doi:10.1111/jog.15006 J. Obstet. Gynaecol. Res. Vol. 47, No.

11: 3895–3902, November 2021

Reproductive prognosis of patients with hypogonadotropic

hypogonadism: Retrospective review of 16 cases with
amenorrhea

Aki Oride , Haruhiko Kanasaki , Hiroe Okada and Satoru Kyo

Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo, Japan

Abstract
Aim: The aim of this study was to evaluate the general characteristics, menstruation status, and fertility
outcomes of patients with hypogonadotropic hypogonadism (HH).
Methods: We evaluated 16 patients with HH who visited our institution between April 2012 and March
2016 with a complaint of amenorrhea.
Results: Four (25%) patients had primary amenorrhea and the remaining 12 (75%) cases had secondary
amenorrhea. Among the patients with primary amenorrhea, weight loss was considered to be the underlying
cause in one (25%) patient, whereas the remaining three (75%) cases were idiopathic HH. Among HH cases
with secondary amenorrhea, six (50%) developed amenorrhea following weight loss, whereas the remaining
six cases were of unknown etiology. Among the 16 patients with HH, we observed the sporadic restart of
the menstrual cycle in four (25%) women during follow-up. Infertility treatment was administered to nine
patients with HH who wished to become pregnant. Clomiphene citrate was effective in four patients with
secondary amenorrhea and induced follicular development. Seven of nine patients with HH (77.8%) became
pregnant following infertility treatment. In some cases of HH, the serum levels of gonadotropin increased
sporadically during follow-up, regardless of the recovery of menstruation. We followed one patient with
HH for more than 20 years. Although her gonadotropin levels were generally low and sometimes fluctuated
without spontaneous menstruation, they increased dramatically to menopausal levels at 50 years of age.
However, they again decreased to hypogonadotropic levels.
Conclusion: As the pathophysiology varied widely among patients, the etiologic factors underlying HH
might also vary.
Key words: amenorrhea, hypogonadotropic hypogonadism, infertility.

Introduction pituitary gland.1 Pituitary gonadotropins stimulate

The reproductive function of women is principally
controlled by the hypothalamic–pituitary–gonadal
axis. Gonadotropin-releasing hormone (GnRH) is
released into the hypophyseal portal circulation from
the hypothalamus in a pulsatile manner and regulates
the secretion of gonadotropins, luteinizing hormone
(LH), and follicle-stimulating hormone (FSH) from the
follicular growth, oocyte maturation, and sex steroid
synthesis in the gonads.2
Hypogonadotropic hypogonadism (HH) is caused
by dysfunction of the hypothalamus, which involves
kisspeptin and GnRH neurons, or the hyposecretion
of gonadotropins due to dysfunction of the pituitary
gland. HH has been classified as a Group I
anovulation disorder by the World Health

Received: May 10 2021.

Accepted: August 24 2021.
Correspondence: Haruhiko Kanasaki, Department of Obstetrics and Gynecology, Faculty of Medicine, Shimane University, 89-1
Enya-cho, Izumo, Shimane 693-8501, Japan. Email: kanasaki@med.shimane-u.ac.jp

