doi:10.1111/jog.14650 J. Obstet. Gynaecol. Res. Vol. 47, No.

3: 1145–1152, March 2021

Ketogenic diet in women with polycystic ovary syndrome

and liver dysfunction who are obese: A randomized, open-
label, parallel-group, controlled pilot trial

Jian Li1, Wen-Pei Bai1 , Bo Jiang2, Le-Ran Bai3, Bei Gu1, Shu-Xiang Yan1, Fu-Ying Li1
and Bin Huang1
1
Department of Obstetrics and Gynecology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
2
Department of Gliomatology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
3
Department of Food Nutrition and Safety, Dalian Medical University, Dalian, China

Abstract
Aim: To evaluate the effect of a ketogenic diet (KD) in women with polycystic ovary syndrome (PCOS) and
liver dysfunction who were obese.
Methods: Women with PCOS and liver dysfunction who were obese were enrolled in this prospective,
open-label, parallel-group, controlled pilot trial, and randomly received KD (KD group) or conventional
pharmacological treatment (Essentiale plus Yasmin, control group) in a 1:1 ratio for 12 weeks. The primary
endpoint was the liver function markers. Secondary endpoints included the menstrual cycle, anthropometric
characteristics, body composition, hormonal levels, and metabolic biomarkers.
Results: Of the 20 eligible participants enrolled, 18 participants completed the study. The KD group
reported a significant reduction in anthropometric characteristics and body composition from baseline to
week 12 (all p < 0.05). In addition, there were significant reductions in menstrual cycle, plasma estradiol,
and progesterone levels in two groups (all p < 0.05), but no significant between-group difference was
observed. KD significantly reduced the liver function markers compared with control group (p < 0.05). The
signs of fatty liver disappeared in six out of seven fatty liver participants in KD group after 12 weeks of
intervention, while only one of 10 fatty liver participants in control group disappeared.
Conclusions: In addition to improving the menstrual cycle, KD had the additional benefits of reducing
blood glucose and body weight, improving liver function, and treating fatty liver compared to traditional
pharmacological treatment in women with PCOS and liver dysfunction who were obese.
Key words: fatty liver, ketogenic diet, liver dysfunction, obesity, polycystic ovary syndrome.

Introduction characterized by hyperandrogenism, menstrual dys-

function, polycystic ovaries, anovulatory infertility,
Polycystic ovary syndrome (PCOS) is a common and obesity.2,3 Oral contraceptives are the most com-
endocrine and metabolic disorder that affects at least mon treatment for woman with PCOS who do not
5%–15% of women of reproductive age.1 It is seek pregnancy.4 However, many patients with PCOS

Received: September 15 2020.

Accepted: December 25 2020.
Correspondence: Wen-Pei Bai, Department of Obstetrics and Gynecology, Beijing Shijitan Hospital, Capital Medical University, No.10,
Tieyi Road, Yangfangdian Street, Haidian District, Beijing 100038, China.
Email: baiwp@bjsjth.cn
Bo Jiang, Department of Gliomatology, Beijing Shijitan Hospital, Capital Medical University, No.10, Tieyi Road, Yangfangdian Street,
Haidian District, Beijing, 100038, China.
Email: jiangboprof@163.com

