Key words
hyperandrogenism - diet - anti-inflammatory - testosterone - sex hormone - binding globulin - free androgen index
Introduction
Hyperandrogenism (androgen excess) is a common, heterogeneous, and endocrinal
condition affecting 5–10% of women in their reproductive age [1]
[2]. Hyperandrogenism has several possible causes, including tumors of the
adrenal or ovary, congenital or acquired adrenal hyperplasia, Cushing’s
disease, acromegaly, hyperprolactinemia, and various medications [1]
[2]. However, there are also known clinical cases in which distinguishing
specific causes related to androgen excess can be challenging. In women with
hyperandrogenism, polycystic ovary syndrome (PCOS) is diagnosed in
80–85% of cases [1]
[3], making it the most common cause of
androgen excess.
High heterogeneity in clinical manifestations is observed among women with androgen
excess. For this reason, abnormalities of the hypothalamic-pituitary unit, the
ovary, and the adrenal are usually described as the most probable, and primary
pathogenesis involves the androgen excess [4]
[5]
[6]. Nowadays, it is well known that both
environmental factors and insulin resistance have the most significant role in the
pathogenesis of hyperandrogenism. Hyperinsulinemia induced by insulin resistance
stimulates thecal androgen production and a decrease in hepatic sex hormone-binding
globulin (SHBG). It is the strongest hypothetical pathology of hyperandrogenism,
proved in many previous and recent reports [7]
[8]
[9]
[10]. Women with hyperandrogenism are at higher risk of many health
problems, including hypertension, coronary heart disease, obesity, type 2 diabetes,
gestational diabetes, anovulatory infertility, spontaneous abortion, and endometrial
or breast cancer [10]
[11]
[12]
[13].
Moreover, the clinical phenotype of an individual patient may change over time [1]. Thus, hyperandrogenism diagnosis
depends on clinical manifestation determination and biochemical androgen excess
measurements. Obesity is a critical factor that worsens the clinical consequences of
androgen excess, such as reduced frequency of ovulation, irregular menstrual cycles,
reduced infertility, and polycystic ovaries. Obesity is also strongly related to
high levels of male hormones such as testosterone. An increase in testosterone level
causes hirsutism, defined as excessive male-pattern terminal hair growth [14]
[15]. This unwanted facial or body hair growth is ’the most common
clinical manifestation of hyperandrogenism. Hirsutism is diagnosed in about
80% of women who suffer from androgen excess and is strongly related to
psychological morbidity that negatively influences the quality of life of
hyperandrogenic women [16]. The diagnosis
of hyperandrogenism is based on hirsutism and includes other clinical criteria such
as acne, androgenic alopecia, and virilization. Androgenic alopecia also worsens the
quality of life, influencing psychological well-being and self-esteem [17]. Elevated circulating androgen levels
cause virilization, a relatively uncommon clinical finding of hyperandrogenism [18]. However, virilization is
characterized by many clinical features, such as deepening of the voice, increasing
muscle mass, and decreasing breast size, which also influences psychological
morbidity and can worsen anxiety and depression [18].
The primary management of hyperandrogenism is based on a healthy lifestyle, which
consists of a nutritious diet, regular exercise, and achieving and maintaining a
healthy weight. However, limited reports have explained the influence of diet and
lifestyle modifications on the clinical manifestations of hyperandrogenism. Studies
have mainly focused on managing the most common related causes or clinical symptoms
and have shown the benefits of weight loss in women who are obese or overweight and
with PCOS [19]
[20]
[21]
[22]. According to
International Evidence-Based Guidelines, lifestyle interventions are considered to
be the primary early management strategy for women with hyperandrogenism and PCOS.
Lifestyle interventions are traditionally defined as those designed to improve
dietary intake or physical activity through appropriate behavioral support.
This study aimed to assess the associations between lifestyle habits and dietary
patterns in women with diagnosed hyperandrogenism. Then, the effectiveness of
lifestyle modifications was determined, especially the influence of a reduced
glycemic load diet and anti-inflammatory food intervention on the clinical
manifestations of hyperandrogenism and anthropometry and biochemical results.
