattern of food intake, energy metabolism and mood across the menstrual cycle. An in-depth understanding of any mechanisms that change determinants of energy balance during the course of the menstrual cycle could provide helpful tools for the prevention and treatment of obesity. The potential of the physiology related to each phase of the menstrual cycle to optimize weight loss outcome is discussed.
Hormonal changes during the menstrual cycle
The menstrual cycle is coordinated by the hypothalamic – pituitary – gonadal (HPG) axis and is influenced by physiological and pathological changes that occur throughout life.12 The menarche (the first menstruation) is often considered the central event of female puberty, as it signals the commencement of fertility. The average age for menarche is between 12 and 13.5 years.13 It seems to occur most frequently when a young woman reaches around 17% body fat.14 However, it may not be the amount of body fat per se that affects the timing of menarche. Height, weight and skinfold thickness all appear to play a role.15 Race and socioeconomic status have also been suggested to influence menarcheal age.15, 16 The menstrual cycle continues until the onset of menopause around the age of 5017 when the ovaries stop producing estrogens. The reproductive system then gradually shuts down.18
In the majority of women the menstrual cycle averages 28 days, where the day of onset of menstruation is generally referred to as day 1.19 The cycle can be divided into four phases: menstruation or early follicular phase (days 1–4), late follicular phase (days 5–11), periovulation (days 12–15) and the luteal phase (days 16–28).19 The culmination of the follicular phase occurs when ovulation takes place around day 14 or 15. After ovulation the luteal phase begins and lasts about 14 days until the onset of the next menstruation.20 However, when studying energy balance across the menstrual cycle it is often divided into two phases separated by menstruation, with a pre- and postmenstrual phase,19 which is also the case for several of the studies included in this review.
The predominant hormones that regulate the menstrual cycle are gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone and estrogen.20 There are three major forms of estrogen: estradiol, estrone and estriol. Estradiol is the most potent of these.21
Hormones are secreted at various sites. GnRH is secreted by the hypothalamus, the gonadotropins FSH and LH are secreted by the anterior pituitary gland and estrogens and progesterone are secreted from the ovaries. GnRH stimulates the release of LH and FSH from the anterior pituitary, which in turn stimulate release of estrogens and progesterone from the ovaries.22
In the early follicular phase follicular enlargement begins and is characterized by high circulating levels of FSH, which stimulate follicular growth. Levels of plasma LH, estradiol and progesterone are low in this phase. Plasma FSH induces a rise in the concentration of estradiol, which starts in the mid follicular phase and continues until the late follicular phase, when it finally peaks. This event triggers the mid cycle LH surge, which lasts for 40–48 h and induces ovulation. Consequently, the level of plasma estradiol decreases, though it remains slightly elevated throughout the luteal phase.20
When ovulation has occurred progesterone is secreted and its concentration increases until it reaches its peak in the mid luteal phase, and LH and FSH return to their previous levels. If the ovum is not fertilized the plasma concentrations of estradiol and progesterone drop at the end of the luteal phase, which initiates menstruation and thereby a new menstrual cycle.23 The cyclic changes in hormones and body temperature are illustrated in Figure 1.
It has been observed in animal studies that EI is reduced at the time of ovulation, when plasma estrogen levels peak, and that EI is increased after ovulation, when plasma progesterone is elevated.24, 25, 26, 27, 28, 29, 30 Consequently, it has been hypothesized that estrogens reduce appetite and EI and are thus reciprocal to a possible appetite-stimulating effect of progesterone in animals. In humans, a review has summarized EI in relation to menstrual cycle phases in 30 studies, which included a total of 37 groups of women.31 Twenty-seven of the groups demonstrated significantly higher EI in the luteal phase than in the follicular phase. In seven groups no effect was seen, although a general tendency toward a higher luteal EI was observed. The remaining four groups had a higher EI in the follicular phase than in the luteal phase, but these results were nonsignificant.
