WOMEN GYNACOLOGY-PART III- FEMALE HYPOGONADISM-TREATMENTS

FEMALE OVARY DEFECTS-INFERTILITY-TREAMENTS-I

Female hypogonadism is a major cause for infertility.This can be a birth defect and it may be a major defect for a female baby.It will be a cause not only for female infertility but also for many physiological defects when the child grows.

In several conditions from the birth,or somewhere in a growing age by genetics or by an accident,the female parts mainly ovaries do not develop and puberty the age at which the child begins to feel as she is a woman does not occur 

Turner's syndrom is a condition in which the overies not formed properly and there is a dysgenesis of ovary the growth of the child stops to make the child to appear like a dwarf.
Estrogens such as estradiol orally or by injections in apporopriate preparations are used to treat the ovarian dysfunctions and to bring the puberty.
Androgens and growth hormone should be used in an appropriate manner to treat the dwarfism.
The symptoms of puberty replicates,the genital structures grow into normal,and the body assumes the normal feminine contour.
Hypopituitarism,the deficiency of anterior pituitary also cause ovarian dysfunction in the child hood.
Thyroid and adrenal cortex deficiencies,may also be a cause for ovarian underdevelopment.The treatment regimen should be the replacement therapies of the appropriate hormones of deficiency.
But in all the cases estrogens should be included to treat the sexual under development.
Administration of growth hormone will bring back the normal adult stature.
Estrogen along with androgen given at normal puberty age can induce a shorter growth.
Dysfunctional uterine bleeding and dysmenorrhea has been treated in earliar days by estrogens alone or in combinations with progesterone as in oral contraceptives.
Girls suffering from unwanted pimples and acne has been treated with oral contraceptives which contains estrogen combination with progesterone.The androgens produced by the ovaries,which causes the acne would be suppressed by estrogens.Also the same treatment can be used to treat hirsutism a condition in which unwanted hair growth like mustache and beard in women.
Estrogen now clinically Used
1.Estradiol(Estrace)
2.Conjugated estrogens (Premarin)
3.Ethinyl estradiol (Estinyl)
4.Quinestrol
Clinical Uses
1.Hypogonadism,under activities of ovaries
2.As Oralcontraceptives
3.Hormon replacement therapy. 
Route of administration Transdermally,intramuscularly and orally
Side effects
1.Post menopausal bleedings
2.Endomerial hyperplasia
3.Breast cancer
4.Cholestasis
5.Prolonged use may cause High Blood Pressure,Thromboembolism,liver cancer.
Estrogens should not be used in the following events:-
1.Breast cancer
2.Pregnancy
3.Liver disease
4.History of thrombophlebities. 