© 2021 Japan Society of Obstetrics and Gynecology 1145

J. Li et al.
present some relative contraindications to the use of
oral contraceptives.4,5 Previous study has showed that
up to 30% of patients with PCOS have elevated ala-
nine transaminase (ALT) levels, and the prevalence of
nonalcoholic fatty liver disease is 42% in a series of
patients with PCOS with an average age of
25 years.6,7 However, there is currently no specific
clinical treatment for patients with PCOS and liver
dysfunction. Thus, developing new treatment strate-
gies has become an urgent problem for patients with
PCOS and liver dysfunction.
Ketogenic diet (KD) is a high-fat and low-
carbohydrate diet that can lead to nutritional ketosis
and has been used to treat refractory epilepsy.8 Evi-
dence has showed that the use of the KD has been an
alternative or additional therapy in variety of cancers,
PCOS, neurological diseases, and acne.9 Mavropoulos
et al have reported that KD significantly improved
the body weight, LH/FSH ratio, and fasting insulin in
patients with PCOS and obesity.10 However, the role
of KD in patients with PCOS and liver dysfunction
who are obese remains unclear. Interestingly, evi-
dence has shown that KD is an effective treatment for
nonalcoholic fatty liver disease (NAFLD).11 This sug-
gests that KD may play an important role in patients
with PCOS and liver dysfunction who are obese.
Therefore, this pilot study investigated the effect of a
KD in women with PCOS and liver dysfunction who
were obese.
Methods
Study design and participants
This prospective, randomized, open-label, parallel-
group, controlled pilot trial enrolled women with
PCOS and liver dysfunction who were obese from
July 2019 to December 2019. The diagnosis of PCOS
was based on the revised Rotterdam Criteria [at least
two of three between oligo- or anovulation, clinical
and/or biochemical signs of hyperandrogenism and
polycystic ovaries (PCO), and exclusion of other etiol-
ogies (congenital adrenal hyperplasia, androgen-
secreting tumors, Cushing’s syndrome)].12 This trial
(Chinese Clinical Trial Registry, ChiCTR1900023979)
was conducted in accordance with Declaration of Hel-
sinki and Good Clinical Practice Guidelines and
approved by ethics committee of Beijing Shijitan Hos-
pital, Capital Medical University (number 2018-19).
Written informed consent was obtained from all
participants.
1146
The participants inclusion criteria were as follows:
(1) participants diagnosed with PCOS; (2) participants
aged 18–50 years; (3) participants with body mass
index (BMI) 28 kg/m2-32 kg/m2; (4) participants with
liver dysfunction [alanine aminotransferase (ALT)
and/or aspartate aminotransferase (AST) levels rise
above the upper limits of normal (ULN); AST and/or
ALT≥1.5 × ULN]; (5) participants without fertility
requirements within 3 months. The participants exclu-
sion criteria were as follows: (1) participants had a
history of excessive drinking (drinking>40 g ethanol/
week); (2) participants with a history of drug abuse;
(3) participants with hepatic tumor; (4) participants
with hepatic cirrhosis, viral hepatitis, or acute hepati-
tis; (5) pregnant or lactating women.
Intervention
All eligible subjects were randomly assigned to a KD
group or control group in a 1:1 ratio by the random
number created by a computer-generated coding sys-
tem (Figure 1). The KD in the present study consisted
of approximately 5%–10% of energy from carbohy-
drate (≤50 g/day), 18%–27% from protein, and 70%–
75% from fat. The daily calories were calculated by a
qualified dietitian based on the basic metabolic rate of
the women’s body composition analysis, which was
about 1300–1500 kcal/day. Subsequently, this daily
caloric requirement was divided into three-meal
menus, which were provided to participants through
mobile phones and updated every 3 days. Foods
appropriate for KD included all kinds of oils, all kinds
of meat (such as pork, beef, and fowl), eggs, seafood,
and vegetables (such as wax gourd, tomato, eggplant,
Brassica pekinensis, and garlic sprout). Participants
were allowed to eat with no limits wax gourd and
konjac products (such as konjac knot) as they con-
tained almost no carbohydrates. During the 12-week
intervention, the subjects were contacted by mobile
phone to ensure compliance and to address any
issues. Compliance with the dietary regimen was
monitored by taking daily measurements of urinary
ketones.
The control group was treated with polyene phos-
phatidylcholine capsule (Essentiale, Sanofi-Aventis
Pharmaceutical Co., Ltd). Essentiale was an oral drug
for auxiliary improve toxic liver damage (induced by
drugs, poisons, chemicals, and so on) approved by
China Food and Drug Administration and the Chi-
nese pharmacopeia.13 After liver function was normal,
oral contraceptives (Yasmin, Schering AG, Berlin, Ger-
many) were given to regulate menstruation. All
© 2021 Japan Society of Obstetrics and Gynecology