More recent studies support the findings of luteal hyperphagia,32, 33, 34, 35 where women's EI has been reported to increase with as much as 90–500 kcal/day compared to the follicular phase.33, 34, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46 Thus, most of the data from human studies also indicate that EI changes in response to changes in levels of ovarian hormones, and possibly to estrogens in particular.37, 41, 45, 47 This is supported by data on progesterone-treated ovariectomized rats, where progesterone had no apparent effect on EI.26 This suggests that the observations listed above may be due to an inverse, noncausal association between the plasma concentration of estrogens and EI, rather than due to an appetite-stimulating effect of progesterone.24, 30, 48 In this context estradiol is thought to be the crucial inhibitory signal linking the HPG axis to the neural control of feeding, and thereby inhibiting EI by reducing the amount of food consumed at a single meal.49 Ovariectomy on rats, which disrupts the normal HPG function by preventing the secretion of estrogens and nearly eliminating all estradiol from the circulation, has been shown to increase EI, resulting in a 10–30% increase in body fat.50, 51 This effect of estrogen in animals may also occur in humans. However, it is possible that progesterone, perhaps without an apparent appetite-stimulating effect on its own, may still increase EI when interacting with estrogen. Table 1 presents reference values for normal ranges of estrogen and progesterone in premenopausal and postmenopausal women and in men. It can be seen from Table 1 and Figure 1 that the ranges of estrogen (estradiol) in the luteal phase, where women's EI is increased, are somewhat higher compared to levels in the early follicular phase, in which EI appears to be lower. This suggests that it is perhaps not estrogen per se that mediates EI but that it might also be affected by progesterone. A certain increase in progesterone, as occurs in the luteal phase, may somehow interact with estrogen and thus antagonize the metabolic effects of estrogen and thus increase EI. Further studies are required to examine this hypothesis. Additionally, it would be interesting to investigate whether postmenopausal women, and men (who have lower circulating levels of both estrogen and progesterone than premenopausal women), exhibit similar patterns in EI in response to fluctuations in these hormones.
Estrogens seem to possess potential for a beneficial effect in women attempting to lose weight. However, it has been speculated that women with a greater tendency toward obesity are more sensitive to luteal hyperphagia and perhaps do not respond adequately to this imbalance by lowering EI in the follicular phase when estrogen levels are elevated.19 Additionally, when progesterone is elevated in the luteal phase it has been shown to promote fat storage by decreasing lipoprotein lipase activity in the adipose tissue.51 This results in a decline in plasma triacylglycerols, and potentially in a concomitant increased desire for fat-rich foods.52 This is inappropriate when trying to lose weight as high-fat foods are associated with higher overall EI53 and may also impede weight loss.
The changes in appetite regulation that occur during the menstrual cycle have been suggested to be related to glucose homeostasis, which may be an important determinant of eating behavior in premenopausal women. So far studies in this area have yielded conflicting results. However, it has been proposed that insulin responsiveness is modified by sex hormones54, 55 and that insulin sensitivity is lower in the luteal phase than in the follicular phase.56, 57, 58
It is well known that sex hormones also influence appetite peptides such as ghrelin, leptin, glucagon-like-peptide 1, cholecystokinin and peptide YY.59 Studies of leptin show gender difference with respect to levels of this peptide, also after controlling for body fat.60, 61 However, within-gender difference is also seen as premenopausal women exhibit higher levels than postmenopausal women.61 This suggests that cyclic changes in estrogen-responsive peptides such as leptin occur. However, we have been unable to find studies that have investigated whether sex hormones also interact with appetite peptides to control changes in appetite over the course of one menstrual cycle.
Macronutrient intake, food cravings and the premenstrual syndrome
Reports on macronutrient intake across the menstrual cycle are inconsistent.31 Different studies have shown increases during the luteal phase in carbohydrate,32, 33, 38, 42, 44, 62, 63, 64, 65, 66 fat33, 44, 45, 62, 65 and protein consumption.44, 62 Although reported independently of each other these increases may partly reflect a general increase in appetite rather than an increase in the intake of a particular macronutrient.31 Furthermore, methodological issues such as the ability of the test population to adequately differentiate between carbohydrates and fat can be problematic as there are many ‘sweet-fat’-combination foods (for example, donuts). This challenges the interpretation of data as it is impossible to determine whether the consumption of something like a donut is elicited by a craving for carbohydrate or fat, or perhaps even the combination of the two.
Nevertheless, the increase in carbohydrate consumption has been referred to as carbohydrate craving (craving is defined as an intense desire for a particular food or type of food67). Retrospective data on food cravings provided by 758 women and 380 men showed that women especially craved chocolate, and that they did so more frequently than men, and that they also preferred it to any other type of food.68 Other surveys also indicate chocolate as the most frequently craved food among women,68, 69, 70 and there seems to be no substitute that satisfies a chocolate craving.68 Interestingly, in one of the surveys 85% of women reported that they satisfied their cravings on more than 50% of occasions.68 Moreover, chocolate cravings seem to be more frequent in the luteal phase than at any other time of the cycle.71, 72 This could result in an excessive intake of calories during this phase and consequently affect weight.
