Yarin, 3 mg+0.03 mg 21 pcs

Yarina is a low-dose monophasic combined contraceptive with anti-mineralocorticoid and anti-androgenic properties. It inhibits the secretion of gonadotropic hormones of the pituitary gland, inhibits the maturation of follicles and prevents ovulation. It increases the viscosity of cervical mucus, which makes it difficult for sperm to enter the uterus.

Drospirenone has anti-mineralocorticoid action and can prevent weight gain and other symptoms associated with fluid retention in the body.

It prevents sodium retention caused by estrogens, provides very good tolerance and has a positive effect in premenstrual syndrome. In combination with ethinylestradiol, drospirenone improves the lipid profile and increases HDL levels.

Drospirenone has antiadrogenic activity and helps to reduce the appearance of acne and reduce sebum production. It does not counteract the ethinyl estradiol-induced increase in sex hormone binding globulin (hSPH) levels, which contributes to the binding and inactivation of endogenous androgens.

Drospirenone does not have any androgenic, estrogenic, glucocorticoid or antiglucocorticoid activity, which in combination with its anti-mineralocorticoid and anti-androgenic actions gives drospirenone a biochemical and pharmacological profile very similar to natural progesterone. There is evidence for a reduced risk of endometrial and ovarian cancer.

In the background of using the drug Yarina menstrual cycle becomes more regular, painful menstruation is less often observed, the intensity of menstrual discharge decreases, as a result of which the risk of iron deficiency anemia is reduced.

Indications

Hormonal contraception.

The drug is recommended for acne and seborrhea, as well as for hormone-dependent fluid retention in the body.

Composition

1 tablet contains:

the active ingredients:

drospirenone 3 mg,

ethinylestradiol 0.03 mg;

auxiliary substances:

Lactose monohydrate, 48.17 mg;

Corn starch, 14.4 mg;

corn starch pregelatinized – 9.6 mg;

povidone K25 – 4 mg;

magnesium stearate – 800 mcg;

p> hypromellose (hydroxypropyl methylcellulose) – 1.0112 mg;

Macrogol 6000 – 202.4 µg;

Talc (magnesium disilicate) – 202.4 µg;

Titanium dioxide (E171) – 556.5 µg;

Iron (II) oxide (E172) – 27.5 µg

How to take, the dosage

To be taken by mouth, in the order given on the package, at approximately the same time each day, with a small amount of water.

Take one tablet a day continuously for 21 days. Taking pills from the next package begins after a 7-day break, during which menstrual-like bleeding (bleeding withdrawal) usually develops. It usually begins on the 2nd or 3rd day after taking the last pill and may not end until the pills from the new package start.

How to start taking Yarina®

If you have not taken any hormonal contraceptives in the previous month

Yarina® starts on the first day of your menstrual cycle (that is, the first day of menstrual bleeding). It is allowed to start taking the pills on days 2-5 of menstrual cycle, but in this case it is recommended to use an additional barrier method of contraception during the first 7 days of taking the pills from the first package.

When switching from other combined oral contraceptives, the vaginal ring, or the contraceptive patch

. It is preferable to start Yarina® the day after taking the last active pill from the previous package, but in no case later than the day after the usual 7-day break (for products containing 21 pills) or after taking the last inactive pill (for products containing 28 pills in a package).

Yarina® should be started on the day the vaginal ring or patch is removed, but no later than the day a new ring or patch is to be inserted.

When switching from gestagen-only contraceptives (“mini-pills,” injectable forms, implant) or from a gestagen-releasing intrauterine contraceptive (Mirena)

You can switch from a “mini-pill,” injectable forms, or implant. It is possible to switch from the “mini-pill” to Yarina® on any day (without a break), from the implant or intrauterine contraceptive with gestagen – on the day of its removal, from the injectable form – from the day when the next injection should be made. In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pills.

After an abortion in the first trimester of pregnancy

It is possible to start taking the drug immediately, on the day of the abortion. If this condition is met, the woman does not need additional contraception.

After delivery or after a second trimester abortion

The initiation of the drug should not begin until 21-28 days after delivery (in the absence of breastfeeding) or after a second trimester abortion. If you start taking the pills later, you should use an additional barrier method of contraception during the first 7 days of taking the pills. However, if a woman has already been sexually active, pregnancy must be excluded before taking Yarina® or the first menstrual period must be awaited.