Material and Methods
Forty-four women of reproductive age (18–49 years) were enrolled in the study
group. Fourteen women were control subjects. Informed consent to participate in this
study was obtained from patients and healthy controls. All participants had the
right to receive information and ask questions before, during, and even after the
study. Four women resigned after 7 days of dietary intervention and 10 more women
did not start the program when given the dietary advice. However, these 14 women
gave their written consent to stay involved in the study as the control group. The
30 patients and 14 controls were under the care of a consultant gynecologist and
endocrinologist from the Jagiellonian University Hospital in Krakow. The certified
dietitian adapted and managed a dietetic and sports activity intervention. The
inclusion criteria for the study were: age 18–49 years, no use of hormonal
contraception for at least 6 months (all women involved in this study declared no
use of contraception for one year before the study participation), and other health
problems such as excessive body weight (body mass index
[BMI]>25 kg/m2), excessive body hair, acne
especially in the jaw area, irregular or lack of menstrual cycles for the last 6
months, hair loss with characteristic male pattern curves (Ferriman-Gallway score
≥ 8). Free androgen index (FAI) was considered one of the inclusion
criteria. The FAI cut-off value was >5 based on the recommendations for the
Polish population constituted by the Polish Society of Endocrinology, the Polish
Society of Gynecologists and Obstetricians, and the Polish Society of Gynecologic
Endocrinology [23]. Menstrual problems
were assessed according to the observations made and described by women from the
study group. The menstrual problems or the lack of menstruation were assigned when
periods occurred less than 25 days or more than 35 days apart, missing three or more
periods in a row, much heavier or lighter than usual menstrual flow, periods lasting
longer than seven days or were accompanied by pain, cramping, nausea, or vomiting,
or when bleeding or spotting happened between menstrual periods. Exclusion criteria
were age below 18 or more than 49 years, use of hormonal contraception within 6
months of study entry, pregnancy, congenital adrenal hyperplasia, Cushing’s
syndrome, hyperprolactinemia, and lack or withdrawal of consent to participate in
the study.
Dietetic intervention
A low glycemic index diet with anti-inflammatory elements and a slight energy
deficit was applied in this study. Based on the literature, this type of diet
can effectively affect the treatment of hyperandrogenism. The consumption of
foods with a low glycemic index, such as a diet, helps keep blood glucose levels
stable, which reduces insulin secretion. Reducing insulin levels is key to the
treatment of hyperandrogenism, as it helps reduce the production of androgens by
the ovaries, which can ultimately alleviate the symptoms of this condition. In
addition, an anti-inflammatory diet reduces inflammation in the body that may be
associated with hyperandrogenism, which aids in the comprehensive treatment of
this disease [24]
[25]
[26]. The two-month, low glycemic index
diet with anti-inflammatory elements and slight energy deficit was prepared and
advised to all participants. The detailed characterization of diet components
with potential influence is described in [Table 1]. The diets were in the calorie range of 1,600 to
1,900 kcal and were matched to the needs of patients in the study and
control groups. The calories of the diets were adjusted, considering the total
energy requirements and physical activity, general lifestyle, and eating habits.
The product was considered to be of low glycemic index (GI) when its GI was less
than 55 compared to products with an average GI, with values between 56 and 69,
and those with a high GI ≥ 70. The assessment of the GI of the food
products was based on the GI values of more than 2,480 individual food products
(available in the online-only appendix), characterized by Fiona et al. [27]. The diet included a reduced
intake of carbohydrates at approximately 45–50% of the caloric
requirements (200 g of carbohydrates in the 1600 kcal diet,
213 g in the 1700 kcal diet, and 238 g in the 1900 kcal diet).