WOMEN GYNECOLOGY-PART-V--FEMALE SEX PROBLEMS-TREATMENTS

DELAYING AND INDUCING THE LABOUR AND ABORTION

THE UTERUS OR WOMB

The above picture shows the entire female genitalia with arrow marks to indicate the parts.
The arrow marked A is the Uterus or Womb which serves as the carrier bag to protect the fetus for the entire duration of pregnancy normally of 266 to 300 days.Inside the uterus the endometrium the inner linings of the uterus become a cushion bed which has been nicely developed for luxurious stay of the fetus indicated by an arrow marked E in the above picture.This endometrium is developed and protected by an hormone from the corpus luteum of the ovary known as Progesterone the hormone of Pregnancy as it along with corpus luteum would be ceased either at the end of the pregnancy period or at the end of the menstural cycle if no fertilization resulted
The Uterine muscles are composed of pace makers similar to heart muscles wih a power of auto electrical contractive stimulus.The pace makers would automatically trigger the stimuli normally at the beginning and slowly increasein intensity and become strong at the completion of the normal pregnancy period of 266 to 300 days.The stimuli produce waves of contraction.The waves would easily be conducted through out the uterine muscles by the low contraction resisting cell gaps with rhythm.These cell junctions would be increased in number and maintained by the progesterone and estrogens as the pregnancy period grows into later trimesters.
Oxitocin a hormone from the posterior pituitary will be released throughout the pregnancy period.The hormone is a powerful contractor of uterine muscle will act on it to give a final strong stimuli to induce the labour for delivering the baby.
Eventhough the secretion of oxitocin is constant from the pituitary all the times and throughout the pregnancy period but the responsiveness of the uterine muscle to oxitocin is gradual.Slow at the beginning of the pregnancy period and peak at the last trimester.
Any pathalogical condition which disturb this system would result in abortion.
Abortions can be manually induced or prevented by treatments at various situations.
Drugs That Induce Abortions
1.Oxitocin (Exoginous)
2.Prostaglandins (PGE-2,PGF-2a,15-methyl PGF-2a
3.Ergot Alkaloids (Ergonovine)
Drugs That Delay Uterine Motility
1,. Magnesium sulphate;
2.b-2adrenergic agonists 
3.Ca-2 blockers
4.Prostaglandin synthetase inhibitors..
Induction of Labour
In situation such as Diabetes Mellitus,Hypertension,Isoimmunization,Intrauterine growth defects,and placental defects the continuation of pregnancy may become risky to the mother or baby more than the delivery.
Before the pharmacological induction is carried out various things should be considered such as the fetal maturity,the fetal position,fetal distress,placental abnormalities,and previous uterine surgery.
The drug of choice for inducing labour is Oxitocin.A dilute solution of oxitocin can be infused intra venously as a slow infusion to induce a safe labour as 10 milliunits per ml.The procedure should be with gradual increase of the dosage by starting with 1 milliunit/ml and gradually increase for every 30 minutes and maintain at 4 milli unit /ml.for atleast 1 hr before bring it to the optimum dosage of 10 milliunit/ml
During the entire procedure trained persons must be engaged and uterine activities should be carefully watched.
It contractions are forceful and violent wih increased frequencies or alarm signals raised for a tired muscle cells the infusion of oxitocin must be immediately stopped.
Fetal discomfort can be easily estimated with its cardiac beats.
If there is a tetany like uterine contraction it should be relaxed by the use of a b-2 adrenergic agonist such as terbutalin.
To avoid undesirable side effects the terbutalin should be given as slow subcutaneous injection.
When the progression of labour becomes normal the rate of infusion of oxitocin should be minimised or stopped as per the need.The infusion should be maintained at the lowest possible rate inorder to maintain an adequate progression of labour.
When employed in term oxitocin induce labour in majority of cases.
Amniotomy the artificial ruputing of fetal membranes along with oxitocin can also be used to induce labour.These procedures should be done with experienced obstetricians to avoid fetal distress.
Augmentation of the Labour.
If augmentation of the labour proceeded normally in that case infusion of oxitocin is not necessry and should not be used.
In normal labour the force of normal contraction of the uterus should not be disturbed by drug induced augmentation as this will make incoordinaed force full contraction of the uterus against partially dilated cervix and may causes uterine rupture,severe laceration of the mother,trauma of the fetus,and a tetany like contraction may compromise the pacental exchange and a disconnection of oxigen supply to the fetus.
In case of dysfunctional labour the labour can be augmented by an experienced obstetrician by the oxitocin successfully.Bu an unjustified and careless use of oxitocin may itself induce dysfunctional labour.
Therapeutic Abortion
If pregnancy is dangerous to the mother aborting the baby is prescribed to save the mother by the doctors.
Suction curettage is the method usually employed by the doctors to induce abortion.
Mifepristone a 19-norsteroid a progesterone antagonist is usually employed in this method.Mifepristone when  administered along with prostaglandin can induce 99%abortion at early pregnancy.Also in early pregnancy a combination of mifepristone along with methotrexate, and misoprostol can induce 96% abortion .
Beyond the first week of he second trimester there are so many options are available to induce abortion.Intra amniotic injection of a hypertonic sodium chloride (20%) are used with many failures and this produces follows several potential hazards of hypertonicity.
Vaginal suppositories of PGE-2 (Dinoprostone and Prosten E-2) has been inserted into the vigina with the intervals of 3 to 5 hours has been tried successfully.
In circumstances such as if still the uterine cantent are not eliminated completely but uterus is ruptured the intramuscular injection of 0.25 mg of carboprost tromethamine,a 15-methyle PGE-2a Hemabate) has been proved effective.Subsquent doses of 0.5 mg can be given with 2 hrs intervals.Nausea and vomiting are the side effects of these prostaglandins.
Intra vajinal suppostories of misoprostol also can be tried for every 12 hours.
After abortion whether its auto or induced abortion the bleeding should be controlled similar to normal labour procedures by ergonovine and oxitocin.

