Sex H or mones

Dr. Khaled Obad

2023
 Sex Hormones

SEX
HORMONES

Female Male
Hormones Hormones

Androgen
Estrogen Progesterone
Testosterone
 Estrogen

 The estrogens are produced by the ovaries, placenta and in small

amounts by the adrenals, testes and by peripheral aromatisation of the
androgens.
 During the first part of the menstrual cycle, estrogens are produced by
the granulosa cells by aromatisation of the androgens derived from theca
cells in the ovarian follicle.
 The major estrogens are estradiol, estrone and estriol .
 Estrogen types

:Estrogens include
.Natural estrogens. Estradiol, estrone, estriol .1
.Synthetic estrogens. Systemic—ethinyl estradiol, stilbestrol, mestranol .2
.Topical—dienestrol •
SERMs Tamoxifen, Raloxifene, Toremifene, Ormeloxifene, .3
.Clomiphene, Fulvestrant
 Estrogen receptors

 Estrogen receptors are nuclear receptors and

are of two types. ER Alpha and ER Beta .
 Distribution:
 ER Alpha—female reproductive tract, breast, blood vessels and
hypothalamus.
 ER Beta—ovaries and prostate.
 Estrogen Actions
:Actions: Estrogens are required for
.The normal maturation of the female reproductive tract .1
.Development of secondary sexual characters in the female .2
Metabolic effects: Estrogen promotes retention of sodium, nitrogen and fluid in the .3
.tissue
Integrity of skeleton: Estrogens inhibit the resorption of bone and maintain the bone .5
.mass
Estrogens are important for the maintenance of normal structure of the skin and .6
.blood vessels in women
Estrogens decrease plasma LDL cholesterol and raise HDL cholesterol and .7
.triglycerides
8. Effect on blood coagulation—estrogens enhance the coagulability of the blood.
9. They stimulate protein synthesis in the brain and may thereby affect mood and
emotions.
 Estrogen Mechanism of action

1. Estrogens bind to estrogen receptors.

2. The estrogen—receptor complex moves to the nucleus and
binds to the estrogen response elements (ERE) which are present on
the target gene and bring about the synthesis of specific proteins
involved in the effects of estrogen.
 Estrogen Pharmacokinetics

 Natural estrogens are metabolised rapidly in the gut.

 All estrogens get absorbed through the skin and mucous
membrane.
 They are largely bound to plasma proteins (globin).
Estrogens
 are metabolised by glucuronide and sulfate conjugation in the
liver.
 They also undergo enterohepatic circulation.
 Estrogen Adverse Effects

1. Nausea, breast tenderness, migraine headaches, hyperpigmentation,

hypertension and cholestasis.
2. Cause postmenopausal uterine bleeding and endometrial hyperplasia.
3. Cancers.
4. Teratogenicity.
5. Dysmenorrhoea.
6. Dysfunctional uterine bleeding.
7. Carcinoma prostate.
8. Acne.
 Estrogen Uses

1. Replacement therapy
 In primary hypogonadism
 Postmenopausal syndrome
2. Senile vaginitis.
3. Osteoporosis.
4. Hormonal contraceptives.
5. Dysmenorrhoea.
6. In primary hypogonadism.
7. Dysfunctional uterine bleeding.
8. Carcinoma prostate.
9. Acne.
 Estrogen Preparations

Estrogens are available for oral and parenteral use. A transdermal patch
for cyclic estrogen therapy is available. Estrogen vaginal cream and
vaginal pessaries are also available. Conjugated estrogens are available
as tablets, injections and vaginal cream.
Cenestin is a synthetic conjugated estrogen available as tablets (0.625
mg) for control of menopausal symptoms.
CONJUGASE, ESPAUZ, PREMARIN 0.625 mg,
1.25 mg, 0.3 mg, 25 mg inj, 0.625 mg/g VG cream.
 Contraceptive

 Contraceptives are drugs, devices, or devices that release drugs that

are used to prevent conception, the fertilization of an egg by the
sperm and resulting pregnancy.
 Oral contraceptives (birth control pills) contain female sex
hormones that prevent ovulation. Most of the oral contraceptives
contain both an estrogen and a progestin, whereas a few contain
only a progestin.
 Contraceptive classification

1. Combined hormonal contraceptives (Estrogen with a progestin)

a) Oral pills
– Monophasic –Biphasic – Triphasic
b) Parenteral combined contraceptives
– Injectable
– Transdermal patches
– Vaginal rings
..Cont

2. Progestin only contraceptives

a) Oral—mini pill
b) Parenteral
– IM inj
– SC implants
3. Postcoital contraceptives
• Estrogen + progestin
• Levonorgestrel and Mifepristone
 Combined Hormonal Contraceptives .1

 Combined pills contain low doses of an Estrogen

(Ethinylestradiol and mestranol (in the dose
of 20–50 ug)) and a progestin (Norethindrone, Levonorgestrel,
---Drospirenone and a newer Desogestrel and Norgestimate).
 Oral combined Contraceptives

1. Monophasic contraceptives contain the same amount of

progestin throughout the administration cycle.
2. Multiphasic contraceptives increase the amount after 7 and14
days of the cycle. The amount of progestin is increased
in multiphasic preparations to mimic the natural ratio of
estrogen to progestin during the menstrual cycle.
 Oral Contraceptives mechanism