The intake of saturated fat was reduced to approximately 10%
(53 g of fat in the 1600 kcal diet, 57 g in the 1700 kcal diet,
and 95 g in the 1900 kcal diet). For a higher protein intake, at
approximately 20–30% energy throughout the day, translated to
80 g protein in the 1600 kcal diet, 85 g in the 1700 kcal diet,
and 95 g in the 1900 kcal diet. Dietary fiber intake in all diets (at
1600, 1700, and 1900 calories) was 40 g. The daily menus included four
meals for the 1600 and 1700 kcal diets and five meals for the 1900 kcal diet; in
the first two diets, the percentage distribution of energy was breakfast:
30%, second breakfast: 15%, lunch: 35%, and dinner:
20%. In the highest caloric diet, the energy distribution was breakfast:
25%, second breakfast: 15%, lunch: 30%, afternoon tea:
10% energy, and dinner: 20% of the total energy. Breakfast and
lunch were the most important meals of the day. Thus, they included the
essential portions of food. Women ate cocoa pancakes with blackberries and
almonds, avocado and soft-boiled egg sandwiches, wrapped omelets with kale and
sprouts, oatmeal with berries and chia seeds, buckwheat with green pear, quinoa
with berries, and tuna and vegetable sandwiches. The second breakfast included
light snacks, such as sandwiches with homemade hummus and vegetables, pear and
almond smoothie, country cheese with nuts and fruit, or chia pudding. For lunch,
the participating women ate puff pasta with salmon and mushrooms, casserole with
chicken and cauliflower, cod with vegetables, and buckwheat groats. Salads
included red bean and tuna salad, pasta salad with cranberries and chicken, mini
zucchini pizzas, buckwheat yogurt pancakes, and poultry strips in sesame with
vegetables and yogurt sauce were often eaten for dinner.
Table 1 Characteristics of dietetic
intervention.
|
Nutritional component
|
Nutrients
|
Potential effect
|
|
Carbohydrate products
|
Oatmeal, buckwheat groats, buckwheat flour, pearl groats,
couscous groats, brown rice, quinoa, durum wheat, and pasta
cooked al dente.
|
Avoiding carbohydrates with a high glycemic index can reduce
the risk of endocrine disruption associated with
hyperandrogenism.
|
|
Protein/ plant protein
|
Natural yogurt, cottage cheese, camembert cheese, cream
cheese, cottage cheese, mozzarella cheese, goat cheese, feta
cheese, 2% milk, buttermilk, and kefir, chickpeas,
lentils, beans, and animal protein sources, such as poultry
meat (chicken, turkey), fish (cod, salmon, tuna), eggs, and
shrimp.
|
Including more plant protein can lower androgen levels in
women with PCOS and hyperandrogenism.
|
|
Fat
|
Avocados, pumpkin seeds, flax seeds, sunflower seeds, chia
seeds, walnuts, cashews, hazelnuts, Brazil nuts, almonds,
and vegetable fats such as canola oil, olive oil, and
flaxseed oil
|
The fat intake should be in the proportions between
20% and 35% of total calories. High-fat
diets, especially when coupled with nutrient excess, can
trigger lipid accumulation in both fat and non-fat tissues.
|
|
Omega-3 fatty acids
|
Avocados and fatty fish such as salmon, seeds, and vegetable
oils (canola oil, flaxseed oil, and olive oil).
|
Supplementation with these acids can lower testosterone
levels in overweight and obese women and regulate
menstruation
|
|
Vegetables, fruits, vitamins, minerals and fibers
|
Green and red vegetables such as red bell pepper, tomato,
cherry tomato, broccoli, bean sprouts, lamb's
lettuce, spinach, arugula, and lettuce accounted for the
most significant proportion; berries with high
anti-inflammatory potential, such as strawberries,
raspberries, blueberries, and blackberries.