FIGURE 1 Study design.
*Anthropometric mea-
surement, body compo-
sition analysis, blood
tests, and ultrasonogra-
phy; KD, ketogenic diet
participants were required to perform resistance exer-
cises (15 min each time) three times a week to main-
tain bone density and muscle mass. Heavy aerobic
exercise was not recommended.
Outcome measures
All subjects underwent a detailed anthropometric
measurement (body weight, height, BMI), body com-
position analysis, blood tests (liver function markers,
hormonal levels, and metabolic biomarkers), and
ultrasonography (liver ultrasound and pelvic ultra-
sound) at baseline, week 4, and week 12. The primary
endpoint was the liver function markers. Secondary
endpoints included the menstrual cycle, anthropomet-
ric measurement, endocrine biomarkers, and meta-
bolic biomarkers.
Body weight was measured on the same scale with
the subject wearing light clothing but with shoes and
socks removed. Height was measured using a wall-
mounted Harpenden portable stadiometer (Holtain
Ltd, UK). Body composition such as body fat (BF),
body fat percentage (BFP), visceral fat area (VFA),
and waist-hip ratio (WHR) was analyzed by Bio
Impedance Analyzer BIA (Inbody 770, Inbody Co,
Seoul, Korea).
Menstrual cycle was defined as the number of days
from the onset of menstrual bleeding in one cycle to
the first day of the next. The menstrual cycle of partic-
ipants at baseline was defined as the average men-
strual cycle for 6 months before the intervention.
Blood tests were carried out after a 12 h fast, includ-
ing follicle-stimulating hormone (FSH), luteinizing
hormone (LH), estradiol (E), testosterone (T), proges-
terone (P), prolactin (PRL), ALT, AST, total cholesterol
© 2021 Japan Society of Obstetrics and Gynecology
KD in PCOS and liver dysfunction
(T-CHOL), triglyceride (TRIG), high density lipopro-
tein (HDL), low density lipoprotein (LDL), and blood
glucose (GLU). Blood samples used to assess ovarian
function (FSH, LH, E, T, P, and PRL) were collected at
the same phase of each subject’s menstrual cycle
(basal early follicular phase, day 3–5).
Liver ultrasound was performed in all subjects for
assessment of fatty liver. The hepatic fat accumula-
tion grade was calculated as follows: absent (score
0), mild (score 1), moderate (score 2), and severe
(score 3), according to the Hamaguchi score, which
uses a six-point scoring system based on hep-
atorenal echo contrast, liver brightness, deep attenu-
ation, and vascular blurring.14 Additionally, PCO
was identified on transvaginal pelvic ultrasound
(Logiq E8 with a 4–9 MHz electronic probe; GE
Medical Systems, Milwaukee, WI, USA) by either
12 or more follicles with a 2–9 mm diameter, or
increased ovarian volume (>10 cm) in at least one of
the ovaries.
Statistical analysis
Quantitative data were expressed as means  stan-
dard deviations (SD). Qualitative data were
expressed as number and percentage. Student’s t-
test was used to compare differences in baseline
characteristics of two groups. A repeated-measures
analysis of variance (ANOVA) was performed to
investigate the time-course of the changes at pri-
mary endpoint and secondary endpoints within
each group and to compare those between two
groups. Statistical significance was set at p < 0.05.
All statistical analyzes were performed by using
SPSS version 22.0 (SPSS Institute, USA).
1147
J. Li et al.
FIGURE 2 Participants flowchart
Results
Baseline characteristics
Of the 20 eligible participants enrolled in this pilot
study, all participants were randomly assigned to a
KD group or control group (Figure 2). A total of
18 participants completed the study (KD group, n = 8;
control group, n = 10). The reason for not completing
the study was withdrawn consent (unable to prepare
KD due to business travel, n = 2). The baseline charac-
teristics of included participants were showed in
Table 1. The two treatment groups were generally
well balanced for the age, height, BMI, and menstrual
cycle (all p > 0.05).
TABLE 1 Baseline characteristics of the participants
Characteristic
Age (year, mean  SD)
Weight (Kg, mean  SD)
Height (cm, mean  SD)
BMI (kg/m2, mean  SD)
Menstrual cycle (day, mean  SD)
Abbreviations: BMI, body mass index; KD, ketogenic diet; SD, standard deviations.
1148
Anthropometric characteristics and body
composition
As shown in Table 2, there were statistically signifi-
cant reductions in the BMI (from 32.81  3.75 to
28.33  2.62 kg/m2), body weight (from 87.19  11.14
to 75.41  8.01 kg), BF (from 35.38  7.97 to 28.57 
7.28 kg), BFP (from 40.34  5.37 to 34.04  3.74%),
VFA (from 128.91  34.93 to 97.78  26.43 cm2), and
WHR (from 0.93  0.05 to 0.88  0.04%) in KD group
from baseline to week 12 (all p < 0.05). However, no
statistic difference between the above indicators was
found in control group.
Hormonal levels and metabolic biomarkers
After 12 weeks of intervention, the menstrual cycles
were significantly shortened in two groups (p < 0.05),
but no statistical difference was observed between
two groups (Table 3). In addition, there were statisti-
cally significant reductions in plasma E and P levels
in two groups (p < 0.05), but no statistical difference
was observed between two groups.
Blood tests results also showed that there were no
significant within-group and between-group differ-
ences in T-CHOL, TRIG, HDL, and LDL levels from
baseline to week 12 in two groups (Table 3). How-
ever, a significant reduction in GLU level was
observed in KD group after 12 weeks of intervention.
Liver function markers
From baseline to week 12, plasma ALT in control
group decreased from 71.30  24.33 IU/L to
37.60  13.16 IU/L (p < 0.05), and AST decreased
from 47.43  23.43 IU/L to 28.00  6.41 IU/L
(p < 0.05) (Figure 3). In addition, there were statisti-
cally significant reductions in plasma ALT (from
71.63  27.76 to 22.01  9.50 IU/L) and AST (from
46.10  16.29 to 18.78  5.95 IU/L) in KD group (all
p < 0.05). Moreover, the plasma ALT and AST of KD
group at 12 weeks was significantly lower than that
in control group (p < 0.05), suggesting the superiority
Control group (n = 10) KD group (n = 8) p-value
28.90  4.93 31.13  3.64 0.304
74.62  8.23 87.19  11.14 0.014
158.00  6.39 163.00  4.31 0.159
32.81  3.75 29.82  2.36 0.056
63.00  19.75 72.50  33.17 0.757
© 2021 Japan Society of Obstetrics and Gynecology
 KD in PCOS and liver dysfunction

