**11. Contraceptive pills**

It is a complex issue that causes family embarrassment to healthcare professionals in government officials in civil servants and young people themselves. There has been extensive effort to increase the use of contraceptive methods and in particular the condom to avoid pregnancies and sexual transmitted diseases.

Definitely it is necessary to set up Family Planning Centers for Teenagers, which must become a priority for each government. Basic award principle for contraceptive pills, as long as necessary, as little as possible [50]. Contraceptive capacity of contraceptive pills is estimated by the Pearl Index (Pearl Index). All formulations with combined oral hormonal contraception have Pearl index ≤1.25 women (years). There are several differences regarding the hormonal components contained in each formulation which may vary depending on the type, composition, quantity, and number of active tablets. Single-phase formulations contain active tablets with the same constant amount of estrogen and progestogen ratio. In contrast, the above ratio changed in the multiphase pills. Biphasic have two different combinations, the three phase and recently there are also four phases with successive decrease in the estrogen ratio and corresponding increase in the progestogen ratio. Contraceptive pills have not been associated with weight gain and mood changes. It is recommended to take single-phase pills in teenagers for their menstrual bleeding disorders [51–55].

Contraindications of contraceptive pills are BP ≥160/100 mmHg, liver disease, migraines with focal neurological symptoms, diabetes, nephropathy, neuropathy, retinopathy, or angiopathy complications are also included.

History of thromboembolism (particularly with third generation pills with drospirenone), thrombophilia, factor V Leiden mutation, factor II mutation (G20210A allele), antiphospholipid antibodies, protein C deficiency, protein S deficiency, antithrombin III deficiency, undiagnosed vaginal bleeding, and estrogen-dependent breast cancer compromise contraindications for contraceptive pills. Smoking is a relative contraindication for the use. According to FDA (April 2012), revision of contraceptive pills guidelines with drospirenone increases three times the risk of thrombosis compared to other progestogens. Clots are caused by contained estrogen.

#### **11.1. Impact of thrombophilia**


#### **11.2. Positive actions**

Circulation disorders such as hypermenorrhea, hypomenorrhea, metrorrhagia restoring a normal menstrual cycle, and prolong the menstrual cycle. Dysmenorrhea decreases through the action of prostaglandin synthesis. They also improve the presence of premenstrual syndrome, premenstrual edema, irritability, anxiety, and depression.

Contraceptive pills advantages include ovarian cysts treatment, endometriosis, dysmenorrhea, dyspareunia, metrorrhagia, acne and decreased androgen synthesis, hirsutismus, specific activity of estrogen and antiandrogens, mastodynia, symptom reduction mastopathy,

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What do women think about birth control pills from our own child and adolescent gynecology center housed in the Democritus University Family Planning Laboratory. Positive effects: positive effect on sexual life, reliability, easy to use/comfort, less bleeding, regulation of men-

Negative effects: nausea, headaches, changes in mood, feeling of tension on the breasts, and

Oral contraceptive pills (OCPs) perform their action through a variety of mechanisms, through the inhibition of the mesocyclic peak of gonadotropin secretion resulting in the suppression

Contraceptive action is mainly exercised through the progesterone of OCPs, which cause ovu-

• ↓ of fertilization capacity of the semen, the disturbance of normal motility and occlusion of

Estrogens exert their contraceptive action, but they are dose-dependent, by inhibiting the secretion of gonadotropins (FSH and LH), cause the uterus to change its secretory capacity of

There are several differences regarding the hormonal components contained in each formulation which may vary depending on the type, composition, quantity, and number of active tablets. Single-phase formulations contain active tablets with the same constant amount and estrogen and progestogen ratios. In contrast to multiphase, the above ratio changes of biphasic have two different combinations, the three phase have three and recently, there are also four phases with successive reductions in the estrogen ratio and a corresponding increase in

• The thickening of the cervical mucus and ↓ of the sperm penetration.

• Obstruction of implantation due to endometrial perforation [62, 63].

reduction of benign mastopathy, and bone increase density [60, 61].

struation, and less painful periods.

• Suspension of implantation

• Thickening of cervical mucus

• ↓ Luteinizing hormone (LH).

the fallopian tubes.