© 2021 Japan Society of Obstetrics and Gynecology. 3895


Oride et al.
Organization3 and is characterized by low gonadotro-
pin levels and estrogen deficiency. If amenorrhea
develops in cases with HH after previously routine
menstrual cycles, it is defined as a severe form of
functional hypothalamic amenorrhea. In most cases,
HH is caused by psychogenic stress, weight changes,
undernutrition, or excessive exercise.4 In contrast,
cases with HH induced by GnRH deficiency exhibit
primary amenorrhea with absent or incomplete
pubertal development, which is called congenital HH
(CHH) and is a genetically heterogeneous disorder.5
The terms “CHH” and “idiopathic HH” are used
almost interchangeably. Kallmann syndrome is one
manifestation of CHH and is accompanied by a
reduced sense of smell.6 CHH is classified into two
groups: one involving mutations in genes regulating
the migration of GnRH neurons (most of which
induce Kallmann syndrome) and another involving
mutations in genes regulating GnRH secretion, such
as kisspeptin.7
Given the low incidence of HH, a limited number
of studies have evaluated the outcome or prognosis.
A study following patients with functional hypotha-
lamic amenorrhea (not focused on HH) reported that
the natural menstrual cycle was recovered in approxi-
mately 70% of these patients.8 Interestingly, even in
male patients with CHH who exhibit infertility, cases
with sustained recovery of reproductive function are
also noted.9,10
In this study, we retrospectively reviewed 16 female
patients with HH who visited our institution from
April 2012 to March 2016. Etiologic factors and
menstruation status were summarized. In addition,
the fertility outcomes of patients with HH who
wished to become pregnant were retrospectively
reviewed. Furthermore, we described cases of HH
whose gonadotropin levels were monitored for more
than 5 years.
Materials and Methods
Patients
Because the measurement system for hormone levels
differs among institutions, international criteria for
HH with a cutoff value for gonadotropin levels do
not exist. In this study, HH was defined according to
the following criteria: (i) primary or secondary amen-
orrhea for at least 3 months; (ii) serum estradiol
<20 pg/mL; (iii) serum LH and/or FSH <3.0 IU/mL;
and (iv) no organic disease of the uterus, ovary, or
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central nervous system. The cutoff value for gonado-
tropins was defined according to the normal range
using our measurement system. Cases with adrenal
gland disease, thyroid disease, anorexia nervosa, or
drug-induced amenorrhea were excluded. From April
2012 to March 2016, 16 patients who visited Shimane
University Hospital with a complaint of amenorrhea
satisfied these criteria. We retrospectively reviewed
the medical records of patients to determine age, men-
strual history, body mass index, etiologic factors, lab-
oratory data, and the course of medical treatment.
The reproductive outcomes of nine patients with HH
who received infertility treatment were also evalu-
ated. Ethical approval for this study was obtained
from the Ethical Committee of Shimane University
Hospital (20161220-2).
Blood sampling and hormone assay
Blood samples were collected at each patient’s initial
visit. The serum levels of LH, FSH, and estradiol were
measured, and prolactin, testosterone, dehydroepian-
drosterone-sulfate, thyroid-stimulating hormone, triiodo-
thyronine, and thyroxin levels were determined to rule
out the presence of other endocrine diseases. Serum
levels of LH, FSH, estradiol, prolactin, thyroid-
stimulating hormone, free-triiodothyronine, and
free-thyroxin were determined in our hospital by fluo-
rescence immunoassays using an automated immunoas-
say analyzer (Tosoh Bioscience, Tokyo, Japan).
Testosterone and dehydroepiandrosterone-sulfate levels
were measured by electrochemiluminescence immunoas-
says by SRL, Inc. (Tokyo, Japan).
Infertility treatment
Hormone replacement therapy (HRT) was given to
patients who had no wish to conceive. Infertility treat-
ment was administered to patients with HH who
wished to become pregnant. After male infertility fac-
tors were ruled out, we prescribed 100 mg/day clomi-
phene citrate (CC) as the first-line therapy from
5 days after the end of menstrual bleeding. Generally,
CC is considered ineffective in patients with hypo-
estrogenic amenorrhea; however, we noticed that CC
was effective in some HH cases at our institution.
Owing to its convenience compared with injections,
CC is routinely used as a first-line treatment at our
institution. If follicles developed following CC admin-
istration, the couples were advised on the optimal
timing of sexual intercourse after the injection of
5000 IU human chorionic gonadotropin to induce
ovulation. If CC treatment did not induce follicle
© 2021 Japan Society of Obstetrics and Gynecology.
 14470756, 2021, 11, Downloaded from https://obgyn.onlinelibrary.wiley.com/doi/10.1111/jog.15006 by Teesside University Library & Information Services, Wiley Online Library on [22/10/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Sixteen hypogonadotropic hypogonadism cases

