In women:
- Anovulation (including polycystic ovary syndrome);
- Controlled ovarian hyperstimulation for the purpose of inducting the development of multiple
follicles in connnection with assisted reproduction medicine [e.g.: in‑vitro fertilisation/ embryo
transfer (IVF/ET) and intracytoplasmatic sperm injection (ICSI)].

In men:
- Insufficient spermatogenesis caused by hypogonadotropic hypogonadism.

Treatment with Menogon® should be initiated under the supervision of a physician experienced in the
treatment of fertility problems. The duration of use depends on the corresponding indication.
Posology
The dosage regimens described in the following apply to both subcutaneous and intramuscular
administration.
Women:
Inter- and intra individually, the ovaries react in very different ways to administered gonadotropins.
Therefore, producing a universally applicable dosage scheme is not possible. The dosage should
thus be adapted individually to the ovaries’ response. Menogon® can be administered alone or in
combination with a gonadotropin-releasing hormone (GnRH) agonist or antagonist. Recommendations
on the dosage and duration of treatment depend on the corresponding treatment protocol.
Women with anovulation:
The Menogon® therapy should be commenced within the first 7 days of the menstruation cycle. For
at least 7 days of treatment, a daily dosage of 75 to 150 IU of Menogon® is recommended. The dosage
should not be increased after less than 7 days, the recommended dose increment is 37.5 IU and the
increase should not exceed 75 IU per step. The maximum daily dosage should not exceed 225 IU. In case
there is no optimal reaction achieved after 4 weeks of treatment, the treatment should be interrupted
for this cycle and started again with a higher dosage in a new cycle.
Once an optimal reaction has been achieved, one single injection of 5,000 to 10,000 IU hCG should be
administered one day after the last Menogon® injection.
The patient should have sexual intercourse both on the day of hCG administration and on the following
day. Alternatively, an intrauterine insemination can be performed. The patients should be closely
followed up for at least 2 weeks following the hCG administration. If an excessive reaction to Menogon®
is observed, the course of treatment should be stopped, and no hCG should be administered. The
patient should use non-hormonal contraceptives or renounce sexual intercourse until the beginning of
the next menstrual bleeding.
Women with controlled ovarian hyperstimulation for development of multiple follicles for assisted
reproduction technology (ART):
In a protocol using down-regulation with a GnRH agonist, the Menogon® therapy should be
commenced about 2 weeks after the beginning of the agonist treatment.
In a protocol using down-regulation with a GnRH antagonist, Menogon® therapy should start on day
2 or 3 of the menstrual cycle.
For at least the first 5 days of treatment, a daily dosage of 150 to 225 IU of Menogon® is recommended.
In accordance with clinical control (including ultrasound, preferably in combination with measurement
of estradiol values), the subsequent treatment of the patient should be individually adapted; the
increase of dosage should not exceed 150 IU per step. The maximum daily dosage should not exceed
450 IU. In general, the treatment should not exceed 20 days.
Once an optimal reaction has been achieved, one single injection of up to 10,000 IU hCG should be
administered to finish the follicular maturation to prepare the oocytes’ release. The patients should
be closely followed up for at least 2 weeks following the administration of hCG. If an excessive
reaction to Menogon® is observed, the course of treatment should be stopped, and no hCG should be
administered. The patient should use non-hormonal contraceptives or renounce sexual intercourse
until the beginning of the next menstrual bleeding.
Men:
After normalization of the testosterone level following administration of the appropriate dosage of hCG
(e.g. 1,500 to 5,000 IU, 3 times a week) for 4 to 6 months, Menogon® can be administered three times a
week with a dosage of 75 or 150 IU, in combination with hCG with the recommended dosage of 1,500 IU
three times a week. The combined treatment should be continued for at least three to four months until
an improvement of spermatogenesis can be seen. In case the patient does not respond after this period,
combination therapy might be necessary until spermatogenesis is achieved. Current clinical data show
that 18 months of treatment (or even more) can be necessary until spermatogenesis is achieved.
Method of administration: Menogon® is intended for subcutaneous (S.C) or intramuscular (I.M) injection
after reconstitution with the solvent provided. Shaking should be avoided. The solution should not be
used if it contains particles or if it is not clear.