Delayed Labour

Drugs are used to delay the labour by inhibiting uterine contractions in the following situations:-

1.To prevent premature labour.

2.To carry out other therapeutic measures

Drugs that are used in this procedure are called as Tocolytic agents:-

1.Magnesium sulphate

2.b-2 adrenergic agonists

3.Calcium channel blockers

4.Prostaglandin synthetase inhibitors.

Some patients may well respond to bedrest to prevent early contractions of the uterus.If not only tocolytics should be tried.

The delayed labour should be equally weighed between its advantages and risks.In general the use of tocolytic agents are reserved for those pregnancies where the gestational age is greater than 20 weeks and less than 36 weeks.A child born within this range of pregnancy period is considered as premature.

Before starting the drug therapy a consideration must be made with a minimal dilating requirement of cervix is less than 4 cm.and cervical effacement(the thinning of the cervix) is less than 80%.

Contraindications to tocolytics 1.Rupture of uterine,cervical or amniotic membranes 

2.Eclampsia,a condition in which convulsions occur in a pregnant woman with high blood pressure

3.Preeclampsia,a condition of eclampsia with organ damage such as kidney in high blood pressure.

4.Chorioamnionitis Infections of the fetal membranes the chorion and amnion.

5.Premature detachment of placenta

6.Fetal distress.

b-2 Adrenergic Agonists

1.Ritodrine (FDA approved to delay labour)

2.Terbutaline 

Ritodrine hydrochloride(Utopar)  is available for oral and i.v. injections

Ritordine HCl is slowly infused at the rate of 0.1 mg/min and if tolerated the rate is further increased by 0.5/min for 10 min and further increased to a maximum of .035 mg/min until labour is controlled.Once attained the controll the infusion is continued usually for 12 hrs at the rate attained.

Oral adminisration should be stared before 30 min of the termination of the infusion by 10 mg per every 2 hours for the first 24 hrs.followed by 10 to 20 mg per every 4 to 6 hrs.The total daily dose should not exceed 120 mg.

Terbutalin (Bricanyl) should be given orally 2.5 to 5 mg every 6 hrs and intra venously at 10 to 80 mic.gm/min and subcutaneosly at 0.1 to 0.4 mic gm /min for 1 to 4 hours.

WOMEN GYNACOLOGY-PART-II-FEMALE SEX HORMONES

FEMALE SEX HORMONES

Steroids are the chemical compounds in which the structural formula is composed of peculiar four membered rings namely A,B,C,and D resumbles that of a compound known as cyclo pentano perhydro phenantherene 

In our body all the male and female sex hormones are produced from cholesterol which is a steroid and hence all of them have the steroid structure in their molecules.Among these steroids body can convert one from other as per the need very easily by simple sructural modification.The female sex hormones are all seroids with an aromated phenolic A ring.Hence aromatization of a male sex hormone (Androstenedione) at the A ring will result in the conversion to female sex hormone (Estradiol,the main estrogen in our body) by our body out side ovary.

Our body is secreting in the ovary three female sex hormones namely Estradiol,Estrone,and Estriol.Out of these estradiol comprises the major part.

Esradiol is the main estrogen secreted by our body in the ovary in equillibrium with estrone.Both estradiol and estrone are finally convered to estriol before excretion.