Taking missed pills

If a woman is less than 12 hours late in taking the drug, contraceptive protection is not reduced. The woman should take the pill as soon as possible, and the next one is taken at the usual time.

If pills are missed for more than 12 hours, contraceptive protection is reduced. The more pills missed and the closer the missed pill is to a 7-day break, the greater the chance of pregnancy.

The following two basic rules can guide this:

– taking the drug should never be interrupted, for more than 7 days;

– 7 days of continuous pill taking is required to achieve adequate suppression of hypothalamic-pituitary-ovarian regulation.

Accordingly, the following advice may be given if the delay in taking the pills is more than 12 hours (the interval since the last pill is more than 36 hours).

The first week of taking the medication

The last missed pill should be taken as soon as possible, as soon as the woman remembers it (even if that requires taking two pills at the same time). The next pill is taken at the usual time. In addition, a barrier method of contraception (e.g. condom) must be used for the next 7 days. If sexual intercourse took place during the week before skipping the pill, it is necessary to consider the possibility of pregnancy.

The second week of the drug

The last missed pill should be taken as soon as possible as soon as the woman remembers it (even if this requires taking two pills at the same time). The next pill is taken at the usual time. Provided the woman has taken the pills correctly in the 7 days preceding the first missed pill, no additional contraceptive measures are necessary. Otherwise, and if two or more pills are missed, additional barrier methods of contraception (e.g., a condom) should be used for 7 days.

The third week of taking the drug

The risk of pregnancy increases because of the upcoming interruption of the pills. A woman should strictly adhere to one of the two options below. In this case, if all pills were taken correctly in the 7 days preceding the first missed pill, there is no need to use additional contraceptive methods.

1. The last missed pill should be taken as soon as possible as soon as the woman remembers it (even if this requires taking two pills at the same time). The next pills are taken at the usual time until the pills from the current package are finished. The pills from the next package should be started immediately without interruption. Bleeding cancellation is unlikely until the second package is finished, but there may be mucous discharge and breakthrough bleeding while taking the pills.

2. You can stop taking the pills from the current package, thus starting a 7-day break (including the day you missed the pills), and then start the pills from the new package.

If a woman misses taking her pills and then has no bleeding withdrawal during the break, pregnancy must be ruled out.

Recommendations in case of vomiting and diarrhea

In case of vomiting or diarrhea up to 4 h after taking the pills, absorption may not be complete, and additional precautions should be taken to prevent unwanted pregnancy. In such cases, the above recommendations for skipping the pills should be followed.

Changing the start day of menstrual bleeding

In order to delay the start of menstrual bleeding, it is necessary to continue taking the pills from the new Yarina® package without a 7-day break. The pills from the new pack can be taken as long as necessary, including until the pills from the pack are finished. During taking the drug from the second package, there may be oozing of blood from the vagina or breakthrough uterine bleeding. You should resume taking Yarina® from the next package after the usual 7-day break.

In order to reschedule menstrual bleeding to another day of the week, a woman should shorten her immediate break from taking the pills by as many days as she wants. The shorter the interval, the greater the risk that she won’t have a bleeding withdrawal, and will then experience menses and breakthrough bleeding while taking her second pack (just as she would if she wanted to delay the start of her menstrual-like bleeding).

Interaction

The interaction of oral contraceptives with other drugs may result in breakthrough bleeding and/or decreased contraceptive reliability. Women taking these drugs should temporarily use barrier methods of contraception in addition to Yarin® , or choose another method of contraception.

The following interactions have been reported in the literature.

The effect on hepatic metabolism. The use of drugs that induce hepatic microsomal enzymes may lead to increased clearance of sex hormones, which in turn may lead to breakthrough bleeding or decreased contraceptive reliability. These drugs include phenytoin, barbiturates, primidone, carbamazepine, rifampicin, rifabutin, possibly also oxcarbazepine, topiramate, felbamate, griseofulvin, and St John’s wort preparations.

HIV protease inhibitors (e.g. ritonavir) and non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine) and combinations thereof can also potentially affect hepatic metabolism.