of KD than conventional treatment in improving liver

Abbreviations: BF, body fat; BFP, body fat percentage; BMI, body mass index; KD, ketogenic diet; VFA, visceral fat area; WHR, waist-hip ratio; aVersus baseline, p > 0.05; bVersus
97.78  26.43b, c
function.

28.33  2.62b, c
75.41  8.01b, c

28.57  7.28b, c
34.04  3.74b, c

0.88  0.04b, c
Ultrasound evaluation outcomes

Week 12
Before treatment, eight participants in control group
were found to have bilateral PCO and one has unilat-
eral PCO, and six participants in KD group were
bilateral PCO, two participants were unilateral PCO.
81.84  10.99b, c

113.13  31.32b, c
31.51  7.78d, c
30.77  3.62b, c

37.51  4.65b, c

0.90  0.04b, c
After 12 weeks of intervention, PCOS signs in one
patient with unilateral PCO disappeared in control
group and two participants with bilateral PCO dis-
Week 4

appeared in KD group.
Liver ultrasound results showed that the fatty liver
signs only in one of 10 participants with fatty liver in
TABLE 2 Changes in anthropometric characteristics and body composition variables after 12 weeks of intervention

87.19  11.14d

128.91  34.93d

the control group disappeared after 12 weeks of inter-

35.38  7.97d
40.34  5.37d

0.93  0.05d
32.81  3.75b

vention. However, the signs of fatty liver disappeared

KD group

in six out of seven fatty liver participants in KD group

Baseline

after 12 weeks of intervention.