• Sperm motility disorder [62, 63].

lation suppression by multiple mechanisms:

the cellular structure of the endometrium.

the progesterone ratio [62, 63].

• Ovulation inhibition

of ovulation.

**11.3. Action mechanism of contraceptive pills**

increase of weight.

Ovary cancer risk is decreased by about 20% per 5 years of use and 50% for 15 years.

There is no protective action for mucosal ovarian cancer. They decrease the risk of endometrium cancer by 50% every 4 years of use and 70% after 12 years. Cancer of cervix represents an independent factor with a relative risk probably due to co-factors (HPV, intercourse without condoms). According to the WHO, there is a slight increase in the relative risk for users of contraceptive pills over a period of >4 years. Higher relative risk is increased for users over 10 years. The above may be affected by the use of non-barrier methods by the number of sex partners by multiparity and alcohol consumption.

It is believed that hormonal contraception, especially estrogen as mitotic agents, enhances neoplastic process particularly in women with HPV infection. Estrogenic probably affects specific DNA sequences.

Additionally, there is a direct interaction between estrogen receptors and HPV E6 and E7 protein. The problem of the possible relationship between breast cancer and hormone therapy is still largely unresolved.

The results that are available now suggest that relatively short-term treatment (less than 5 years) does not increase the risk.

For a treatment with longer duration, the existing results based primarily on estrogen monotherapy do not allow clear conclusions without excluding the possibility that the frequency could increase under these conditions. It is difficult to evaluate the role of progestogen added to the above treatment. So, it is preferable to utilize steroid hormones with anti-mitotic activity. It is known that hydroxyprogesterone derivatives such as medroxyprogesterone acetate can inhibit tumor growth activities.

There are indications that use of contraceptive pills over a period of 10 years can cause a moderate increase of the relative risk (24%) to the oncogenic progression for breast cancer. With discontinuation, this risk decreases to 0% in 10 years. It is also gained ground the aspect that this risk is greater in women with a family history, with the risk of being limited to second degree relatives. It is unlikely, however, to incriminate only estrogen because of the fact that there are minimal estrogen receptors in normal breast epithelial cells.

The progesterone may promote the mitotic process and cause atypia. It is known that the mitotic action on MCF-7 cells of human breast cancer of 19 nor-progestogen (norethindrone, gestodene, and 3-ketodesogestrel) [56–60].

In conclusion, progestogen should be emphasized that any attempt to adapt to the clinical practice of the experimental anti-mitotic action of a pregestogen should be done very carefully. Only well-tested prospective clinical trials may answer the question whether the protective effect found in the laboratory has the potential clinical application.

Contraceptive pills advantages include ovarian cysts treatment, endometriosis, dysmenorrhea, dyspareunia, metrorrhagia, acne and decreased androgen synthesis, hirsutismus, specific activity of estrogen and antiandrogens, mastodynia, symptom reduction mastopathy, reduction of benign mastopathy, and bone increase density [60, 61].

What do women think about birth control pills from our own child and adolescent gynecology center housed in the Democritus University Family Planning Laboratory. Positive effects: positive effect on sexual life, reliability, easy to use/comfort, less bleeding, regulation of menstruation, and less painful periods.

Negative effects: nausea, headaches, changes in mood, feeling of tension on the breasts, and increase of weight.

#### **11.3. Action mechanism of contraceptive pills**


**11.2. Positive actions**

198 Family Planning

DNA sequences.

is still largely unresolved.

5 years) does not increase the risk.

can inhibit tumor growth activities.

gestodene, and 3-ketodesogestrel) [56–60].