|
Increasing fiber intake can lower androgen levels and
decrease free testosterone. Magnesium supplementation can
lower testosterone and dehydroepiandrosterone-sulfate levels
in women with hyperandrogenemia. Zinc has anti-androgenic
effects and inhibits androgen production, and its deficiency
can lead to endocrine disruption. Low vitamin D levels can
predispose to insulin resistance and metabolic disorders
|
Data collection
Data for dietary intake, health habits, and medical records were collected
retrospectively (before dietetic intervention) and at the end of the study
(post-dietetic intervention). The questionnaires were prepared based on the Food
Frequency Questionnaires (FFQs), the most common and validated tool used in
dietary surveys. The FFQs are a type of dietary assessment tool that attempts to
capture the usual food consumption of an individual by querying the frequency at
which the respondent consumed food items based on a predefined food list [28]. The FFQ was used in the context
of specific food lists selected for this study. A questionnaire and medical
interview were advised to collect the data mentioned above. Pre- and
post-dietetic intervention data were compared to assess the influence of
recommended diets and applied sports activities on anthropometrics,
biochemistry, and changes in clinical symptoms. Physical and anthropometric
parameters (weight, height, BMI, hirsutism) of all participants were measured.
Body weight was taken using a high-precision digital scale, Charder MA601
(Charder Electronic, Taiwan). Height was determined using a high-precision
digital stadiometer (Seca 242, Hamburg, Germany). BMI was calculated from the
measured body weight and height by dividing weight [kg] by height
[m2] and calculated as kg/m2. The individuals with
a BMI >25 kg/m2 were considered overweight,
those with obesity had a BMI > 30 kg/m2,
while normal individuals had a BMI in the range of 18.5 to
24.9 kg/m2
[29]. The measurements were taken in accordance with the criteria of
the World Health Organization [30]. A
physician specializing in gynecology and endocrinology graded hirsutism using
the common modified Ferriman-Gallwey score (mFG) [31]. According to the mFG scale,
hirsutism was diagnosed for scores > 5. To assess hirsutism, terminal
hairs were scored in nine body areas, namely the upper lip, chin, chest, upper
abdomen, lower abdomen, upper back, lower back, thighs, and upper arms. The
clinical symptoms of hyperandrogenism were recorded at the beginning of the
study and the end of the follow-up period. Blood samples were collected from all
study participants after they fasted overnight between 7 and 9 AM during the
first 5 days of the spontaneous menstrual cycles. Serum was collected and
assayed to determine total testosterone, prolactin, cortisol, 17
hydroxy-progesterone, and serum hormone-binding globulin (SHBG) levels. The
total testosterone, prolactin, cortisol, and 17 hydroxy-progesterone were
measured based on electrochemiluminescence (ECL) technology on a biochemical
autoanalyzer Cobas e 422 (Roche Diagnostics GmbH, Mannheim, Germany). SHBG was
measured based on electrochemiluminescence in Elecsys 2010 (Roche Diagnostics
GmbH, Mannheim, Germany). The free androgen index (FAI) was calculated based on
total testosterone and SHGB concentration using the following formula: FAI
= total testosterone [nmol/L]/SHBG
[nmol/L]*100. The intra-assay and interassay coefficients of
variation of the aforementioned assays were all <10%.
Statistical analysis
The SPSS software (version 16) was used to perform statistical analysis. The
t-test method was applied for quantitative variables, presented as the mean
(± standard deviation; SD). The qualitative variables were presented as
the number (%) between the two groups. The chi-square method was used
for the qualitative variables. The multivariate logistic regression model was
used to examine the significant variables. The independent variables were
determined using the backward method after adjusting for confounders. For
classifying food products, the factor analysis model of main dietary components
was used to determine the most significant food-related factors. The most
significant food-related factors were entered into the univariate logistic
regression model separately. Finally, the univariate analysis models were
applied to the multivariate logistic regression model using the forward method
to identify the independent risk factors. P<0.05 was considered
statistically significant.