Discussion
94.98  10.75a

PCOS was a common endocrine and metabolic disor-

29.20  2.24a
73.14  8.52a

24.85  3.93a
33.85  4.17a

0.87  0.02a

der in premenopausal women.15 Previous study had

Week 12

showed that approximately 30% of PCOS participants

had elevated ALT levels, and the prevalence of non-
alcoholic fatty liver disease was about 42%.6,7 KD was
control group, p > 0.05; cVersus baseline, p < 0.05 and dVersus control group, p < 0.05.

reported to play an important role in women with

96.09  12.75a

PCOS and obesity.10,16 However, there were few

29.64  2.65a
74.12  8.97a

25.28  4.18a
33.92  3.93a

0.87  0.02a

reports about the effect of a KD in women with PCOS

Week 4

and liver dysfunction. Therefore, the present study

aimed to investigate the effect of a KD in women with
PCOS and liver dysfunction who were obese.
Approximately half of women with PCOS were
Control group

96.01  10.70

more likely to be overweight or obese compared with

29.82  2.36
74.62  8.23

25.58  4.02
34.28  3.83

0.87  0.03

women without PCOS.17,18 A KD was regarded as an

Baseline

effective regimen for weight loss because of the ability

of ketone bodies in suppressing appetite and allowing
a very small calorie intake.19 In the present study, we
observed the similar weight loss effects of KD in
women with PCOS and liver dysfunction who were
Anthropometric characteristics

obese. However, no weight loss was found in the con-

trol group, suggesting KD had the additional benefits
in reducing body weight compared with traditional
pharmacological treatment. Although the menstrual
Body composition
BMI (kg/m2)

cycle in two groups was all significantly reduced after

Weight (kg)

VFA (cm2)

12 weeks of intervention. The menstrual cycle of par-

WHR (%)
BFP (%)
BF (kg)

ticipants in KD group returned to normal level at

4 weeks, while participants in control group returned
to normal level at 12 weeks. The possible reason was
that oral contraceptives were contraindicated in

© 2021 Japan Society of Obstetrics and Gynecology 1149

J. Li et al.

TABLE 3 Changes in endocrine and metabolic biomarkers after 12 weeks of intervention