Impact on intestinal-hepatic circulation. According to individual studies, some antibiotics (e.g., penicillins and tetracyclines) may decrease intestinal hepatic circulation of estrogen, thereby lowering the concentration of ethinyl estradiol.

When taking drugs that affect microsomal enzymes and for 28 days after their withdrawal, an additional barrier method of contraception should be used.

When taking antibiotics (such as penicillins and tetracyclines) and for 7 days after their withdrawal, an additional barrier method of contraception should be used. If during these 7 days of barrier method of contraception the pills in the current package run out, the pills from the next package of Yarina® should be started without the usual interruption of the pills.

The main metabolites of drospirenone are formed in plasma without the participation of the cytochrome P450 system. Therefore, it is unlikely that cytochrome P450 system inhibitors affect the metabolism of drospirenone.

The oral combination contraceptives may affect the metabolism of other drugs, resulting in an increase (e.g., cyclosporine) or decrease (e.g., lamotrigine) in their plasma and tissue concentrations.

Based on in vitro interaction studies as well as in vivo studies in female volunteers taking omeprazole, simvastatin and midazolam as markers, it can be concluded that the effect of drospirenone at 3 mg dose on metabolism of other drug substances is unlikely.

There is a theoretical possibility of increased serum potassium levels in women receiving Yarina® concomitantly with other drugs that may increase serum potassium levels. These drugs include angiotensin II receptor antagonists, certain anti-inflammatory drugs, potassium-saving diuretics, and aldosterone antagonists. However, in studies evaluating the interaction of drospirenone with ACE inhibitors or indomethacin, no significant difference was found between serum potassium concentrations compared with placebo.

Special Instructions

If any of the conditions, diseases, and risk factors listed below are present, the potential risks and expected benefits of combined oral contraceptives should be carefully weighed in each individual case and discussed with the woman before she decides to start taking the drug.

If any of these conditions, diseases, or increased risk factors aggravate, worsen, or first appear, the woman should consult her doctor, who may decide if the drug should be discontinued.

Cardiovascular disease

. Results of epidemiological studies suggest an association between the use of combined oral contraceptives and an increased incidence of venous and arterial thrombosis and thromboembolism (such as deep vein thrombosis, pulmonary embolism, myocardial infarction, and cerebrovascular events) when taking combined oral contraceptives. These diseases are rare.

The risk of VTE is highest in the first year of taking these drugs. An increased risk is present after initial use of combined oral contraceptives or renewed use of the same or different combined oral contraceptives (after a gap of 4 weeks or more between doses). Data from a large prospective study involving 3 groups of patients show that this increased risk is predominantly present during the first 3 months.

The overall risk of VTE in patients taking low-dose combined oral contraceptives (less than 50 mcg ethinylestradiol) is 2 to 3 times higher than in nonpregnant patients not taking combined oral contraceptives, yet this risk remains lower compared with the risk of VTE in pregnancy and childbirth. VTE can be life-threatening or fatal (in 1-2% of cases).

VTE, manifesting as deep vein thrombosis, or pulmonary embolism, can occur with any combination oral contraceptive.

Very rarely thrombosis of other blood vessels (e.g., hepatic, mesenteric, renal, cerebral veins and arteries, or retinal vessels) occurs with combined oral contraceptives. There is no consensus on the association between the occurrence of these events and the use of combined oral contraceptives.

The symptoms of deep vein thrombosis (DVT) include the following: unilateral swelling of the lower extremity or along a vein in the leg, pain or discomfort in the leg only when upright or walking, localized temperature rise in the affected leg, redness or discoloration of the skin on the leg.

The symptoms of pulmonary artery thromboembolism (TELA) are: difficulty or rapid breathing; sudden cough, including with hemoptysis; severe chest pain, which may increase with deep breaths; anxiety; severe dizziness; and rapid or irregular heartbeat.

Some of these symptoms (e.g., shortness of breath, coughing) are nonspecific, and may be misinterpreted as signs of other more or less severe events (e.g., respiratory infection).