development, gonadotropin treatment, such as human
menopausal gonadotropin (hMG) or recombinant
FSH (recFSH), was chosen as a second-line therapy.
recFSH was applied only when patients requested
self-injection because it is the only product approved
for self-injection in Japan. After repeated failures of
CC or hMG/recFSH treatment or at the patient’s
request, in vitro fertilization (IVF)-embryo transfer
(ET) was initiated. A long or short protocol using a
GnRH agonist or a GnRH antagonist protocol was
applied to each patient according to their requests or
at the physician’s discretion. All patients received
150–300 IU hMG daily until at least two dominant fol-
licles became ≥18 mm in diameter. Human chorionic
gonadotropin (10 000 IU) was then administered
intramuscularly, followed by transvaginal oocyte
retrieval after 36 h. After the IVF/intra-cytoplasmic
sperm injection procedure, early embryos on Day 3 or
blastocysts on Day 5 or 6 after ovum pick-up were
cryopreserved, and frozen–thawed embryo or blasto-
cyst transfer was performed following HRT in all
cases.
Results
Basal characteristics of 16 patients with HH
Sixteen patients satisfied our HH criteria during the
study period. Table 1 shows the baseline characteris-
tics of the patients at their first visit. The median age
was 25.35  6.64 years (range, 15–35 years). The aver-
age body mass index was 18.52  2.71. Four patients
complained of primary amenorrhea and the
remaining 12 patients had secondary amenorrhea for
at least 3 months. Serum LH levels were generally
low (<1.0 mIU/mL), except for Cases 4 and 9. Serum
FSH levels were also low. Circulating estradiol
(E2) levels were less than 10 pg/mL in 10 of
16 patients with HH, with low levels in the remaining
six women. Among four patients with primary amen-
orrhea, one had a history of weight loss in the previ-
ous 3 years (Case 2). In the other three cases of
primary amenorrhea, there was no history explaining
the cause of HH and all had a normal sense of smell.
Among the 12 patients with secondary amenorrhea,
six had a history of severe weight loss in the previous
3 years and the remaining six cases did not have any
obvious cause of HH. Gonadotropin and E2 levels
were generally low in all cases of HH with secondary
amenorrhea (Table 1).
Recovery of spontaneous menstrual bleeding in
patients with HH
Infertility treatment was administered to patients who
wished to become pregnant. Otherwise, HRT was cho-
sen for patients with amenorrhea. Kaufmann therapy
using conjugated estrogens (1.25 mg) and
medroxyprogesterone acetate (10 mg) was applied to
each patient with HH as HRT. Even when patients
received HRT, medication was occasionally discontinued

TABLE 1 Overview of the patients with HH

Age at Restart of
Case first visit LH FSH E2 spontaneous Response
Amenorrhea no. (years) BMI (mIU/mL) (mIU/mL) (pg/mL) Cause menstruation to CC
Primary 1 19 24.8 0.1 <0.5 <10 ▯ -
2 19 16.4 0.1 <0.5 <10 Weight loss ▯ -
3 18 20.5 0.1 <0.5 <10 ▯ 
4 16 17.1 2 6.6 51 ▯ -
Secondary 5 32 16.8 0.1 7.3 23 Weight loss 
6 27 18.9 0.1 0.9 <10 ▯ -
7 26 15.6 0.1 <0.5 25 ▯ 
8 26 18.4 0.2 3.4 <10 Weight loss ▯ ▯
9 16 19.5 2.2 7.2 30 ▯ ▯ -
10 35 18.9 0.1 <0.5 <10 Weight loss ▯
11 32 17.4 0.8 5.5 15 ▯ 
12 15 15.8 0.1 <0.5 <10 Weight loss -
13 29 17 0.7 6.4 13 Weight loss 
14 32 24.1 0.3 2.8 <10 ▯ -
15 31 18.2 0.1 <0.5 <10 ▯ ▯ ▯
16 33 14.7 0.1 <0.5 <10 Weight loss ▯
Abbreviations: BMI, body mass index; CC, clomifene citrate; E2, estradiol; FSH, follicle-stimulating hormone; HH, hypogonadotropic hyp-
ogonadism; LH, luteinizing hormone.