Food cravings have been suggested to be influenced by the premenstrual syndrome (PMS).73 This can interfere with normal activities and/or interpersonal relationships, thus distinguishing this syndrome from the premenstrual discomfort experienced by most women. The prevalence of PMS is uncertain as various criteria are used to define the condition. Prevalences from 5 to 60% have been reported, with the highest rates seen in adolescent girls.74, 75 In a study of 313 women screened for PMS by questionnaires, women with PMS exhibited a greater number of ‘episodes of eating’ premenstrually than a control group.32 Furthermore, women with PMS experienced more severe cravings than women who reported no PMS symptoms.66, 73 The etiology of PMS is unknown, but it is interesting to note that food can affect mood, and it is well documented that mood changes are seen premenstrually.31, 66, 73 In a study of 919 women, selected on the basis of their clear patterns of depression during three menstrual cycles, it was observed that depression was positively related to food craving.31
It is possible that PMS and food craving share a common biochemical basis, in which giving into cravings actually works to improve women's mood. However, this has not yet been established.
Although the food consumed during the periods of cravings seems to be high in carbohydrates, it also tends to be high in fat (for example, chocolate).33, 40, 44, 45, 62 As fat provides flavor to foods, it is possible that the sensory properties of a fat-rich food are also an element of the experienced craving.
One study attempted to differentiate between the biological and sensory properties of the satiation of nondrug cravings using chocolate.70 It seems that the urge to smoke a cigarette is satisfied by the pharmacological effect of nicotine,76 whereas chocolate cravings do not seem to be satisfied by the pharmacological properties of chocolate, but more by sensory experiences involving aroma, sweetness and texture.70 In this context a woman's ability to correctly perceive sweet taste seems to play a primary role in determining her hedonic and other perceptual responses to substances such as chocolate.77 This perception of sweetness may vary across the menstrual cycle as sensory research suggests that women's preferences for the sweet tastes and smells are increased in the luteal phase.46, 63 This may be the reason for the higher frequency of craving premenstrually.
Thus the reported changes in macronutrient intake during the luteal phase may be elicited by a natural preference for pleasant tasting, sweet, high-fat foods,19, 78 which may be enhanced premenstrually, thus possibly impeding adherence to a weight management program.
Resting metabolic rate and 24-h energy expenditure
A number of studies have indicated that daily energy expenditure (EE) changes with phases of the menstrual cycle. Premenstrual increases in sleeping metabolic rate (SMR),79, 80 basal metabolic rate (BMR)81, 82, 83, 84, 85, 86 and 24-h EE79, 87, 88 have been reported. However, the increments in EE in the luteal phase vary from one study to another. The mean difference in SMR between the follicular and luteal phase has been reported to be 6.1–7.7%,54, 80 while mean increases in 24-h EE of 2.5–11.5% have been shown.54, 88 The luteal increase in 24-h EE corresponds to an increase of 89–279 kcal.
Nevertheless, EE tends to vary substantially and mean interindividual variation (CV) in BMR has been estimated to 8–11.8%.89, 90 More interestingly, the daily intraindividual variation is wide ranging (1.7–10.4%, mean: 4.6%).89, 91
Some of the factors known to contribute to intraindividual variation in EE are stress, changes in nutritional status, weight, physical activity and seasonal changes.92 Factors that influence interindividual variation include body size, age, gender, nutritional status and activities such as work, leisure pursuits, fidgeting and exercising.92 Interindividual variation in 24-h EE, adjusted for gender, is dependent on family traits, because fat-free mass and fat mass are correlated within families.93 Furthermore, it seems that both 24-h EE and SMR, independent of body composition and spontaneous physical activity, are determined by plasma concentrations of the thyroid hormone triiodothyronine (T3) and norepinephrine.93 Thus, many factors seem to contribute to variations in EE. However, when investigating a woman's EE across one menstrual cycle per se, some of the above-mentioned factors such as size, gender, age and family traits remain constant and thus do not contribute to intraindividual variation. Instead, factors such as T3 and β-adrenergic hormones could more likely explain cyclic variations in EE if, for example, diet and physical activity were to be held constant. One study showed that the β-adrenergic support of resting energy expenditure (REE) tended to be lower when suppressing sex hormones by GnRH antagonist therapy suggesting sympathetic nervous system support of REE as a potential mechanism mediating the reduction in REE with sex hormones suppression.94 However, to this date this possible association has not been clarified.