For oral ingetion as estradiol is 100% deactivated by liver on first pass,to prevent this there are esterified semisynthetic estradiols are available for oral contraceptive use.They are Ethinyl estradiol,Mestranol
For intra muscular injections semisynthetic esters like estradiol cypionate and estradiol valerate are highly active as these esters are slowly released from the muscles to give prolonged contraceptive actions
There are nonsteroidal estrogens are available such as diethyl stilbestrol,dienestrol,chlorotrianisene.These non steroidal hormones are nowadays less atractive in use.
Pharmacological actions of Female sex hormones
The specificity of estrogen actions are at the estrogen receptors on estrogen sensitive organ tissues such as vagina,uterus,mammary glands,anterior pituitary and hypothalamus.Estrogen receptors are all nuclear receptors and hence when estrogen bind to the receptor it become a complex with it and enter into the cell and attach with the DNA of the nucleous and exhibit its actions like anabolism or catabolism or enzyme synthesis.One best example is estrogen act on bone receptors and inhibit bone resorption and stimulate new bone formation.It act on kidneys and increase the production of an enzyme,hydroxylase which convert vitamin D to D-3.
On lipid metabolism estrogens slightly increase triglyceride and HDL levels but decrease LDL and total cholesterol.
Uses
1.As contraceptives (combined with progesterone)
2.Treatment of menopausal syndromes such as:-
a.Vasomotor disorders.
b.Urogenital atrophy
c.Psychological disorders 
3.Acne
4.Osteoporosis both senile and postmenopausal
5.Prostate cancer
Toxicity
1.GI distress like nausea,vomiting anorexia and diarrhea.
2.Cardiovascular effects like high blood pressure,thrombo embolism,stroke amd heart attack.
3.Fluid retension
4.Hypertriglyceridemia
5.Endomerial (Uterine) Cancer on prolonged use only
6.Liver cancer on prolonged use only
 

WOMEN GYNACOLOGY-PART-I

FEMALE OVARY SYSTEM

INTRODUCTORY

Basically the female sexual system differs from male sexual system by the separation of the genital pathways from the urinary path ways where as in males both are united at the outlet level to form a combined urino-genital system.Here we will see the entire pharmaco-gynaecology of women comprehensively in parts by parts.

 Ovaries are major female reproductive parts situated at either side of the trunk embedded in the pelvic cavities of the female as tiny glands.These glands composed of tiny follicles known as Graafian Follicles.They are the main secreters of the female sex hormones known as estrogens.
The estrogens are mainly responsible for all changes at the age of puberty of the females and account for the secondary sexual characters of the females.
The direct action of estrogens causes the healthy development of the ovaries,fallopian tubes,uterus vajina and breast.
Also estrogens causes the shiny and soft female skin and structrure by evenly distributing the fat of the body.
Neuroendocrine Regulations of Mensuration
The hypothalamus which is situated at just below the thalamus in the brain secretes a hormone known as Gonadotropin Releasing Hormone (GnRH) in a pulsative manner.Then the GnRH act pulsatively on the anterior pituitary and stimulate it to release pulsatively the Gonadotropic Hormones or Gonadotropins which are the two hormones similar to male,the LH(the leutinizing hormone) and the FSH (the follicle stimulaing hormone).These two hormones act in a pulsative manner on the ovaries and causes the maturation of the follicle into ovum,and the secretions of the ovarian hormones estrogens and progesterone.
Progesterone exert a feed back mechanism on hypothalamus and pituitary whereas estrogen is having a feed back mechanism on pituitary only.
The full development of the follicle into ovum takes a theorital period of 11 to 14 days which is the mid cycle of the menses.At this this point the matured ovum detach itself from the ovary and enter into the fallopian tube and wait their for fertilization by a single spermatozoa.The ovum's life time is only 24 hrs whereas the sperm's life time is 72 hrs.The empty space occuppied by the detached ovum develops into a yellow gland known as Corpus Luteum which begins to secrete more progesterone and estrogen by the action of LH which  by feed back mechanism stop the stimulation of the overy further by the hypothalamus pituitary axeses until the cycle ends with fertilization or empty completion.If the ovum get successfully fertilized the progesterone and the corpus luteum will function throughout the entire period of pregnancy to protect the fetus.If not during the next half the cycle the corpus luteum begins to caese.The progesterone prepare the endometrium of the uterus like a cushion convenient for the reception of the fertilized ovum into it for stay.If no fertilization at the end of the period the entire things whould be shed off as menses.Then the next cycle would be resut.In the entire process the secretions of the steroids from the hypothalamus and pituitary axes must be pulsative with a regular intervals otherwice a continue secretion may cause continue stimulation of the ovaries which will result in painfull amenorrhea.

MALE HYPER GONADISM-TREATMENTS

ANTI ANDROGENIC TREATMENTS

Anti androgenic treatments are options prescribed for the treatments when androgens are over dosed and the male sex organs are over powered to precipitate so many unwanted serious and non serious side effects.