Control group KD group
Baseline Week 4 Week 12 Baseline Week 4 Week 12
Menstrual cycle (day) 63.00  19.75 54.00  14.68 a
33.00  6.32 b
72.50  33.17 c
46.50  20.09 b,c
32.50  2.67b,c
Hormonal levels
FSH (IU/L) 5.67  2.27 5.83  1.70a 6.63  2.07a 6.46  1.65c 5.28  1.10a,c 6.90  2.55a,c
LH (IU/L) 8.92  5.18 6.04  2.28a 8.26  6.64a 11.13  9.02c 6.28  1.94a,c 10.37  14.27a,c
E (pmol/L) 76.29  78.47 42.80  17.56a 38.70  20.25a 84.13  101.93c 72.13  61.74a,c 68.25  65.08a,c
P (pmol/L) 3.63  6.89 0.64  0.42a 0.47  0.25a 0.81  0.90c 1.03  1.72a,c 0.50  0.34a,c
T (nmol/L) 0.73  0.13 0.61  0.16a 0.58  0.26a 0.67  0.16c 0.52  0.16a,c 0.46  0.21a,c
PRL (ng/mL) 9.02  2.13 9.67  4.60a 10.10  5.49a 13.18  7.92c 10.04  3.34a,c 11.59  8.05a,c
LH/FSH 1.61  0.58 1.04  0.26a 1.29  0.92a 1.58  0.76c 1.20  0.33a,c 0.86  0.32a,c
Metabolic biomarkers
T-CHOL (mmol/L) 4.99  0.74 5.02  0.62a 4.83  0.60a 5.28  0.99c 4.46  1.14a,c 4.77  1.22a,c
TRIG (mmol/L) 2.74  1.25 2.99  1.58a 3.14  2.42a 2.44  1.66c 1.59  0.85a,d 1.66  0.80a,c
HDL (mmol/L) 1.23  0.36 1.56  0.57a 1.25  0.41a 1.03  0.10c 0.97  0.10a,d 1.04  0.10a,c
LDL (mmol/L) 2.74  0.86 2.43  1.04a 2.52  0.84a 3.41  0.74c 2.69  1.00a,c 2.83  0.99a, b
GLU (mmol/L) 5.28  0.49 5.17  0.82a 5.12  0.58a 5.92  0.85c 5.22  0.67b,c 5.11  0.46b,c
Abbreviations: E, estradiol; FSH, follicle-stimulating hormone; GLU, blood glucose; HDL, high density lipoprotein; LDL, low density lipo-
protein; LH, luteinizing hormone; P, progesterone; PRL, prolactin; T, testosterone; T-CHOL, total cholesterol; TRIG, triglyceride; KD, keto-
genic diet; aVersus baseline, p > 0.05; bVersus baseline, p < 0.05; cVersus control group, p > 0.05 and dVersus control group, p < 0.05.

FIGURE 3 Changes in liver function after 12 weeks of intervention. ALT, alanine aminotransferase; AST, aspartate
aminotransferase; KD, ketogenic diet; * versus baseline, p < 0.05; #versus control group, p < 0.05. , Contro group;
, KD group

participants with abnormal liver function. For women
with liver dysfunction and PCOS, oral contraceptive
was given after liver function was normal. Therefore,
the menstrual recovery time in control group was lon-
ger than that in KD group in women with PCOS and
liver dysfunction who were obese.
ALT and AST were the key enzymes in the biologi-
cal processes and had been used as markers of liver
function.20 Reports had showed that their levels ele-
vated in different liver injures, such as hepatitis and
cirrhosis, which induced by alcohol, viruses, drugs,
and oxidative stress.21 In the present study, we found
that KD significantly reduced the ALT and AST levels
compared with control group after 12 weeks of inter-
vention. This was consistent with that reported by
Bruci, which showed that a very low-calorie KD
decreased AST and ALT levels in people with obesity
and mild kidney failure, despite not reaching signifi-
cance.22 Additionally, growing amount of evidence
showed that the prevalence of NAFLD in patients
with PCOS was significantly increased, and PCOS
may be a risk factor for NAFLD.23–25 About 40–50%
of patients with PCOS had hepatic steatosis on imag-
ing.26 In the present study, we found that 100%
(10/10) patients with PCOS had fatty liver in the con-
trol group and 87.5% (7/8) in the KD group. After