© 2021 Japan Society of Obstetrics and Gynecology. 3897


Oride et al.
for 3 months to assess whether menstruation recovered
spontaneously. Spontaneous recovery of menstrual
bleeding was observed in four of 16 HH cases. Men-
strual bleeding recovered spontaneously in one case
with weight loss-related primary amenorrhea after dis-
continuing HRT following weight gain. Among the
12 cases of secondary amenorrhea, spontaneous men-
struation returned in three women during follow-up.
Regular menstrual cycles restarted in one patient after
returning to her usual weight. We also observed the
recovery of menstrual bleeding in two cases whose
cause of secondary amenorrhea was unknown (Table 1).
Effect of CC on HH
Nine of 16 patients with HH wished to become preg-
nant and received infertility treatment. We routinely
prescribe CC as the initial treatment for infertility. CC
(100 mg/day) was given for 5 days to nine patients
with HH, including one case with primary amenor-
rhea and eight cases with secondary amenorrhea.
Although CC was not effective in the single patient
with HH with primary amenorrhea, follicles devel-
oped in four of eight patients with HH with second-
ary amenorrhea in response to the oral administration
of CC. A response to CC was observed in three of five
HH cases whose cause was weight loss and one of
three cases whose cause was undetermined (Table 2).
Reproductive outcomes by infertility treatment in
patients with HH
Among nine patients who received infertility treat-
ment, including oral CC administration, seven
became pregnant. One patient with HH with primary
amenorrhea became pregnant by IVF-ET treatment
following hMG treatment. Eight patients with HH
with secondary amenorrhea underwent infertility
treatment, and six became pregnant. Two cases whose
TABLE 2 Effect of CC administration in nine HH
patients who wanted to become pregnant
Nine cases/
total 16 HH cases
Follicles
Desire for child developed
CC administration 9 4
Primary amenorrhea 1 0
Secondary amenorrhea 8 4
Weight loss 5 3
Cause unknown 3 1
Abbreviations: CC, clomifene citrate; HH, hypogonadotropic
hypogonadism.
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cause was weight loss became pregnant following
oral CC administration and timing advice, whereas
the remaining four cases (weight loss, two; unknown
cause, two) became pregnant after receiving IVF-ET
treatment (Table 3).
Changes in serum levels of gonadotropins in four
cases followed up for more than 5 years
We observed four patients with HH for more 5 years
from their initial visit. The changes in gonadotropin
levels in these four women according to their age are
shown in Table 4. Case 1 had HH with primary
amenorrhea. During a follow-up period of 7 years,
her gonadotropin levels were consistently low and
menstruation did not recover spontaneously when
HRT was intermittently stopped to evaluate her men-
struation status. Case 2 had HH with primary amen-
orrhea following a history of weight loss. Her FSH
serum levels increased at 20 years of age, and her
menstrual cycle recovered spontaneously after weight
gain at this age. Case 15 had HH with secondary
amenorrhea of unknown etiology. Her serum gonado-
tropin levels increased after 34 years of age. At
35 years of age, her menstrual cycle recovered sponta-
neously after HRT was discontinued. Case 16 had HH
with secondary amenorrhea and was observed for
more than 20 years. She had low gonadotropin levels
when she was 33 years of age and received infertility
treatment because she wished to become pregnant.
Her basal levels of LH and FSH were generally low,
but they fluctuated during infertility treatment. She
became pregnant by IVF-ET but had a miscarriage.
She discontinued infertility treatment at 42 years of
age, and HRT was continued afterward. Interestingly,
her gonadotropin levels increased dramatically when
she was 50 years of age. Her LH and FSH serum
levels were 62.4 and 165.4 mIU/mL, respectively,
TABLE 3 Reproductive outcome and infertility treat-
ment in nine patients who wished to become
pregnant
Achieve pregnancy 7/9
No
effect Primary amenorrhea 1/1
hMG/IVF-ET 1
5 Secondary amenorrhea 6/8
1 Weight loss CC+ timing advice 2
4 hMG/IVF-ET 2
2 Unknown cause hMG/IVF-ET 2
3
Abbreviations: CC, clomifene citrate; HH, hypogonadotropic
hypogonadism; hMG, human menopausal gonadotropin; IVF-
ET, in vitro fertilization-embryo transfer.
© 2021 Japan Society of Obstetrics and Gynecology.