Results
Most women who participated in the study were aged between 18 and 23 years, whereas
the minority was between 41 and 49 years old. The mean age of the participants was
31 years. The examined characteristics of the study participants are summarized in
[Table 2] and [3], respectively, for patients and
healthy controls. The general satisfaction was assessed by asking the study group to
rate their overall health-related well-being on a scale from 1 to 5, with 1
indicating poor well-being and 5 indicating excellent well-being ([Fig. 1].) The overall satisfaction
presented as an increase in the mean value from 2.23 to 3.52 throughout the study
(p<0.001). Pre- and post-dietetic intervention differences in food
preferences are shown in [Table 4]. The
observed changes were consistent with the applied dietary intervention and
indirectly indicated a good level of compliance with the changes in the diet. As a
result, a decrease in total testosterone levels and an increase in levels of SHBG,
respectively, were observed ([Fig. 2]
and [3]). The differences between total
testosterone and SHBG, measured before and after dietetic intervention, were
statistically significant ([Fig. 2] and
[3]). Those changes correlated with
the introduction of a low glycemic index diet (p<0.003 and p<0.001,
respectively). The mean FAI values calculated before and after dietetic intervention
in all hyperandrogenic women were 292% and 172%, respectively. The
difference between FAI results before and after the dietetic intervention was
statistically significant, and the p-value was 0.001. Additionally, the correlations
between nutritional components, supplements, hyperandrogenic clinical symptoms, and
testosterone, SHBG before and after the dietetic intervention were statistically
analyzed. None of the consumed dietary supplements were associated with a decrease
in total testosterone, with omega 6 acids supplementation correlating with higher
concentrations of SHBG (p<0.001). A decrease in total testosterone
positively correlated with decreased symptoms of hirsutism (p<0.041) and
acne (p<0.012). An increase in SHBG concentration correlated negatively with
the prevalence of abnormal menstruation (p<0.010) and infertility
(p<0.012). [Table 5] shows
factors correlating significantly with decreased total testosterone levels and
increased concentration of SHBG. These factors include probable causes (for example,
dietary changes) and probable effects (for example, lower prevalence of
hyperandrogenism symptoms) of observed results. Particularly, the selected factors
differed among measured hormonal indicators.
Fig. 1 The level of reported general satisfaction was collected before
and after the dietetic intervention. Data were collected using
questionnaires based on a 1 to 5 points scale, where 1 means the lowest and
5 was the highest level of life satisfaction. The p-value was
p<0,001.
Fig. 2 Total testosterone levels before (blue box) and after (green
box) the dietetic intervention. Data are presented as ng/dl. The
p-value<0.003.
Fig. 3 SHBG levels before (blue box) and after (green box) the
intervention. Data are presented as nmol/l. The p-value<0.001.
Table 2 Characteristics of patients and the differences
between anthropometric, hormonal, and clinical variables pre- and
post-intervention.
|
Variables
|
Pre-intervention
|
Post-intervention
|
P-value
|
|
(N=30)
|
(N=30)
|
|
|
Mean
|
Mean
|
|
|
Weight (kg)
|
82.65
|
79.03
|
0.350
|
|
BMI
|
29.61
|
27.85
|
0.070
|
|
Physical activity level
|
3.70
|
3.17
|
0.120
|
|
Overall well-being
|
2.23
|
3.52
|
0.001
|
|
Total testosterone (ng/dL)
|
75.73
|
64.67
|
0.001
|
|
SHBG (nmol/L)
|
26.78
|
40.92
|
0.001
|
|
FAI
|
10.21
|
5.97
|
0.001
|
|
Abnormal menstruations
|
0.70
|
0.37
|
0.009
|
|
Acne
|
0.58
|
0.34
|
0.050
|
|
The lack of symptoms
|
0.47
|
0.10
|
0.001
|
|
Hair loss
|
0.35
|
0.17
|
0.100
|
|
Hirsutism
|
0.50
|
0.41
|
0.500
|
|
Sleep disturbance
|
2.97
|
2.62
|
0.100
|
|
Stress
|
2.41
|
3.10
|
0.001
|
BMI: body mass index; FAI: free androgen index; SHBG: sex hormone-binding
globulin.