- Hypersensitivity to Menotrophin or to any of the excipients. In women: - Pregnancy; - Ovarian enlargement or cysts that are not caused by a polycystic ovary syndrome; - Vaginal bleeding of unknown cause; - Uterus, ovarian and breast tumors. In men: - Testicular tumors; - Prostate carcinoma. In case of dysfunctions of the thyroid gland and the adrenal cortex, in case of hyperprolactinemia and with tumors in the hypophysis or the hypothalamus corresponding treatment has to be performed prior to the beginning of the therapy with HMG. Menogon® may not be used if non-achievement of the therapy aims is predictable. This applies to women with: - Primary ovarian insufficiency; - Deformation of the sexual organs that make pregnancy impossible; - Uterine myomas that make pregnancy impossible. This applies to men with: - Primary testicular insufficiency.

Menogon® is a potent gonadotropic substance that can have mild up to severe side effects. It should
only be administered under supervision of medical doctors who are familiar with the problems and
treatment of fertility disorders.
Therapies with gonadotropins require a certain expenditure of time from doctors and medical staff
as well as appropriate monitoring facilities. A secure and effective use of Menogon® requires regular
control of the ovarian reaction by use of ultrasound, preferably in combination with measurement of
serum estradiol levels. Inter individually, the reaction to the FSH administration can vary and can be very
low in some patients. In order to achieve therapy aims, the lowest effective dosage in relation to the
aims of treatment should be administered.
The first Menogon® injection should be performed under direct medical supervision.
Women:
Prior to the treatment, the couple’s infertility is to be diagnosed in an appropriate way and possible
contraindications for pregnancy are to be assessed. The patients are to be examined for hypothyreosis,
insufficiency of the adrenal cortex, hyperprolactinemia, and hypophysis or hypothalamus tumors and
should be treated accordingly.
In patients who undergo stimulation of the follicular growth – in connection with treatment of
anovulatory infertility or ART – enlargement of the ovaries or hyperstimulation may occur. These
risks can be minimized by adherence to the recommended dosage and administration regimens and
through thorough monitoring of the therapy.
The assessment of the follicular development is to be performed by a medical doctor who is
experienced in this context.
Ovarian Hyperstimulation Syndrome (OHSS): OHSS differs from uncomplicated ovarian enlargement
and can manifest with increasing grades of severity. It includes marked enlargement of the ovaries, high
levels of sexual hormones and increase of the fluid permeability of the vessels. The latter can lead to
fluid accumulation in the peritoneal, pleural and, in rare cases, in the pericardial cavities.
The following symptoms can be observed in severe cases of OHSS: abdominal pain, distended
abdomen, excessive ovarian enlargement, increase in weight, dyspnea, oliguria, and gastrointestinal
symptoms such as nausea, emesis and diarrhea. The clinical examination may reveal hypovolemia,
hemoconcentration, electrolyte balance disorders, ascites, hemoperitoneum, pleural effusion,
hydrothorax, acute shortness of breath, and thromboembolism. Excessive ovarian reaction to
the gonadotropin treatment rarely leads to OHSS unless the ovulation is not triggered by hCG
administration. It is thus advisable not to administer hCG with ovarian hyperstimulation and to instruct
the patient to renounce sexual intercourse or use non-hormonal contraceptives for at least 4 days. OHSS
can progress very quickly (between 24 hours and several days) and develop to serious symptoms.
Therefore, patients should be controlled for a period of at least 2 weeks following the hCG
administration. Adherence to the recommended dosage and administration regimens and thorough
monitoring of the therapy can minimize the appearance of ovarian hyperstimulation and multiple
pregnancy. With ART, aspiration of all follicles prior to ovulation can reduce the risk of hyperstimulation.
OHSS can be more severe and of longer duration in cases of pregnancy. OHSS appears most frequently
after completion of hormonal treatment and reaches its peak about 7 to 10 days after treatment.
Normally, OHSS recedes spontaneously with the beginning of menstruation. In cases of severe OHSS,