Circulation disorders such as hypermenorrhea, hypomenorrhea, metrorrhagia restoring a normal menstrual cycle, and prolong the menstrual cycle. Dysmenorrhea decreases through the action of prostaglandin synthesis. They also improve the presence of premenstrual syn-

There is no protective action for mucosal ovarian cancer. They decrease the risk of endometrium cancer by 50% every 4 years of use and 70% after 12 years. Cancer of cervix represents an independent factor with a relative risk probably due to co-factors (HPV, intercourse without condoms). According to the WHO, there is a slight increase in the relative risk for users of contraceptive pills over a period of >4 years. Higher relative risk is increased for users over 10 years. The above may be affected by the use of non-barrier methods by the number of sex

It is believed that hormonal contraception, especially estrogen as mitotic agents, enhances neoplastic process particularly in women with HPV infection. Estrogenic probably affects specific

Additionally, there is a direct interaction between estrogen receptors and HPV E6 and E7 protein. The problem of the possible relationship between breast cancer and hormone therapy

The results that are available now suggest that relatively short-term treatment (less than

For a treatment with longer duration, the existing results based primarily on estrogen monotherapy do not allow clear conclusions without excluding the possibility that the frequency could increase under these conditions. It is difficult to evaluate the role of progestogen added to the above treatment. So, it is preferable to utilize steroid hormones with anti-mitotic activity. It is known that hydroxyprogesterone derivatives such as medroxyprogesterone acetate

There are indications that use of contraceptive pills over a period of 10 years can cause a moderate increase of the relative risk (24%) to the oncogenic progression for breast cancer. With discontinuation, this risk decreases to 0% in 10 years. It is also gained ground the aspect that this risk is greater in women with a family history, with the risk of being limited to second degree relatives. It is unlikely, however, to incriminate only estrogen because of the fact that

The progesterone may promote the mitotic process and cause atypia. It is known that the mitotic action on MCF-7 cells of human breast cancer of 19 nor-progestogen (norethindrone,

In conclusion, progestogen should be emphasized that any attempt to adapt to the clinical practice of the experimental anti-mitotic action of a pregestogen should be done very carefully. Only well-tested prospective clinical trials may answer the question whether the protec-

there are minimal estrogen receptors in normal breast epithelial cells.

tive effect found in the laboratory has the potential clinical application.

Ovary cancer risk is decreased by about 20% per 5 years of use and 50% for 15 years.

drome, premenstrual edema, irritability, anxiety, and depression.

partners by multiparity and alcohol consumption.


Oral contraceptive pills (OCPs) perform their action through a variety of mechanisms, through the inhibition of the mesocyclic peak of gonadotropin secretion resulting in the suppression of ovulation.

Contraceptive action is mainly exercised through the progesterone of OCPs, which cause ovulation suppression by multiple mechanisms:


Estrogens exert their contraceptive action, but they are dose-dependent, by inhibiting the secretion of gonadotropins (FSH and LH), cause the uterus to change its secretory capacity of the cellular structure of the endometrium.

There are several differences regarding the hormonal components contained in each formulation which may vary depending on the type, composition, quantity, and number of active tablets. Single-phase formulations contain active tablets with the same constant amount and estrogen and progestogen ratios. In contrast to multiphase, the above ratio changes of biphasic have two different combinations, the three phase have three and recently, there are also four phases with successive reductions in the estrogen ratio and a corresponding increase in the progesterone ratio [62, 63].

With regard to the first few generations because the dosage did not decrease at the appropriate time, side effects such as unwanted bleeding or spotting often occurred. The second generation was more effective and longer half-life, but with increased androgenic action that helped to sexual desire, however, it could lead to hypertrichosis, acne, and dyslipidemia. The third generation retains the effectiveness of the progestogen while reducing its androgenic effect. Smaller androgenic effect also makes estrogen more effective. This however entails a greater risk for thromboembolic events [62, 63].

**11.7. Implants**

often [65].

strual disorders [65].

**11.10. Subdermal implants**

**11.11. Injectable progestogens**

menstrual disorders [67].

*11.11.1. Barrier methods*

• Male condoms.

• Female condoms.

valerian estradiol, and norethrone acetate.

**11.8. Injectable contraceptive preparations**

protection 3 months with efficacy 99.7%.

depot, valerian estradiol, and norethrone acetate.