Arterial thromboembolism can lead to stroke, vascular occlusion or myocardial infarction. Symptoms of stroke include: sudden weakness or loss of sensation in the face, arm or leg, especially on one side of the body, sudden confusion, problems with speech and understanding; sudden one- or two-sided loss of vision; sudden gait disturbance, dizziness, loss of balance or coordination of movements; sudden, severe or prolonged headache for no apparent reason; loss of consciousness or fainting with or without an epileptic seizure.

Other signs of vascular occlusion: sudden pain, swelling and mild bruising of the extremities, acute abdomen.

The symptoms of myocardial infarction include: pain, discomfort, pressure, heaviness, compression, or tumescence in the chest, arm, or behind the sternum; discomfort with irradiation to the back, cheekbone, throat, arm, stomach; cold sweat, nausea, vomiting or dizziness, severe weakness, anxiety, or shortness of breath; rapid or irregular heartbeat. Arterial thromboembolism can be fatal. The risk of thrombosis (venous and/or arterial) and thromboembolism is increased:

– with age;

– in smokers (the risk increases with more cigarettes or greater age, especially in women over 35).

If there is:

– obesity (body mass index more than 30 kg/m2);

– family history (e.g. venous or arterial thromboembolism ever in a close relative or parent at a relatively young age). If there is an inherited or acquired predisposition, the woman should be evaluated by an appropriate specialist to decide whether she should take the combined oral contraceptive;

Long-term immobilization, major surgery, any leg surgery or extensive trauma. In these situations, it is advisable to stop using combined oral contraceptives (if surgery is planned, at least 4 weeks before it) and not to resume taking them for 2 weeks after the end of immobilization;

– dyslipoproteinemia;

– arterial hypertension;

– migraine;

– heart valve disease;

– atrial fibrillation.

The possible role of varicose veins and superficial thrombophlebitis in venous thromboembolism remains controversial. An increased risk of thromboembolism in the postpartum period should be considered.

Peripheral circulatory disorders may also be seen in diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn’s disease or nonspecific ulcerative colitis) and sickle cell anemia. An increase in the frequency and severity of migraine headaches during the use of combined oral contraceptives (which may precede cerebrovascular disorders) may be grounds for immediate discontinuation of these drugs.

The biochemical indicators indicating an inherited or acquired predisposition to venous or arterial thrombosis include the following: activated protein C resistance, hyperhomocysteinemia, antithrombin-III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant). In assessing the risk-benefit ratio, it should be considered that adequate treatment of the condition in question can reduce the associated risk of thrombosis. It should also be considered that the risk of thrombosis and thromboembolism in pregnancy is higher than with low-dose oral contraceptives (ethinyl estradiol content of 0.05 mg).

Tumors

The most significant risk factor for cervical cancer is persistent papillomavirus infection. There have been reports of some increased risk of cervical cancer with long-term use of combined oral contraceptives. However, the association with taking combined oral contraceptives has not been proven. The possibility that these findings are related to disease screening is debated. There remains controversy about the extent to which these data are related to screening for cervical abnormalities or to patterns of sexual behavior (less frequent use of barrier methods of contraception).

A meta-analysis of 54 epidemiological studies found that there is a slightly increased relative risk of breast cancer diagnosed in women currently taking combined oral contraceptives (relative risk of 1.24).

The increased risk gradually disappears within 10 years of stopping these drugs. Because breast cancer is rare in women under age 40, the increase in breast cancer diagnoses in women currently or recently taking combined oral contraceptives is small relative to the overall risk of the disease.

His association with taking combined oral contraceptives has not been proven. The observed increase in risk may also be a consequence of close monitoring and earlier diagnosis of breast cancer in women who use combined oral contraceptives. Women who have ever used combined oral contraceptives are found to have earlier stages of breast cancer than women who have never used them.

In rare cases, development of benign, and in extremely rare cases, malignant liver tumors have been observed during the use of combined oral contraceptives, which sometimes led to life-threatening intra-abdominal bleeding. If severe abdominal pain, liver enlargement, or signs of intra-abdominal bleeding occur, this should be considered in the differential diagnosis. Malignant tumors can be life-threatening or fatal.

Other conditions

Clinical studies have shown no effect of drospirenone on plasma potassium concentration in patients with mild to moderate renal impairment. However, in patients with impaired renal function and baseline potassium concentration at IUF, the risk of hyperkalemia with potassium retention drugs cannot be excluded.