If androgens are administered carelessly without a doctor's supervision the following side effects are observed.

1.Over musculinization

2.Over virilization

3.Hirutism in women

4.Depression of menses,acne and clitoral enlargement

5.Rarely hepatic adenomas and carcinomas

6.Cholestatic jaundice

7.Prostatic hyperplasia. 

Anti Androgens

1.Gonadotropin Releasing alalogues:- Leuprolide or Gonadorelin

This drug is available as subcutaneous daily dose injection and should be prescribed by a doctor and given by him in his office.This drug resembles structurally similar to the hypothalamus gonadotropin releasing hormone and imitating it and thereby suppressing the release of gonadotropic hormone and thereby inhibiting the gonads.At the inistial state it may incease the levels of LH and FSH the two gonadotropins,but on continuation of the treatment it will suppress their levels 

Mostly used in Prostate enlargement

2.Receptor Inhibitors:- Cyproterone  Bicalutamide and Fluamide

It is a non steroidal synthetic androgen receptor blocker mostly used for treating Prostate Cancer.

Also can be used to treat hyper androgenic actiivity and hirutism in women.

 Bicalutamide is a newer medicine and because of its more convenience and lesser side effects it mostly replaces Flutamide.

3.Steroid synthesis Inhibitors:- Ketaconazle,and Spinolactone(Aldactone)

4.5-a-Reductase Inhibitors:-Dutostride and Finastride

These drugs can be taken orally according to doctor's advise.They inhibit the conversion of the less active testosterone into the more active dihydrosterone by inhibiting the enzyme 5-a-Reductase. 

MALE INFERTILITY-TREATMENTS -PART -II

MALE HYPOGONADISM-TREATMENT OPTIONS

We have already seen in the last post a normal healthy male has  well developed male sex organs as he receives proper androgenic expression from the second month of his fetal life in his mother's womb.The developing testes in the fetal life also produce another poly peptide hormone known as Mullerian Inhibiting Hormone that

inhibit the development of the Mullerian Duct in the fetus.In this stage Testosterone act subsequently,on the Wolffian ducts and differentiate it into the epididymis,vas deferens and semen vesicles.

On the other side dihydrotestosterone causes fusion and elongation of the labioscrotal fold to form male urithra,penis,and scortum and virilize the urogenital sinus to form the prostate.

After doing these works the plasma concentrations of androgens begins to decline and at birth it is essencially undetectable in the baby's blood.

At the age of puberty the androgens will magically reappear in the blood and act directly on the testes to produce male puberty signs.

Lack of sufficient androgen secretions at the fetal life will result in male sexual insufficiency or Male Hypogonadism in later life.

Symptoms of Male Hypogonadism

1.Underdevelopments of the male sex organs

2.Feminism-Female characters because of the estrogenic effects like soft voice,soft and shining skin with evenly distributed fat throughout the body etc.

3.Absence of virilzation

4.Absence of puberty

5.Declined spermatogenesis results in male infertility

6.Impotence

7.Weight Loss

8.Anemia

Unfortunately all the above defects can be corrected by the androgen replacement therapies except the declined sperm production for which upto date there are no known guaranteed therapies.

Androgens have two effects such as Andrgenic and Anabolic accordingly they can be divided into two as per their purposes of use as follows

1.Androgenic Androgens

 These androgens are used to produce purely androgenic effects in those individuals who suffers hypogonadal functions.Eventhough they have considerable anabolic effects that can be undermined are can be used for added benefits.

(e.g)1.Testosterone injections

        2.Esters of testosterone for oral use such as testosterone-17-enanthate (Delatestryl) is a long acting one

        3.Methyl testosterone or fluoxymesterone a potent orally acting testosterone ester.

2.Anabolic Androgens

These compounds are mostly synthetic or structurally modified testosterones in order to abolish the unwanted androgenic effects.