**11.9. Transdermal contraceptive patches evra**

They modify cervical mucus (viscosity in reduced amount) prevent sperm penetration and

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It is an ideal contraceptive method for teenagers who do not want to deal with contraception

Injectable contraceptive preparations medroxyprogesterone acetate depot, intramuscular

Monthly combined contraceptives estradiol cypionate and medroxy progesterone acetate

They improve dysmenorrhea increase the risk of thromboembolic events and may cause men-

Transdermal contraceptive patches evra release ethinyl estradiol 600 μg with norelgestromin 6 mg. They remain placed for 7 days for 3 consecutive weeks followed by 1 week without patch it is a useful alternative for women who hardly remember daily taking the tablet because if they forget there is a 2 day error margin. They should be avoided when weight of the woman is greater than 90 kg. There is an increased exposure to estrogen compared to oral contraceptive pills 1.6 and 1.2–2.2 with higher probability of deep vein thrombosis [65, 66].

They modify cervical mucus (viscosity in a reduced amount), prevent sperm penetration, and suppress endometrial growth which becomes inappropriate for implantation. It is an ideal contraceptive method for teenagers who do not want to deal with contraception often [65].

Injectable progestogens contain depot medroxyprogesterone acetate, intramuscular site of

Combined oral contraceptive pills estradiol cypionate and depot medroxyprogesterone acetate,

They improve dysmenorrhea, increase the risk of thromboembolic events, and may cause

injection and they offer protection for 3 months with efficacy 99.7%.

suppress endometrial growth which becomes inappropriate for implantation.

#### **11.4. 4th generation contraceptive pills**

The widespread use of a combination of estrogen and progesterone as a contraceptive or hormone replacement therapy has made it possible to complete large epidemiological studies that have made it possible to assess the benefits and risks that may have arisen.

Among the major advantages of use, are included primarily the reduced incidence of endometrium cancer, attributed mainly to the antimitotic progesterone activity, and secondly, the reduced frequency of ovaries cancer, due anti-gonadotropic action combination [62, 63].

#### **11.5. Contraceptive vaginal ring**

It releases daily and for 21 days 120 μg of etonogestrel and 15 μg of ethinylestradiol (nestorone ring study 15–20 μg EU + 150–200 μg nestorone).

It remains in place for 3 weeks and the fourth week it is removed for bleeding to escape. It is possible to be removed during sexual intercourse.

Existing progesterone: etonogestrel (3-keto desogestrel) 19-nortestosterone derivative.

Nestorone belongs to the norprogesterone family and is weakly active by oral administration. It does not bind significantly neither to the androgen receptor, nor to the estrogen receptor. It is a flexible, transparent silicone ring. It secrets daily 15 μg ethinylestradiol and 120 μg etonogestrel. Its diameter is 53 mm with cross section 4 mm. The duration of usage is 1 month, 3 weeks/1 week.

It is direct start fitting and has possibility to maintain up to 35 days. The next placement can be without delay. There is less interruption for a shorter duration of menstruation. Tampons, spermicide nonoxynol-9, or intravaginal miconazole should not to be used at the same time. It can be removed in less than 3 hours. It does not affect in sexual contact.

It causes breast tenderness, headaches and nausea, spotting, vaginal intolerance or hypersecretion, and unconceivable loss or misuse. There are no studies evaluating its effect on adolescent bones. There is no evidence of VTE in relation to low-dose OCPs. Ease of use has not demonstrated increased compliance or prolonged use (<30% in 6 months) [64, 65].

#### **11.6. Evra patch contraceptives**

They release EE 600 μg with norelgestromin 6 mg. They remain placed for 7 days for 3 consecutive weeks followed by 1 week without patch. It is a useful alternative method for women who hardly remember daily taking the pill because if they forget there is a 2 day error margin. It should be avoided when weight greater than 90 kg. The increased exposure to estrogen compared to oral contraceptive pills creates 1.6 and 1.2–2.2 higher probability of deep thrombosis [65, 66].

#### **11.7. Implants**

With regard to the first few generations because the dosage did not decrease at the appropriate time, side effects such as unwanted bleeding or spotting often occurred. The second generation was more effective and longer half-life, but with increased androgenic action that helped to sexual desire, however, it could lead to hypertrichosis, acne, and dyslipidemia. The third generation retains the effectiveness of the progestogen while reducing its androgenic effect. Smaller androgenic effect also makes estrogen more effective. This however entails a

The widespread use of a combination of estrogen and progesterone as a contraceptive or hormone replacement therapy has made it possible to complete large epidemiological studies

Among the major advantages of use, are included primarily the reduced incidence of endometrium cancer, attributed mainly to the antimitotic progesterone activity, and secondly, the reduced frequency of ovaries cancer, due anti-gonadotropic action combination [62, 63].