Women with hypertriglyceridemia (or a family history of this condition) may have an increased risk of pancreatitis when taking combined oral contraceptives.

While small increases in BP have been described in many women taking combined oral contraceptives, clinically significant increases have rarely been reported. However, if a persistent, clinically significant increase in BP develops while taking this medication, these medications should be stopped and treatment for arterial hypertension should be initiated. The drug can be continued if normal BP values are achieved with hypotensive therapy.

The following conditions have been reported to develop or worsen both during pregnancy and when taking combined oral contraceptives (but their association with taking combined oral contraceptives has not been proven): Jaundice and/or pruritus associated with cholestasis; gallstone formation; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; Sydenham’s chorea; herpes of pregnancy; and hearing loss associated with otosclerosis.

Cases of Crohn’s disease and nonspecific ulcerative colitis have also been described with combined oral contraceptives. In women with hereditary forms of angioedema, exogenous estrogens may cause or worsen symptoms of angioedema.

Acute or chronic liver dysfunction may require withdrawal of the drug until liver function parameters return to normal. Recurrent cholestatic jaundice, which develops for the first time during pregnancy or previous use of sex hormones, requires discontinuation of the drug.

While combined oral contraceptives may affect insulin resistance and glucose tolerance, there is no need to change the therapeutic regimen in diabetic patients using low-dose combined oral contraceptives (less than 0.05 mg ethinylestradiol).

Women with diabetes, however, should be closely monitored while taking this drug.

Sometimes chloasma may develop, especially in women with a history of pregnancy chloasma. Women with a history of chloasma should avoid prolonged sun exposure and exposure to UV radiation while taking Yarin®.

Preclinical safety data

Preclinical data from standard multiple-dose toxicity, genotoxicity, carcinogenic potential and reproductive toxicity studies do not indicate any particular risk to humans. However, it should be remembered that sex steroids can promote the growth of some hormone-dependent tissues and tumors.

Laboratory tests

The use of combined oral contraceptives may affect the results of some laboratory tests, including liver, kidney, thyroid, and adrenal function, plasma transport protein levels, carbohydrate metabolism, and clotting and fibrinolysis parameters. The changes usually do not go beyond the normal values. Drospirenone increases plasma renin activity and plasma aldosterone levels, which is associated with its anti-mineralocorticoid effect.

The efficacy of Yarina® may be reduced in the following cases: if the pills are missed, if vomiting and diarrhea occur (see “Missed pills”) or as a result of drug interactions.

Inadequate control of the menstrual cycle

An irregular (acyclic) bleeding/vaginal bleeding (smeary bleeding or breakthrough bleeding) may occur while taking Yarin®, especially during the first months of use.

Hence, evaluation of any irregular menstrual-like bleeding should be done after an adjustment period of approximately 3 cycles. If irregular menstrual-like bleeding recurs or develops after previous regular cycles, a thorough evaluation should be performed to rule out malignancy or pregnancy.

Some women may not develop withdrawal bleeding during a break in the pill. If Yarina® was taken as recommended, it is unlikely that the woman is pregnant. However, if irregular use of the drug and no two consecutive menstrual-like bleeding events occur, the drug cannot be continued until pregnancy is ruled out.

Medical examinations

Before starting or resuming the use of Yarin® it is necessary to review the life history, family history of the woman, conduct a thorough general medical and gynecological examination, exclude pregnancy. The scope of investigations and the frequency of check-ups should be based on the existing norms of medical practice, taking into account the individual characteristics of each patient. Typically, BP, heart rate, body mass index are measured, and the condition of the breast, abdomen, and pelvic organs is checked, including cytological examination of the cervical epithelium (Papanicolaou test). Normally, follow-up examinations should be performed at least once every 6 months.

Warn women that hormonal contraceptives do not protect against HIV infection (AIDS) and other sexually transmitted diseases.

The effect on the ability to drive a car or perform work requiring increased speed of physical and mental reactions. Not detected.