(e.g) 1.Oxandrolone (Oxandrin)

         2.Stanozolol (Winstrol)

         3.Fluoxymesterone

         4.Nandrolone phenylpropionate (Durabolin)

Causes of Male Hypogonadism

Testosterone by itself not active in all tissue receptors to produce the male functions unless it is converted into the more potent dihydrotestosterone.There are two enzymes present in our body for the conversion of tesosterone as follows

1)5-a-reductace-1 This enzyme is present in all the non genital skin and liver.Any damages in these areas may result in the lack of this enzyme and cause hypogonadism in spite of the testosterone production is normal

2)5-a-reductase-2 This enzyme is present in the skin of the genitals and the urogenital pathways.Any disease or damages may result in suppression of this enzyme and causes male hypogonadism  
Treatments for both hypogonadism and anabolic therapies are all subjected to be under Doctor's supervision.Since all the above mentioned androgens as either androgenic or anabolic

 are all hormones with serious side effects.
Side effects of Androgens
1.Over musculinization
2.Extra virilization in male
3.Hirutism in women (mustache and beard formed)
4.Depression of menses,acne and clitoral enlargement.
5.Rarely liver carcinomas and adenomas
6.Cholestatic jaundice
7.Prostate enlargement.

MALE SEXUAL DEFICIENCY AND INFERTILITY-TREATMENTS

MALE SEXUAL DISORDERS-MALE INFERTILITY

Sexual disorders and infertility are not uncommon in both male and female in modern days.These defects are frequently correlate with our diet,lifestyle,and emotional atmosphere.Stress and diet are playing important roles for hypogonadism the sexual dysfunctions of the male and female gonads followed by diseases and other organal disorders.In this post we concentrate about male sexual problems such as infertility,impotence and over activity of the sex organs.

The Hormones Of Sex in Men

There are variety of sex hormones are produced in men by various organs such as testes,the male sex organs prostate adipose tissues and adrenal glands.The predominant and the active forms are testosterone and dihydrotestosterone secreted by testes.These two hormones are accounting 99% male sexual characters.Out of these two hormones the dihydrotesosterone is more powerful and produce variety of androgenic reactions in our body.The most unwaned effect of his hormone is the enlargement of prostate gland and we will not deal with this here.

Testis also produce Androsterone,Androstenedione a testosterone metabolite.Androsterone is a weak horemone and its role of male sexual nature is negligible and it is formed by metabolizing dihydrotestosterone..The precursor hormone androstenedione will be converted into testosterone by peripheral tissues as per the need.

Adrenal glands also secretes in small amount of a male sex hormone known as Dehydroepiandrosterone which is also not very active.

There are metabolites of dihydrotestosterone  known as 5-a-androstane-3-a,17-beta-diol,and androsterone which are also weak in action.
In out side the testes some tissues especially brain tissues metabolise testosterone into female sex hormone the estradiol in men which is accounting and giving calmness and closure of the penis in resting periods most probably after a coitus or ejaculation.Esradiol is produced by testes also.Approximately 50 mic grams of estradiol is produced in normal man.Overproduction may result in feminism in men.
For treatments of hypogonadism it is found to be moral to administer Testosterone either by mouth or by other routes according to above studies.But the problem is the liver which readily metabolize testosterone 100% on administration by any route and inactivate it.To prevent this there are oral and pareneral preparations testosterone which is esterified to protect it from inactivation.These esters when they pass liver they get metabolized by liver and release testosterone into the circulation without inactivation.Oral testoserone and dihydrotestosterone are not effective than injections.
Recent findings have given an advantage oral preparation of modified testosterones such as methaneolone acetate and testosterone undecanoate.and these orally successful.
In oral preparations fluoxymesterone is a good androgen but a poor precursor of estrogen
But 19-nortestosterone is as strong as dihyrotestosterone in androgenic effects. 

SYNTHESIS AND SECRETIONS OF MALE SEX HORMONES

Testosterone in plasma usually occurs at high concentrations usually in three phases of life.

1.At the embryonic phase in this stage the plasma testosterone beginst to appear when a ovum is fertilized as a male embriyo and rises day by day reaches its peak high level at the eighth week and declines to bottom at the time of delivery.

2.At the neo natal period. After the birth it sarts again to reach its peak level at neonatal period of about one year and decline to bottom at the age pre-puberty.At puberty the pituitary hrough the hypothalamus secretes two hormones known as Luteinizing Hormone(LH) and Follicle Stimulating Hormone (FSH).