1150 © 2021 Japan Society of Obstetrics and Gynecology


12 weeks of intervention, the signs of fatty liver dis-
appeared in six out of seven participants with fatty
liver in KD group, while only one of 10 participants
with fatty liver in the control group disappeared.
These results indicated that KD had the additional
benefits of improving liver function and treating fatty
liver compared with traditional pharmacological
treatment in women with PCOS and liver dysfunction
who were obese.
There were several limitations in the current study.
Firstly, this trial was a pilot study with a small sample
size, which had certain limitations in clinical applica-
tion. Secondly, other comparative studies were
needed to determine whether these effects were due
to the specific dietary approach or weight loss. There-
fore, future studies with an appropriate sample size
should be conducted to investigate the effect of a KD
in women with PCOS and liver dysfunction who
were obese.
In addition to improving the menstrual cycle, KD
had the additional benefits of reducing blood glucose
and body weight, improving liver function, and
treating fatty liver compared to traditional pharmaco-
logical treatment in women with PCOS and liver dys-
function who were obese. A KD may be considered as
a valuable non pharmacological treatment for women
with PCOS and liver dysfunction who were obese.
Disclosure
The authors declare that they have no conflict of
interest.
Funding
This work was supported by Beijing Hospitals
Authority’ Ascent Plan [number DFL20190701].
Author Contributions
Conception and design: Bo Jiang, Jian Li, and Wen-Pei
Bai. Data collection: Jian Li and Le-Ran Bai; Data analy-
sis and interpretation: Jian Li. Providing materials and
samples: Bei Gu, Shu-Xiang Yan, Fu-Ying Li, Bin
Huang, and Le-Ran Bai. Drafting article: Jian
Li. Administrative support: Wen-Pei Bai. All the authors
have read and approved the final manuscript.
© 2021 Japan Society of Obstetrics and Gynecology
KD in PCOS and liver dysfunction
References
1. Morley LC, Tang T, Yasmin E, Norman RJ, Balen AH. Insu-
lin-sensitising drugs (metformin, rosiglitazone, pioglitazone,
D-chiro-inositol) for women with polycystic ovary syn-
drome, oligo amenorrhoea and subfertility. Cochrane Data-
base Syst Rev 2017; 11: Cd003053.
2. Kyselova A, Hinrichsmeyer H, Zukunft S et al. Association
between arginase-containing platelet-derived microparticles
and altered plasma arginine metabolism in polycystic ovary
syndrome. Metabolism 2019; 90: 16–19.
3. Ding D-C, Tsai I-J, Wang J-H, Lin S-Z, Sung F-C. Coronary
artery disease risk in young women with polycystic ovary
syndrome. Oncotarget 2018; 9: 8756.
4. Amiri M, Tehrani FR, Nahidi F, Kabir A, Azizi F,
Carmina E. Effects of oral contraceptives on metabolic pro-
file in women with polycystic ovary syndrome: a meta-
analysis comparing products containing cyproterone ace-
tate with third generation progestins. Metabolism 2017; 73:
22–35.
5. Spencer AL, Bonnema R, McNamara MC. Helping women
choose appropriate hormonal contraception: update on risks,
benefits, and indications. Am J Med 2009; 122: 497–506.
6. Goverde AJ, van Koert AJ, Eijkemans MJ et al. Indicators for
metabolic disturbances in anovulatory women with polycys-
tic ovary syndrome diagnosed according to the Rotterdam
consensus criteria. Hum Reprod 2009; 24: 710–717.
7. Cerda C, Pérez-Ayuso RM, Riquelme A et al. Nonalcoholic
fatty liver disease in women with polycystic ovary syn-
drome. J Hepatol 2007; 47: 412–417.
8. Gupta L, Khandelwal D, Kalra S, Gupta P, Dutta D,
Aggarwal S. Ketogenic diet in endocrine disorders: Current
perspectives. J Postgrad Med 2017; 63: 242.
9. Li
skiewicz D, Liskiewicz A, Nowacka-Chmielewska M et al.