It releases daily and for 21 days 120 μg of etonogestrel and 15 μg of ethinylestradiol (nesto-

It remains in place for 3 weeks and the fourth week it is removed for bleeding to escape. It is

Nestorone belongs to the norprogesterone family and is weakly active by oral administration. It does not bind significantly neither to the androgen receptor, nor to the estrogen receptor. It is a flexible, transparent silicone ring. It secrets daily 15 μg ethinylestradiol and 120 μg etonogestrel. Its diameter is 53 mm with cross section 4 mm. The duration of usage is 1 month, 3 weeks/1 week. It is direct start fitting and has possibility to maintain up to 35 days. The next placement can be without delay. There is less interruption for a shorter duration of menstruation. Tampons, spermicide nonoxynol-9, or intravaginal miconazole should not to be used at the same time.

It causes breast tenderness, headaches and nausea, spotting, vaginal intolerance or hypersecretion, and unconceivable loss or misuse. There are no studies evaluating its effect on adolescent bones. There is no evidence of VTE in relation to low-dose OCPs. Ease of use has not

They release EE 600 μg with norelgestromin 6 mg. They remain placed for 7 days for 3 consecutive weeks followed by 1 week without patch. It is a useful alternative method for women who hardly remember daily taking the pill because if they forget there is a 2 day error margin. It should be avoided when weight greater than 90 kg. The increased exposure to estrogen compared to oral contraceptive pills creates 1.6 and 1.2–2.2 higher probability of deep thrombosis [65, 66].

Existing progesterone: etonogestrel (3-keto desogestrel) 19-nortestosterone derivative.

It can be removed in less than 3 hours. It does not affect in sexual contact.

demonstrated increased compliance or prolonged use (<30% in 6 months) [64, 65].

that have made it possible to assess the benefits and risks that may have arisen.

greater risk for thromboembolic events [62, 63].

rone ring study 15–20 μg EU + 150–200 μg nestorone).

possible to be removed during sexual intercourse.

**11.4. 4th generation contraceptive pills**

200 Family Planning

**11.5. Contraceptive vaginal ring**

**11.6. Evra patch contraceptives**

They modify cervical mucus (viscosity in reduced amount) prevent sperm penetration and suppress endometrial growth which becomes inappropriate for implantation.

It is an ideal contraceptive method for teenagers who do not want to deal with contraception often [65].

#### **11.8. Injectable contraceptive preparations**

Injectable contraceptive preparations medroxyprogesterone acetate depot, intramuscular protection 3 months with efficacy 99.7%.

Monthly combined contraceptives estradiol cypionate and medroxy progesterone acetate depot, valerian estradiol, and norethrone acetate.

They improve dysmenorrhea increase the risk of thromboembolic events and may cause menstrual disorders [65].

#### **11.9. Transdermal contraceptive patches evra**

Transdermal contraceptive patches evra release ethinyl estradiol 600 μg with norelgestromin 6 mg. They remain placed for 7 days for 3 consecutive weeks followed by 1 week without patch it is a useful alternative for women who hardly remember daily taking the tablet because if they forget there is a 2 day error margin. They should be avoided when weight of the woman is greater than 90 kg. There is an increased exposure to estrogen compared to oral contraceptive pills 1.6 and 1.2–2.2 with higher probability of deep vein thrombosis [65, 66].

#### **11.10. Subdermal implants**

They modify cervical mucus (viscosity in a reduced amount), prevent sperm penetration, and suppress endometrial growth which becomes inappropriate for implantation. It is an ideal contraceptive method for teenagers who do not want to deal with contraception often [65].

#### **11.11. Injectable progestogens**

Injectable progestogens contain depot medroxyprogesterone acetate, intramuscular site of injection and they offer protection for 3 months with efficacy 99.7%.