Nevertheless, it has been proposed that the reported premenstrual increase in EE may be a result, at least in part, of an increase in the concentration of progesterone.81, 87, 88 In studies where increases in EE have been registered, a concomitant increase in progesterone or its metabolic product in urine, pregnandiol (indicating an elevated level of secreted progesterone), has been measured.87, 88 Additionally, progesterone has been shown to be hyperthermic both in normal and in ovariectomized women,95, 96 possibly mediated by a direct influence on the thermoregulatory center in the hypothalamus.97 This suggests that progesterone is a general metabolic stimulator.
It has been suggested that changes in BMR may parallel changes in EI across the menstrual cycle as the two parameters have shown similar patterns independently of each other.88 To investigate this, data on EI and EE need to be obtained from the same group of women. To the authors' knowledge only one study has provided such data. This study showed no correlation between EI and EE, although the changes in the two parameters across the menstrual cycle were of the same magnitude.35 It therefore remains unknown whether the changes in EI across the menstrual cycle are driving changes in EE or vice versa.
The difference in methodologies used in the various trials assessing these parameters probably contributes to the divergence in results in this area. One factor that may be a major bias is time and confirmation of ovulation as the event separating the follicular and luteal phases. In the latter study ovulation was tested repeatedly over numerous cycles in 20 women. Only a few subjects had typical 28-day cycles in which ovulation occurred close to day 14. Ovulation ranged otherwise from day 10 to day 20. Relying on an average 28-day cycle may thus increase error variance.
Hormonal contraceptives and energy balance
In the United States approximately 25% of all women using contraception rely upon oral contraceptives for birth control.98 Several types of oral contraceptives exist. These contain either a combination of synthetically derived components of both estrogen (ethinylestradiol) and progesterone (progestins), or progestins alone. The contraceptive efficacy of these hormones lies in the suppression of ovulation and thickening of the cervical mucus,99 which prevents pregnancy by preventing implantation of a fertilized egg. These contraceptives interfere with the naturally occurring fluctuations in hormones in the menstrual cycle and it can therefore be anticipated that this may exert an effect upon energy balance, which may either benefit or impede weight loss as the natural fluctuations in women's sex hormones are controlled.
To date only a few studies have investigated the effect of oral contraceptives on energy and macronutrient intake, and the findings are contradictory. Significant increases in fat and EI have been reported in women using oral contraceptives compared to non-pill users.100, 101 But there are also studies showing no differences in EI between pill users and non-pill users.35, 102, 103 When interpreting the above-mentioned results one should consider the formula of the oral contraceptives that are investigated in these studies. Combined and progestin-only pills as well as triphasic contraceptives are used. It is possible that the different formulas of oral contraceptives may result in diverse effects on EI. Moreover, the methods used for registering EI vary from one study to another. More studies are warranted to clarify this issue.
The effect of oral contraceptives on EE has also been studied. It appears that physiological variations in the secretion of estrogens and progesterone affect EE, so exogenous administration of these hormones is likely to have an effect. One study showed that women who used oral contraceptives had a significantly increased BMR (almost 5%) compared to non-pill users, even after adjustment for differences in body weight and self-reported levels of physical activity.104 However, this was in contrast to a number of other studies, which reported no difference,35, 100 or even a decrease in daily BMR102 and EE88 with the use of oral contraceptives compared to no use. It is therefore not possible to draw any conclusions about the effect of oral contraceptive agents on EE.
Body weight in relation to oral contraceptive use has also been investigated.105, 106, 107 A recent review evaluated the association between contraceptive use and changes in body weight by including randomized controlled trials that compared oral contraceptives with placebo or with another oral contraceptive.106 Weight change comparisons during 3–24 cycles of 47 different contraceptives and/or placebo pairs were represented. Most comparisons showed no substantial difference in body weight, which is supported by other studies.105, 107 However, a minority of studies reported a trend toward weight gain with oral contraceptive use compared to placebo. It was not possible to detect whether this was due to the dosage of estrogens or progestins in the respective contraceptives, or due to other factors independent of the oral contraceptives.
Recently, injections of combined hormonal formulations and progestins-only contraceptives have been introduced. A recent study showed a significantly greater increase in body weight for women who received intramuscular injections of Depo-Provera, a progestins-only contraceptive, for a period of 30 months, compared to women using no hormonal contraception.108 Other studies support this finding.108, 109, 110 This may indicate a potential weight-inducing effect of progestins. However, it is uncertain whether the increase in body weight was caused by the mode of administration (injection vs oral ingestion), which may alter the metabolic effects of this hormone; or whether the hormone itself, regardless of how it is administrated, is weight promoting.