TABLE 4 Changes in gonadotropin levels according to age in four patients with HH
Note: Arrows indicate the years when spontaneous menstrual bleeding was observed after the discontinuation of HRT therapy. and
Abbreviations: E2, estradiol; FSH, follicle-stimulating hormone; LH, luteinizing hormone.
which were close to postmenopausal levels. Surpris-
ingly, her serum gonadotropin levels decreased again
to HH levels when she was 54 years of age (Table 4).
Discussion
Here, we described female patients with HH who
were referred to our institution because of amenor-
rhea. Although gynecologists sporadically encounter
this rare disease, to our knowledge there are few ana-
lyses of the outcomes of patients with HH in Japan.
We observed only 16 cases with extremely low serum
levels of FSH and LH between April 2012 and March
2016. Although we treat a large number of patients
with amenorrhea, cases with very low circulating
gonadotropin (LH and/or FSH <3.0 IU/mL) and
estradiol (<20 pg/mL) levels are rare. We classified
these patients into two groups: HH with primary
amenorrhea (four cases) and HH with secondary
amenorrhea (12 cases). We did not evaluate genetic
factors, which might contribute to the pathogenesis.
Although one patient with primary amenorrhea had a
history of severe weight loss, we classified this case as
© 2021 Japan Society of Obstetrics and Gynecology.
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Sixteen hypogonadotropic hypogonadism cases
primary amenorrhea with HH; however, it is still
unclear whether severe weight loss caused primary
amenorrhea with low gonadotropins. Without a his-
tory of weight loss, this patient might have been clas-
sified as absent menstruation, as occurs in CHH. In
contrast, patients with HH and secondary amenor-
rhea experience a normal onset of puberty, with a sec-
ondary change to hypogonadism by several
mechanisms. In our 12 cases of HH with secondary
amenorrhea, six developed amenorrhea after drastic
weight loss, whereas no obvious causes were identi-
fied in the other six patients. Because some menstrual
bleeding is observed in <10% of congenital cases,11
some idiopathic cases with secondary amenorrhea
might be included in CHH with primary amenorrhea.
Among 16 patients with HH, spontaneous menstru-
ation was initiated or recovered in four cases during
follow-up. Because the follow-up period differed
among patients, we could not determine the recovery
rate of menstruation in patients with HH. However, it
was surprising that menstruation started even in a
patient with primary amenorrhea with very low
gonadotropin levels. In addition, we observed the
recovery of menstruation in three HH cases with
3899

Oride et al.
secondary amenorrhea. It is understandable that men-
struation restarted after weight gain; however, menstrual
cycles restarted unexpectedly in the remaining two
women with HH of unknown etiology. We did not
follow-up all of the HH cases for a long period of time,
and we did not monitor gonadotropin levels regularly.
In addition, if a patient did not wish to become pregnant,
they were prescribed continuous HRT. Although we rou-
tinely discontinue medication for 3 months to evaluate
whether menstruation resumes spontaneously, not all
patients agreed to intermittent HRT. Therefore, the rate
at which menstruation resumes in patients with HH is
still unclear. In addition, although we applied Kaufmann
therapy as HRT to patients with HH who did not wish
to become pregnant, different types of HRT might yield
different results. More detailed studies with large sample
sizes are necessary to evaluate this point. However, it is
plausible that menstruation may recover in patients with
hypothalamic amenorrhea who have low circulating
gonadotropin levels at their first visit.
Although fertility treatment is not initiated until
attempts have been made to treat the underlying
cause of HH, it is necessary to perform ovarian stimu-
lation for patients who wish to become pregnant.
Infertility in women with HH is caused by impaired
gonadotropin secretion from the pituitary gland due
to GnRH deficiency, which leads to a failure of follic-
ular growth and maturation. However, it should be
noted that there is no evidence for a decreased ovar-
ian reserve in patients with HH.12 Although CC is the
first-choice agent for the induction of follicular devel-
opment in patients with anovulation, especially those
with World Health Organization Group II anovula-
tory disease, it is generally believed that CC has lim-
ited efficacy in World Health Organization Group I
anovulation HH because the circulating levels of
estradiol are characteristically low in these patients.
Therefore, pulsatile GnRH or gonadotropin treatment
is recommended to induce fertility in women with
HH.7 Most patients with low gonadotropin and estra-
diol levels are reliably classified as Group I anovula-
tory disease and GnRH or gonadotropin treatment is
recommended. However, there will be some discrep-
ancies due to fluctuations in the hypothalamic–pitui-
tary–gonadal axis and the unavoidable overlap
between low and normal values of gonadotropins.
Given that hypothalamic dysfunction in Group I
patients may be variable, a revised classification that
refers to the CC-responsive or CC-resistant status has
been proposed.13 In our experience, CC is effective for
the induction of follicular development in patients
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with HH. In addition, in our basic research, using
immortalized hypothalamic kisspeptin neurons, we
have found that CC has a direct effect on kisspeptin
neurons and increases kisspeptin gene expression,
irrespective of estradiol.14 Owing to its simplicity
compared with injection, the use of CC to induce fol-
licular development in patients with HH was
established as a policy at our institution. Although
CC failed to induce follicles in one patient with pri-
mary amenorrhea, it did induce follicles in four of
eight patients with HH with secondary amenorrhea.
We did not determine the patient subset showing a
response to CC. However, based on the results for
patients with secondary amenorrhea who received
CC treatment, serum levels of LH, FSH, and E2 and
the cause of amenorrhea could not predict the respon-
siveness to CC. Pulsatile GnRH therapy is an effective
method to drive the development of single dominant
follicles; however, this therapy is not applied interna-
tionally because of the lack of a commercially avail-
able pump. In addition, the full-day attachment of a
GnRH pump is uncomfortable.
Among 16 patients with HH, nine expressed a desire
to become pregnant during follow-up, and seven of these
patients became pregnant following infertility treatment.
Two patients with HH with secondary amenorrhea
became pregnant by CC administration and timed inter-
course. The remaining five patients, including one case
with primary amenorrhea, became pregnant after gonad-
otropin administration and IVF. Thus, patients with HH
can have good reproductive outcomes after receiving
infertility treatment, as previously reported.15 For con-
trolled ovarian stimulation, we applied hMG, but not
recFSH, to all patients with HH. Women with severe
GnRH deficiency have very low gonadotropin levels. LH
stimulates ovarian theca cells to produce androgen sub-
strates, which allow for sufficient estradiol to be secreted
from maturing follicles.16 In contrast, granulosa cell stim-
ulation by FSH is an androgen-modulated process.17
Although normal follicular development in the human
ovary is predominantly dependent on FSH, LH contrib-
utes to the gonadotropin control of follicular growth.
Because women with HH are deficient in LH, the admin-
istration of HMG, but not recFSH, should be rec-
ommended for controlled ovarian stimulation. Indeed, a
previous meta-analysis demonstrated that under long-
term GnRH agonist treatment, hMG was superior to
only recFSH in IVF.18
Finally, we reported four cases whose serum
gonadotropin levels were monitored for >5 years.
Among these women, menstrual recovery was
© 2021 Japan Society of Obstetrics and Gynecology.