Table 3 The basic characteristics of the control
group.
|
Variables
|
Pre-intervention
|
Post-intervention
|
P-value
|
|
(N=14)
|
(N=14)
|
|
|
Mean
|
Mean
|
|
|
Weight (kg)
|
82.65
|
83.03
|
0.520
|
|
BMI
|
29.61
|
29.69
|
0.710
|
|
Physical activity level
|
3.70
|
3.62
|
0.120
|
|
Overall well-being
|
2.23
|
2.25
|
0.100
|
|
Total testosterone (ng/dL)
|
75.73
|
76.1
|
0.100
|
|
SHBG (nmol/L)
|
26.78
|
27.01
|
0.100
|
|
Abnormal menstruations
|
0.70
|
0.67
|
0.100
|
|
Acne
|
0.58
|
0.54
|
0.100
|
|
The lack of symptoms
|
0.47
|
0.48
|
0.100
|
|
Hair loss
|
0.35
|
0.37
|
0.100
|
|
Hirsutism
|
0.50
|
0.51
|
0.100
|
|
Sleep disturbance
|
2.97
|
2.92
|
0.100
|
|
Stress
|
2.41
|
2.51
|
0.100
|
|
Overall well-being
|
2.23
|
2.25
|
0.100
|
BMI: body mass index; FAI: free androgen index; SHBG: sex hormone-binding
globulin.
Table 4 Pre- and post-dietetic intervention differences in
dietary patterns. A lower value pre-intervention versus
post-intervention means a greater tendency to consume a given
product.
|
Product
|
Pre-intervention
|
Post-intervention
|
P-value
|
|
(N=30)
|
(N=30)
|
|
|
Mean
|
Mean
|
|
|
Pasta
|
2.94
|
1.89
|
0.001
|
|
Bread
|
2.11
|
1.31
|
0.001
|
|
Cereals
|
2.32
|
1.41
|
0.001
|
|
Supplements
|
3.23
|
2.38
|
0.005
|
|
Meat
|
2.00
|
2.55
|
0.059
|
|
Fish
|
3.58
|
3.17
|
0.053
|
|
Sweets
|
4.58
|
5.24
|
0.006
|
|
Legumes
|
4.03
|
2.55
|
0.001
|
|
Diary
|
1.85
|
2.07
|
0.249
|
|
Fatty products
|
2.70
|
2.34
|
0.170
|
|
Vegetables
|
2.00
|
1.17
|
0.001
|
|
Salad
|
2.91
|
2.38
|
0.014
|
|
Fruits
|
1.97
|
2.00
|
0.870
|
|
Nuts
|
3.62
|
2.03
|
0.001
|
|
Confection
|
2.76
|
3.10
|
0.048
|
|
Fast food
|
2.79
|
3.45
|
0.003
|
|
Chips
|
2.73
|
3.76
|
0.001
|
|
Sugar
|
2.17
|
3.89
|
0.001
|
|
Alcohol
|
2.88
|
3.27
|
0.012
|
|
Soft drinks
|
4.20
|
4.34
|
0.598
|
|
Coffee (black)
|
0.23
|
0.03
|
0.017
|
|
Milk
|
0.14
|
0.58
|
0.001
|
Table 5 A list of factors of significant correlation with
observed changes in total testosterone and SHBG plasma
levels.
|
Total Testosterone
|
SHBG
|
|
Factor
|
P-value
|
Factor
|
P-value
|
|
Sleep disturbances
|
0.006
|
Sleep disturbances
|
0.002
|
|
Stress
|
0.013
|
Stress
|
0.001
|
|
Abnormal menstruation
|
0.025
|
Smoking
|
0.023
|
|
Increased androgens level
|
0.014
|
Increased androgens level
|
0.001
|
|
Physical activity
|
0.006
|
Abnormal menstruation
|
0.047
|
|
Overall well-being
|
0.003
|
Overall well-being
|
0.001
|
|
Fish consumption
|
0.001
|
Bread consumption
|
0.001
|
|
Vegetable consumption
|
0.003
|
Meat
|
0.001
|
|
Salad consumption
|
0.009
|
Fish
|
0.001
|
|
Nuts consumption
|
0.019
|
Salad consumption
|
0.049
|
|
Confection consumption
|
0.003
|
Fruits consumption
|
0.023
|
|
Sugar consumption
|
0.001
|
Alcohol consumption
|
0.004
|
|
|
Soft drinks consumption
|
0.001
|
SHBG: sex hormone-binding globulin.