Brain macroautophagy on the ketogenic diet. Proc Nutr Soc
2020; 79 (OCE2). https://www.cambridge.org/core/journals/
proceedings-of-the-nutrition-society/article/brain-macroautop
hagy-on-the-ketogenic-diet/D2556BAE50B89288C0AE7A21AF
CE77F8.
10. Mavropoulos JC, Yancy WS, Hepburn J, Westman EC. The
effects of a low-carbohydrate, ketogenic diet on the polycys-
tic ovary syndrome: a pilot study. Ann Nutr Metab 2005;
2: 35.
11. Luukkonen PK, Dufour S, Lyu K et al. Effect of a ketogenic
diet on hepatic steatosis and hepatic mitochondrial metabo-
lism in nonalcoholic fatty liver disease. Proc Natl Acad Sci U
S A 2020; 117: 7347–7354.
12. Revised 2003 consensus on diagnostic criteria and long-term
health risks related to polycystic ovary syndrome. Fertil Ste-
ril 2004; 81: 19–25.
13. Naiqiong W, Liansheng W, Zhanying H et al. A multicenter
and randomized controlled trial of bicyclol in the treatment
of statin-induced liver injury. Med Sci Monit 2017; 23:
5760–5766.
14. Hamaguchi M, Kojima T, Itoh Y et al. The severity of ultra-
sonographic findings in nonalcoholic fatty liver disease
reflects the metabolic syndrome and visceral fat accumula-
tion. Am J Gastroenterol 2007; 102: 2708–2715.
15. Escobar-Morreale HF. Polycystic ovary syndrome: defini-
tion, aetiology, diagnosis and treatment. Nat Rev Endocrinol
2018; 14: 270–284.
1151
J. Li et al.
16. Paoli A, Mancin L, Giacona MC, Bianco A, Caprio M. Effects
of a ketogenic diet in overweight women with polycystic
ovary syndrome. J Transl Med 2020; 18: 104.
17. Panico A, Messina G, Lupoli GA et al. Quality of life in over-
weight (obese) and normal-weight women with polycystic
ovary syndrome. Patient Prefer Adherence 2017; 11: 423–429.
18. Lim S, Smith CA, Costello MF, MacMillan F, Moran L, Ee C.
Barriers and facilitators to weight management in over-
weight and obese women living in Australia with PCOS: a
qualitative study. BMC Endocr Disord 2019; 19: 106.
19. Perticone M, Maio R, Sciacqua A et al. Ketogenic diet-
induced weight loss is associated with an increase in vitamin
D levels in obese adults. Molecules (Basel, Switzerland) 2499;
24: 2019.
20. Lieberman HR, Kellogg MD, Fulgoni VL III, Agarwal S.
Moderate doses of commercial preparations of Ginkgo biloba
do not alter markers of liver function but moderate alcohol
intake does: A new approach to identify and quantify bio-
markers of ‘adverse effects’ of dietary supplements. Regul
Toxicol Pharmacol 2017; 84: 45–53.
21. Concepción Navarro M, Pilar Montilla M, Martín A,
Jiménez J, Pilar Utrilla M. Free radical scavenger and
1152
antihepatotoxic activity of Rosmarinus tomentosus. Planta
Med 1993; 59: 312–314.
22. Bruci A, Tuccinardi D, Tozzi R et al. Very low-calorie keto-
genic diet: a safe and effective tool for weight loss in
patients with obesity and mild kidney failure. Nutrients
2020; 12: 333.
23. Wu J, Yao XY, Shi RX, Liu SF, Wang XY. A potential link
between polycystic ovary syndrome and non-alcoholic fatty liver
disease: an update meta-analysis. Reprod Health 2018; 15: 77.
24. Cai J, Wu CH, Zhang Y et al. High-free androgen index is
associated with increased risk of non-alcoholic fatty liver
disease in women with polycystic ovary syndrome, indepen-
dent of obesity and insulin resistance. Int J Obes 2017; 41:
1341–1347.
25. Rocha ALL, Faria LC, Guimar~ aes TCM et al. Non-alcoholic
fatty liver disease in women with polycystic ovary syn-
drome: systematic review and meta-analysis. J Endocrinol
Invest 2017; 40: 1279–1288.
26. Sarkar M, Terrault N, Duwaerts CC, Tien P, Cedars MI,
Huddleston H. The association of hispanic ethnicity with
nonalcoholic fatty liver disease in polycystic ovary syn-
drome. Curr Opin Obstet Gynecol 2018; 1: 24–33.
© 2021 Japan Society of Obstetrics and Gynecology