Based on the presented data it seems that oral contraceptive use has no impact on body weight. The observed weight changes in the trials did not exceed those of the natural fluctuations in body weight which can occur during a single day or across a menstrual cycle, for example, where women may experience a minor increase in body weight premenstrually and during the first days of the menstruation due to water retention.111 However, weight gain may be promoted when transdermal contraceptives with specific progestin-only formulations are used.
Generally, our knowledge of the effect of hormonal contraceptives on energy balance is limited. Thus it remains unclear to what extent hormonal contraceptives that interfere with hormones of the normal menstrual cycle may influence weight loss efforts.
Implications for weight management programs
It may be worth considering which stage of the menstrual cycle is appropriate for initiation of a weight loss regimen. It appears that the body's physiological needs for energy are increased premenstrually, which gives rise to cravings and an increased EI. One strategy may be to commence the diet on the first day of menses (day 1), or in the late follicular phase (days 5–11), when food cravings appear to be less intense, thereby making it easier to adapt to energy restriction and establish a good basis for adherence to the diet. Carbohydrate, fat and total EI could be moderately increased 5–8 days before menstruation to meet the body's increased energy demands, rather than rigidly adhering to a suboptimal caloric level. Cravings for carbohydrate should be alleviated mainly by foods such as fruit, which, apart from sugar, contain some vital nutritive elements. As chocolate is frequently craved, and is seemingly irreplaceable, a small daily allowance of chocolate may improve adherence to the diet in the premenstrual period, preventing a sudden overconsumption of craved foods, such as chocolate, due to a longer period of suppressing the craving. Dark chocolate may be preferable as it contains the healthier monounsaturated oleic acid. Furthermore, moderate consumption of dark chocolate may be associated with reduced risk of vascular diseases as its high content of cocoa contains nutrients which have been shown to exert strong antioxidant effects in vitro and in vivo in humans.112, 113 Additionally, it may be of interest to investigate whether the powerful taste of dark chocolate compared to light chocolate may better satisfy a woman's craving and thus preventing overconsumption of chocolate. No data on this subject has yet been published.
It may be relevant to investigate which food items are actually eaten to examine whether it is realistic to expect that craved foods (other than chocolate) can be successfully replaced by foods that contain less sugar and fat, while still satisfying women's cravings. Women who suffer from PMS, and thus from more severe symptoms of depression and food cravings and so on, may benefit from some kind of nutritional supplement/medication, as conscious changes in food intake alone may not be sufficient to relieve the premenstrual discomfort. It is not the purpose of this review to evaluate possible treatments for PMS, but any supplement that can diminish premenstrual depression and thus improve mood would probably improve these women's adherence to a diet.114
Long-term weight management programs
When attempting to develop a systematic weight management program based on menstrual phases, factors that may affect the chances of success must be considered. Pretreatment body weight is an important independent predictor of weight loss and slightly overweight women may not respond as well to a weight management program as women who are obese.115 Nor do all women experience changes in cravings and in food intake related to the menstrual cycle. This review addresses whether hormonal changes affect different components of energy balance, such as food intake, but food intake can also affect hormones. Women who exhibit cognitive restrained eating, for the purpose of either losing weight or controlling other factors, may experience irregularities in the menstrual cycle116 due to insufficient EI.117 They therefore cannot rely on a weight management program based on the assumption of a regular menstrual cycle. In investigations of the effects of the menstrual cycle on energy balance components women have usually been kept on energy balanced diets to prevent weight changes. However, any given cyclic effect found under these circumstances (when energy balance is maintained) may change when women adhere to an energy-deficient diet and consequently lose weight. This may induce an upregulation of appetite-stimulating hormones, for example, ghrelin,118, 119 along with an altered ratio between estrogens and progesterone, which may constitute a mechanism of counterregulation. It may therefore be necessary to take into account the changing metabolic state when dieting continues over a longer period by readjusting diet composition, calorie consumption and physical activity level.
In the luteal phase of the menstrual cycle it appears that women's EI and EE are higher than in the follicular phase. Additionally, women more frequently experience food cravings, particularly for foods high in carbohydrate and fat, in the luteal phase. This indicates that it may be worth taking the underlying physiological mechanisms related to each menstrual phase into account in weight management attempts.
Short-term studies are needed to assess the weight loss outcome, that is, initial weight loss and dropout rate, for weight loss strategies involving changes in diet composition and energy restriction tailored to each menstrual phase based on the presented data. This may provide a useful tool for improving adherence to weight management programs and consequently enhance weight loss outcome.