Discussion
This study demonstrates a significant association between food-preferred status and
dietary patterns with hyperandrogenism phenotype involving testosterone and SHBG
levels. The results also showed an improvement in women’s well-being status
after dietary intervention. A significant finding was the positive correlation
between Western dietary patterns and the lack of physical activity with the
progression of clinical hyperandrogenism in women before dietary intervention.
Before starting the study, the food products used in the daily diet and individual
meals differed significantly from the standards advised in the nutritional treatment
of hyperandrogenism. After the dietary intervention, most women lost weight by
following a reduced diet with a low glycemic index of anti-inflammatory nature.
Similar observations were drawn in a study conducted by other researchers who showed
that a low-calorie diet with a low glycemic index significantly affected weight loss
and insulin resistance, and clinical and biochemical features of hyperandrogenism
significantly improved after 6 months of using the diet [32]. In the current study, even a
two-month dietary intervention and physical activity were enough to initiate
positive effects in some of the clinical manifestations of hyperandrogenism and a
decrease in testosterone and SHBG levels. Our study described similar, favorable
effects over 2 months. Obtained results suggested that the long-term use of a low-IG
diet could significantly reduce the symptoms of clinical hyperandrogenism and the
problems related to menstruation and fertility. It is possible that hormonal
regulation was achieved with the negative energy balance and the individual
nutrients found in the advised diet. The introduction of omega-3 fatty acids
decreased animal protein consumption in favor of plant-sourced protein, little
sugar, and sweeteners. Including antioxidants and moderate physical activity may
improve the overall health of women with PCOS and other endocrinopathies [33]. Our results are very similar to those
of earlier published studies. Kazemi et al. [34] investigated the effect of the DASH diet (Dietary Approaches to Stop
Hypertension, anti-inflammatory diet with low GI) on female hormonal parameters and
the relationship with obesity. They showed that this way of nutrition translated
into a decrease in insulin resistance, a decrease in hyperandrogenism symptoms and
obesity phenotype, and an improvement in ovarian morphology [34]. Hormonal changes induced by dietary
changes can be observed shortly after intervention onset. In one of the studies
conducted among patients with endocrinopathy, there was a decrease in free
testosterone in 5 out of 6 women by an average of 62% after 90 min
after eating a meal rich in complex carbohydrates and high in fiber [35]. Berrino et al. [36] investigated the relationship between
the Mediterranean diet and hormonal changes. They observed a decrease in SHBG by an
average of 25.2% and a decrease in testosterone levels by an average of
19.5% by switching from a typical Italian diet to a diet with a reduced
glycemic index, a negative energy balance, and including anti-inflammatory elements.
The women who followed this diet for 18 weeks noticed reduced body weight and
improved lipid and hormonal parameters [36]. Women with hormonal problems often believe that accompanying
diseases prevent them from achieving and maintaining proper body weight. Researchers
studying the effect of diet on body weight in women with PCOS, particularly the
hyperandrogenic type, often notice a relationship between the occurrence of the
disease and the belief that it is difficult to lose body fat despite many attempts.
Our study shows that introducing advised eating habits reduces body weight by an
average of 1.3 kg per month. Physiologically, it is not clear why women with
hyperandrogenism exhibit increased body weight. Women with hormonal problems may be
predisposed to accumulate body fat, but this effect is usually caused by unhealthy
eating habits and decreased physical activity. Before the dietetic intervention,
most women in our study group were overweight or obese. Excessive body weight
significantly affects SHBG and total testosterone [37]. The very change in eating habits
often results in weight reduction, thus improving insulin sensitivity, removing
excess testosterone, and alleviating symptoms caused by an increase in the level of
this hormone. Our observations are consistent with those reported by Campbell et al.