the gonadotropin treatment should be stopped (if this has not been done yet), the patient is to be
admitted to hospital, and a special OHSS treatment is to be started.
OHSS appears more frequently in women with polycystic ovarian syndrome (PCOS).
Multiple Pregnancy: Multiple pregnancy, particularly those of higher order, bear an increased risk of
maternal and perinatal complications. In patients who undergo an ovulation induction with Menogon®,
the risk of multiple pregnancy is higher in relation to natural conception. In order to minimize the risk
of multiple pregnancy, thorough monitoring of the ovarian reaction is recommended. In patients who
undergo ART, the risk of multiple pregnancy mainly depends on the number of transferred embryos,
their quality and the patient’s age. Prior to the treatment, the patient is to be informed about the
potential risk of multiple pregnancy.
Premature Birth/ Miscarriage: Premature birth or miscarriage are seen more frequently in patients
who undergo ART or a stimulation of follicular growth for the purpose of causing ovulation than in the
average population.
Ectopic pregnancy: In women with a history of tubal diseases, there is a risk of ectopic pregnancy, no
matter if pregnancy has been caused by spontaneous conception or by fertility treatment. A prevalence
of 2 to 5% of ectopic pregnancy after IVF has been reported, in relation to 1 to 1.5% in the normal
population.
Neoplasms of the Reproduction Organs: In women who have undergone multiple fertilization
treatment cycles, benign and malign neoplasms of the ovaries and other reproduction organs have
been reported. It is still in question as to whether treatment with gonadotropins increases the basic risk
of these tumors in infertile women.
Congenital Deformations: The prevalence of congenital deformations following ART can be slightly
higher than with spontaneous conception. This can probably be attributed to different parental prior
encumbrance (e.g. mother’s age, sperm characteristics) and multiple pregnancy.
Thromboembolism: Women with generally recognized risk factors for thromboembolic events, such
as personal or family history, severe obesity (Body Mass Index > 30 kg/m2) or thrombophilia may have
an increased risk of venous or arterial thromboembolic events, during or following treatment with
gonadotropins. In these women, the benefits of gonadotropin administration need to be weighed
against the risks. It should be noted however, that pregnancy itself also carries an increased risk of
thromboembolic events.
Men:
Increased endogenous FSH levels indicate a primary testicular disorder. These patients do not respond
to Menogon®/ hCG therapy. Sperm analyses are to be performed 4 – 6 months after the beginning of
treatment to enable assessment of the reaction to the therapy.
The use of Menogon® may lead to positive results in doping tests. The use of Menogon® for doping
purposes may endanger health.
Menogon® contains sodium, but less than 1 mmol (23 mg) sodium per dose, i.e. essentially
“sodium‑free”.

No interaction studies have been performed with Menogon® in human beings. Although there is no
clinical experience it is to be expected that the simultaneous use of Menogon® and Clomifen citrate
can increase the follicular response. With use of a GnRH agonist for the purpose of hypophyseal
desensitisation, a higher dose of Menogon® may be required to achieve a sufficient follicular reaction.

Fertility: Menogon® is indicated for use in infertility.
Pregnancy: Menogon® is contraindicated in women who are pregnant.
Lactation: Menogon® is contraindicated in women who are lactating.

No studies on the effects on the ability to drive and use machines have been performed. However,
Menogon® is unlikely to have influence on the patients’ ability to drive and use machines.