Contraindications

– presence of thrombosis (venous and arterial) currently or in the anamnesis (for example, deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders);
– History or presence of the conditions preceding the thrombosis (for example, transient cerebrovascular disorders, angina pectoris);
– Diabetes mellitus with vascular complications;
– Severe or multiple risk factors for venous or arterial thrombosis;
– current or past history of severe liver disease (until liver function test values normalize);
– current or past history of benign or malignant liver tumors;
– identified or suspected hormone-dependent malignant diseases of genitalia or mammary glands;
– severe or acute renal insufficiency;
– vaginal bleeding of unknown genesis;
– pregnancy or suspected pregnancy;
– lactation (breast-feeding);
– hypersensitivity to the preparation components.

Side effects

The most commonly reported adverse reactions to Yarina® include nausea and breast pain. They occurred in more than 6% of women using the drug.

Serious adverse reactions are arterial and venous thromboembolism.

The table below shows the frequency of adverse reactions reported in clinical trials of Yarin® (N=4897). Within each group, separated according to the frequency of adverse reactions, the adverse reactions are presented in decreasing order of severity. They are divided by frequency into frequent (≥1/100 and

Table 1

Table 1 System-organ classes (MedDRA version)FrequentFrequentFrequent UnknownPsychiatric disordersMood swings, depression, depressed mood, decreased or lost libidoNervous systemMigraine Vascular disordersVenous or arterial thromboembolism* GI tractNausea Skin and subcutaneous tissue erythema multiformeProductive system and breast painMammary gland pain, Irregular uterine bleeding, unspecified genital bleedingMammary gland hypertrophyVaginal discharge, discharge from mammary glands/p>

The adverse events in the clinical trials were codified using the MedDRA dictionary (Medical Regulatory Activity Dictionary, version 12.1). Different MedDRA terms reflecting the same symptom were grouped together and presented as a single adverse reaction to avoid diluting or blurring the true effect.

* – Approximate frequency from epidemiological studies covering a group of combined oral contraceptives. The frequency bordered on the very rare.

– Venous or arterial thromboembolism includes the following nosological units: peripheral deep vein occlusion, thrombosis and embolism/pulmonary occlusion, thrombosis, embolism and infarction/myocardial/ cerebral infarction and stroke not defined as hemorrhagic.

For venous and arterial thromboembolism, migraine see also Contraindications and Special Indications.

Further Information

The following are adverse reactions with very rare occurrence or delayed symptoms that are thought to be related to taking combined oral contraceptives (see also Contraindications and Special Precautions).

Tumors:

The incidence of breast cancer in women taking combined oral contraceptives is slightly higher. Because breast cancer is rare in women under age 40, the increase in breast cancer diagnoses in women taking combined oral contraceptives is small relative to the overall risk of the disease.

Liver tumors (benign and malignant).

Other conditions:

– erythema nodosa;

– women with hypertriglyceridemia (increased risk of pancreatitis while taking combined oral contraceptives);

– increased BP;

– conditions that develop or worsen while taking combined oral contraceptives, but their association with taking the drug has not been proven (jaundice and/or pruritus associated with cholestasis; gallstone formation; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome Sydenham’s chorea; pregnancy herpes; otosclerosis-related hearing loss);

– in women with hereditary angioedema, taking estrogen may cause or exacerbate its symptoms;

– liver function disorders;

– impaired glucose tolerance or effect on insulin resistance;

– Crohn’s disease, ulcerative colitis;

– chloasma;

– hypersensitivity (including symptoms such as rash, urticaria).

Overdose

Symptoms (based on cumulative experience with oral contraceptives): nausea, vomiting, oozing or metrorrhagia.

Treatment: symptomatic. There is no specific antidote.

Serious disorders in overdose have not been reported.

Pregnancy use

The drug is not prescribed during pregnancy and while breast-feeding. If pregnancy is detected while taking Yarina® , it should be stopped immediately.

However, extensive epidemiological studies have not found an increased risk of developmental defects in children born to women who received sex hormones before pregnancy or teratogenic effects in cases of reckless administration of sex hormones in early pregnancy.

At the same time, data on the results of taking Yarin® during pregnancy are limited, which does not allow any conclusions about the negative effects of the drug on pregnancy, the health of the newborn and the fetus. No significant epidemiological data are available at this time.

The use of combined oral contraceptives may decrease the amount of breast milk and change its composition, so their use is not recommended until cessation of breastfeeding. A small amount of sex steroids and/or their metabolites may be excreted with milk.