observed in two cases (Cases 2 and 15). Their serum
gonadotropin levels were generally low, with some
fluctuation. Menstruation restarted when gonadotro-
pin levels increased. However, serum gonadotropin
levels were occasionally elevated in Case 16; however,
spontaneous menstruation did not occur. Because this
patient received fertility treatment for a long time as
well as constant medical interventions, we missed the
chance to observe spontaneous menstruation. Surpris-
ingly, although she generally exhibited HH, her
gonadotropin serum levels increased in the meno-
pausal period. However, another decrease to
hypogonadotropic levels was subsequently observed.
It is generally agreed that hypothalamic kisspeptin
neurons are positioned at the highest level in the con-
trol of the hypothalamic–pituitary–gonadal axis. In
humans, kisspeptin neurons located in the infundibular
nucleus of the hypothalamus play a pivotal role in con-
trolling the pulsatile secretion of GnRH.19 Kisspeptin
neurons in this area are integrators of endocrine, meta-
bolic, and environmental factors.20 A variety of factors
can repress the neuronal activity of kisspeptin neurons,
leading to the suppression of GnRH release and ulti-
mately resulting in HH. Because the cause of the sup-
pression of kisspeptin neurons varies, the clinical
characteristics of HH might also differ among patients.
In this study, we retrospectively reviewed patients with
HH who exhibited amenorrhea. A number of patients
recovered spontaneous menstruation during the follow-up
period. In patients who were followed up for >5 years,
fluctuations in gonadotropin levels were observed, regard-
less of the recovery of spontaneous menstruation. CC was
effective in four of nine women with HH (44.4%) and
seven of nine women with HH became pregnant (77.8%).
Our findings show that the phenotypic spectrum of HH is
broad and patients have a good reproductive prognosis
after receiving appropriate infertility treatment.
Author Contributions
Haruhiko Kanasaki and Satoru Kyo conceived and
designed this study. Haruhiko Kanasaki, Aki Oride
and Hiroe Okada corrected clinical data. Haruhiko
Kanasaki and Hiroe Okada wrote the manuscript. All
authors read and approved the final manuscript.
Disclosure
The authors have no conflicts of interest to declare.
© 2021 Japan Society of Obstetrics and Gynecology.
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Sixteen hypogonadotropic hypogonadism cases
Data Availability Statement
The data that support the findings of this study are
available on request from the corresponding author.
The data are not publicly available due to privacy or
ethical restrictions.
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