[38], who investigated the effects of
a reduced diet on sex hormone levels. They observed that in women who reduced their
body weight by at least 5%, testosterone levels decreased and SHBG levels
increased, followed by a decrease in hirsutism symptoms [38]. Hyperandrogenism, insulin resistance,
and obesity are closely related and contribute to lowering SHBG and increasing free
testosterone levels. These relationships are expected because SHBG binds to
testosterone with high affinity, thus reducing free testosterone concentration [37]. Another dietary intervention carried
out in a study on women of childbearing age aligns with our results and showed that
using a reduced-calorie diet with a low GI and an anti-inflammatory diet helps in
weight loss and contributes to better glucose tolerance and lower testosterone
levels [39]. Our study showed an
improvement in reproductive parameters and regulation of menstruation in many women
using a low GI diet and an anti-inflammatory diet compared to the standard diet
consumed before the study. Before the study, only 23.5% of women had normal,
regular cycles, while after finishing the diet, 42.9% of women reported an
improvement in the regularity of menstrual cycles [40]. Other researchers, such as
Onieva-Zafra et al. [41], observed that
after 12 weeks of dietary intervention, 63% of the examined women began to
have regular periods. They noted a correlation between the consumption of fish and
nuts containing anti-inflammatory omega-3 fatty acids and their effects on the
regulation of menstruation [41]. Stress
plays a vital role by disrupting the proper secretion of testosterone and SHBG. The
vast majority of women before the study were exposed to chronic stress. At the end
of the study, the participants reported a reduction in stress factors, which
correlated with decreased testosterone and higher SHBG levels. These results align
with those of another study, which included 206 women with PCOS and hirsutism, and
observed a significant impact of lifestyle changes, including a reduction in stress
factors that translated into an increase in SHBG and a decrease in total
testosterone levels [42]. Shafrir et al.
[43] assessed the effects of stress
and alcohol consumption on androgens and SHBG. In their study, women with
hyperandrogenism resigned from shift work for full-time work, eliminated the most
stressful factors from their lives, and reduced their alcohol consumption to two
glasses of wine per month. These three changes improved the laboratory measurements
of the above-mentioned parameters. The main limitation of our study was the
relatively shorter duration of 2 months, which may be the possible cause of the lack
of change in the incidence of hyperandrogenism-related illnesses. Nonetheless, this
short period was sufficient to observe the decreased incidence of symptoms such as
hirsutism, acne, or infertility and a significant increase in overall satisfaction.
These observed changes could be attributed to weight loss. While there was an
overall correlation between selected factors and measured hormones, it does not
allow us to draw clear conclusions regarding their causality and effectiveness. Some
limitations of our study warrant further discussion, such as the low participant
number, the lack of detailed biochemical parameters examination or the absence of
detailed endocrine profiles. However, referring to the work of other authors, we can
base the results of our study and conclude that lifestyle modifications should be
recommended in women with PCOS before conception [44]
[45]. Lifestyle factors, especially diet, are significant determinants of
many phenotypes. Importantly, these factors are modifiable and thus should be the
focus in efforts to lower the risk or should be considered as the primary early
management strategy. The results from this study indicate that interventions that
modify diet quality (e. g., low-calorie and low-fat diet) and enhanced
levels of physical activity can delay or prevent the onset of hyperandrogenism.
Conclusions
To sum up, in overweight and obese women, a proper selection of diet, introduction of
moderate physical activity, and reduction of weight, stress factors, and alcohol
consumption translates into several positive effects, in the form of reducing
symptoms of acne, hirsutism, menstrual disorders, and infertility. Healthy dietary
patterns, such as a diet with a low glycemic index, diet interventions including
low-calorie and low-fat diets, combined diet, and physical activity interventions,
should be promoted at both individual and population levels to prevent and reduce
the burden of hyperandrogenism in the future. None of the currently performed
studies have been conducted for a period longer than 1-year; therefore, subsequent
studies should focus on the long-term assessment of the impact of the low-IG diet on
the parameters we observed.
Availability of Data and Materials
Availability of Data and Materials
The datasets used and/or analyzed during the current study are available from
the corresponding author upon reasonable request.
Declarations
Ethics approval and consent to participate
All samples and archived data were obtained with full and informed patient
consent, and all experiments followed the ethical principles outlined by the
1964 Helsinki Declaration and ethical standards. This study was approved by the
Jagiellonian University Medical College Bioethics Committee (number
1072.6120.382.2020).