Combined oral contraceptive pills estradiol cypionate and depot medroxyprogesterone acetate, valerian estradiol, and norethrone acetate.

They improve dysmenorrhea, increase the risk of thromboembolic events, and may cause menstrual disorders [67].

#### *11.11.1. Barrier methods*


From contraceptive barrier methods, the most widespread, economic, easy to use, well accepted by both partners, with the greatest contraceptive success and the greatest protection against sexually transmitted diseases is the male condom, 75% of adolescents report using a condom with a failure rate of 18% [68].

Finally, it protects woman in perimenopausal and postmenopausal periods who are under hormonal replacement therapy with estrogens from endometrial hyperplasia indicated in

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Contraindications conclude pelvic inflammatory disease. HIV and immunosuppressant are not contraindications. Risk of expulsion in women of reproductive age is 3–5% and in ado-

From the above mentioned, we conclude that with the preventative gynecological control in females of young age, a prompt diagnosis and appropriate treatment, in particular congenital abnormalities of the genitals and investigation of clinical symptoms of these individuals, can

Early diagnosis and treatment of ovarian tumors despite their small incidence of genital cancers up to 18 years of age is of major clinical importance because they are not always accom-

Many thanks to **Professor Efthimios Deligeoroglou**, Head of the Division of Pediatric— Adolescent Gynecology and Reconstructive Surgery, Cherman of 2nd Department of Obstetrics and Gynecology—Medical school, University of Athens, Aretaieion Hospital, Greece for his scientific support due to his great experience and knowenlege in this area. Many thanks to **midwives (Mrs Maria Strofali and Mrs Stavroula Falaga)** of family planning center, Democritus University of Thrace, Greece for their clinical support and examina-

, Bachar Manav1

and Georgios Galazios1

, Anna Chalkidou1

,

,

, Zacharoula Koukouli1

\*, Theodora-Eleftheria Deftereou1

2 Department of Obstetrics and Mastology, Rea Hospital, Athens, Greece

1 Department of Obstetrics and Gynecology, Democritus University of Thrace, Greece

3 Technological Educational Institute of Athens, Department of Midwifery, Athens, Greece

, Anastasia Bothou2

\*Address all correspondence to: ptsikour@med.duth.gr

puerperium.

lescents 5–22%.

**12. Conclusion**

panied by a characteristic clinical picture.

**Acknowledgements**

tion of teenagers.

**Author details**

Panagiotis Tsikouras1

Xanthoula Anthoulaki1

Stefanos Zervoudis2,3, George Iatrakis3

be made.

#### **11.12. Intrauterine contraception**

Copper intrauterine device is the most effective reversible method of contraception in terms of cost-effectiveness which is the first method of contraception with a coil used in the world.

Mirena, which was released in 1997, is a type of intrauterine device with levonorgestrel that contains 52 mg levonorgestrel and yields 20 μg/24 h for 5 years.

They can cause amenorrhea or oligomenorrhea.

#### **11.13. Innovations**

Forming new IUD with less levonorgestrel that will be easily applied to nulliparous women (Femilis and Femilis slim) are under construction and they are another IUD without side arms, for easy adjustment to various sizes of uterus IUD (SPRM) (ulipristol).

Aims of intrauterine devices:


#### **11.14. Side effects**

The use of IUD can cause tempοrarily edema, headache, tenderness, depression and breast tenderness, acne or other skin lesions. There are may also be appeared: abdominal pain in the lower part of the abdomen, vaginal discharge, nausea, functional ovarian cysts and rarely spotting, especially in the first months [69].

#### **11.15. Mirena**

Mirena is an intrauterine device effective in relation to the main indication of its usage which is contraception. It could be also used as a reliable therapeutic method of menorrhagia. In many cases, reduce dysmenorrhea. It reduces the risk of pelvic inflammatory disease and ectopic pregnancies.

Finally, it protects woman in perimenopausal and postmenopausal periods who are under hormonal replacement therapy with estrogens from endometrial hyperplasia indicated in puerperium.

Contraindications conclude pelvic inflammatory disease. HIV and immunosuppressant are not contraindications. Risk of expulsion in women of reproductive age is 3–5% and in adolescents 5–22%.