Very Common (≥1/10): Reactions* and pain at the site of injection.
Common (≥1/100 to <1/10): Nausea, abdominal pain, emesis, flu‑like symptoms, headache, mild,
moderate and severe OHSS, rash.
Uncommon (≥1/1,000 to <1/100): Fever.
Very Rare (<1/10,000): Hypersensitivity.
*Reactions at the site of injection have been observed in 55‑60% of the participants in clinical studies
on local tolerability. In about 12%, the reaction has been assessed as severe. In most cases, the reaction
occurred following subcutaneous administration. After intramuscular administration, reactions at the
site of injection have been observed in up to 13% of the study participants.
Menogon® treatment has shown single cases of anaphylactic reactions.
In connection with ovarian hyperstimulation, the use of gonadotropins has shown single cases of
thromboembolic complications and ovarian torsions.
Pregnancy commencing subsequent to infertility treatment with gonadotropins such as Menogon® can
end up in spontaneous abortion more frequently than normal pregnancy.
Men:
In connection with treatment with gonadotropins, gynecomastia, acne and increase in weight have
been reported.

Treatment with HMG can lead to a hyperstimulation of the ovaries which, however, in most cases
becomes clinically relevant only after the administration of hCG for the purpose of triggering ovulation.
With mild hyperstimulation (grade I) with mild ovarian enlargement (ovarian size 5 - 7 cm), with excessive
steroid secretion and abdominal problems, no therapy is required. However, the patient is to be
informed and thoroughly followed up. With hyperstimulation (grade II) with ovarian cysts (ovarian size
8 - 10 cm), abdominal symptoms, nausea and emesis, clinical monitoring and symptomatic treatment or,
if necessary, intravenous volume substitution with higher hemoconcentration is indicated.
With severe hyperstimulation (grade III) with large ovarian cysts (ovarian size > 10 cm), ascites,
hydrothorax, distended abdomen, abdominal pain, dyspnea, salt retention, hemoconcentration,
increased blood viscosity and increased platelet aggregation with the danger of thromboembolism,
admission to hospital is inevitable, since life-threatening conditions could arise, making intensive
medical measures necessary.

Pharmacotherapeutic group: Gonadotropins.
ATC code: G03GA02.
The target organs of the hormonal effect of HMG are the ovaries and testes. HMG has a gametotrophic
and steroidogenic effect. By use of the FSH component, HMG induces an increase of the growing
follicles in the ovaries and stimulates their development. FSH increases the production of estradiol
in the granulosa cells by aromatizing androgens that emerge from the theca cells under influence of
the LH component. In the testicles, FSH induces the transformation from immature to mature Sertoli
cells. It mainly has an effect on the maturation of the sperm channels and the development of the
spermatozoa. However, a high intra testicular androgen concentration is necessary, which requires
previous treatment with HCG.

HMG is orally ineffective and requires intramuscular or subcutaneous injection. The pharmacokinetics
of HMG following intramuscular and subcutaneous application has been examined specifically for each
preparation. The maximum serum level of FSH is reached 6 – 48 hours after intramuscular injection
and 6 – 36 hours after subcutaneous injection. Subsequently, the serum level decreases with a 56‑hour
(intramuscular) resp. 51‑hour (subcutaneous) half‑life. HMG is mainly excreted renally.
Bioavailability
The bioavailability of Menogon® is higher after subcutaneous application than after intramuscular
application. The FSH values after intramuscular and subcutaneous application (dosage: 300 IU) were:
• Intramuscular: AUC0 - = 320.1 mlE/ml x h; Cmax = 4.15 mlE/ml; Tmax = 18 h
• Subcutaneous: AUC0 - = 385.2 mlE/ml x h; Cmax = 5.62 mlE/ml; Tmax = 12 h

N/A

Powder: lactose monohydrate, sodium hydroxide.
Solvent: Sodium chloride, hydrochloric acid 10%, water for injection.

Not applicable.

See outer carton.

Do not store above 25°C. Do not freeze. Store in the original
container in order to protect form light.

5 ampoules of powder and 5 ampoules of solvent or 10 ampoules of powder and 10 ampoules of solvent.
Not all pack sizes may be marketed.

N/A