1. They prevent ovulation—by a negative feedback on the

hypothalamus.
2. Estrogens suppress FSH release by negative feedback on the pituitary.
3. Progesterone also inhibits estrogen-induced mid-cycle LH surge.
4. Progesterone renders the cervical mucus thick and unfavourable for
sperm penetration.
5. OCs alter the uterine endometrium making it unfavourable for
implantation.
6. OCs also adversely influence the coordinated contractions of the
cervix, uterus and fallopian tubes which are required for transport of the
ovum, sperm as well as for fertilisation and implantation.
 Oral Contraceptives uses

1) Prevent conception.
2) Treat acne vulgaris.
3) Dysmenorrhea.
4) Premenstrual syndrome.
 Oral Contraceptives Adverse Effects

Milder effects
 Headache. Migraine.
 Nausea, vomiting, edema, breast tenderness, amenorrhoea and
irregular menstrual cycles may occur
 Weight gain, acne, mood swings and hirsuitism may occur.
More severe side effects
1. Cardiovascular effects
a. Thromboembolic
b. Myocardial infarction:
c. Cerebrovascular disease:
d. Hypertension:
..Cont

2. Cancers
3. Cholestatic jaundice and gallstones
4. Impaired glucose tolerance
5. Depression
 Oral Contraceptives Contraindications

1. Thromboembolic and cerebrovascular disease

2. Breast cancers
3. Liver disease
4. OCs should be used with caution in diabetes, hypertension,
convulsive disorders, oedema and CCF.
 Oral Contraceptives Interactions

1. Carbamazepine, phenytoin, and other drugs that increase

the hepatic metabolism of oral contraceptives.
2. Antibiotics, including penicillins and tetracyclines, can eradicate
intestinal flora involved in the enterohepatic cycling of contraceptive.
3. Estrogens can inhibit the metabolism and potentiate the effects of
antidepressants, and glucocorticoids.
4. Estrogens increase the synthesis of vitamin K–dependent clotting
factors and may thereby antagonize the effect of warfarin.
 Oral Contraceptives preparations

Duration in days Estrogen + Progestin dose Regimen

1. Combined pills

days from day 5 of the menst. Cycle 21 EE 50 μg + Norgestrel 500 μg .1

days from day 5 of the menst. Cycle 21 EE 30 μg + Levonorgestrel 150 μg .2
Monophasic
days + 7 days of ferrous sulphate tab 21 EE 30 μg + Levonorgestrel 300 μg .3
days + 7 days of ferrous sulphate tab 21 EE 20 μg + Desogestrel 150 μg .4
 Oral Contraceptives preparations

Duration in days Estrogen + Progestin dose Regimen

1. Combined pills
days 10 EE 35 μg + Norethindrone 500 μg .1 b. Biphasic
Next 11 days EE 20 μg + Desogestrel 150 μg .2
EE 30 μg + Levonorgestrel 50 μg .1
Day 1–6
EE 40 μg + Levonorgestrel 75 μg
Day 7–11
EE 30 μg + Levonorgestrel 125 μg c. Triphasic
Day 12–21
EE 35 μg + Norethindrone .2
days 7+7+7
and 100 μg 75 ,50
 Progestin Only Contraceptives .2

1. Mini pill: A low dose progestin is taken daily without a gap (75 μ g
norgestrel).
Estrogen and its accompanied long-term adverse effects are thus
avoided, but efficacy is lower, menstrual cycles may be irregular and
is, therefore, not popular.
..Cont
2. Progestin injections: Depot preparations contain a progestin and
are given as:
1. Intramuscular injections at 3–6 months intervals, e.g. depot
medroxyprogesterone acetate (DMPA) 150 mg every 3 months
injected IM
 Ovulation is inhibited for about 14 weeks.
 Long-term use of DMPA reduces menstrual blood loss. The risk of
endometrial carcinoma is also reduced.
3. Subcutaneous implants: They are implanted under the skin.
Capsules containing norgestrel are (NORPLANT capsules)
implanted subcutaneously in the forearmor upper arm.
 Emergency Contraceptives

 Drugs that are available to prevent pregnancy after unprotected sex are called
emergency contraceptives.
 Preparations containing levonorgestrel are also available with or without
prescription for use as an emergency (postcoital) contraceptive in women who
have not been taking another contraceptive.
 These preparations consist of a either a single 1.5-mg dose of the progestin
levonorgestrel , or two 0.75-mg doses, with the first dose taken within 72 hours
of intercourse and a second dose taken 12 hours later.
 Use of an emergency contraceptive usually causes nausea and vomiting that can
be reduced by administration of an antiemetic agent (e.g., promethazine). It can
also cause headache, dizziness, legcramps, and abdominal cramps.
 Drugs for infertility

1. Clomiphene
A) Mechanism of action
Clomiphene blocks ERs in the hypothalamus and pituitary and prevents estrogen’s
feedback inhibition of gonadotropin secretion. This increases FSH and LH secretion,
which induces ovarian follicle development and ovulation.
B) Uses
1. Infertility: Clomiphene citrate is used in infertility due to ovarian disorders. given
orally, 50 mg daily for 5 days starting from 2 to day 6 of the cycle; course may be
repeated for a few cycles till ovulation occurs.
C) Side effects
include ovarian hyperstimulation resulting in multiple pregnancy, ovarian cysts, hot
flushes, headache and skin rashes. It could also increase the risk of ovarian tumours.