Gonadoropins begins to secrete in a pulsative manner as puberty progresses during both sleep and wake positions.During puberty the hypothalamus and pituitary both respond to the feed back mechanism of gonadotropin secretions very weakly.

Prior to puberty when the organs not well matured the plasma concentration of testosterone in a male 20 ng/dl.(0.7 nM)

as the puberty progresses the secretions also correlate with it and the male reaches the adult age the plasma concentrations of the testosterone is 300 to1000 ng/dl(10 to 35 nM) and the rate of production is 2.5 to 11 mg per day.In plasma 40% of the testosterone are bound to androgen binding globulin,58% are bound to other plasma proteins.2% is free in plasma which contributes to the androgenic activity.
Albumin bound testosterone is dissociating in the capillary bed for ready entry into the cells for actions.
LH and FSH from pituitary are regulating the development of testicles,and the production of sperm.Growth hormone also synergize the activities of LH and FSH.Estrogens suppress the LH action and reduce the secretion of testosterone.
Testoserone is a steroid and it is synthesized from cholesterol by the testes by the stimulating effect of pituitary LH on the Ledig cells of the testes.FSH on the other hand stimulate the seminiferous tubules to produce sperm.FSH also has an augumenting effect on LH.The spermatogenetic effects of both LH and FSH are all through the production of testosterone.
The injection of Human Chorionic Gonadotropin represents only the effects of LH. 
Administration of testosterone to men with hypogonadism and men who have been castrated(Eunuchism) is affecting the functions of LH and FSH.
In normal man estradiol is produced by testes and as well as brain.Brain and other tissues are converting a fraction of male sex hormone o female sexhormone the estradiol in a similar manner to testes.15% of he estradiol secreted by testes in a normal man.
In normal man the adrenal cortex is producing a minor quantity of testosterone through its precursor androsenedione but is not sufficient to represent the male nature.But in case of adrenocortex hyperplasia or cancer the production will be large.
Physiological effects of Male Sex Hormones
Androgens at the embroyanic age minutely secreted by testes and adrenal cortex withou any pituitary stimulation is virilizing regulating and maintaining the male urogenital parts of the male embryo.
In neo natal age they help the sexual developments within the central nervous system
At puberty they help the boy to become a well developed adult man.At this age the testes begins to enlarge.The penis and scortum start to grow,and pubic body hair beard and mustache begins to appear.Early in puberty,penial erections,nocturnal ejaculation and masturbations are frequent in most boys.
At the same time the growth promoting nature of the androgens contribute to increase in height,well established bone structure and musculin protein anabolic developments will leads into increase in height and weight.Physical vigor is increased.Testes developed into its full size.The skin become thick and oily.More proliferated sweat glands which are prone to plugging ang infections which results in pimples and acne formations.
Subcutaneous fat is lost and the veins under the skin appear prominently.Voice becomes deep. 
Secondary sexual characters begins to appear.
Heriditary appearance like baldness may begins to start like recession of the hairline at the temples and thinning of the hair at the crown.
At the end of this stage the bone growth attains to end.After this a further 1 or 2 cm growth is possible.
On behavior also androgens have major role.Men's aggressive rough and rude behavior are all due to androgens.Administration of male sex hormones may definitely influence the mood of a normal individual.These are the bases for treatments of male insufficiency with androgens.
When androgens are given to an prepuberty boy or a eunucoid young man the events of normal puberty are duplicated but there may be a time of laps (1 to 2 or more years) may take to establish the full virilization.
Shortly after starting the treatment inapropriate  erections with embarrassing frequencies may begins to surface with discomforts.Tolerance will develop as the treatment continues and these discomfort will be eased and subsided.Increased physical vigor and a general feelings of wellbeing ensued after a few weeks of the treatments.
The penis begins to grow followed by a distinct change in the voice.
Auxillary and pubic hair become more luxuriant.
The rapidity of the skeletal and muscular growth is very impressive in boys treated at or before the time of normal puberty.
The height growth increase 10 cm or more during the first year of treatments followed by diminishing for next 2,3 years.
With continued treatment development with the growth of a beard and body hair as a late expression of therapy.

Actions of Androgens On Normal Male

Normally,at the second month of the fetal life androgens start to be secreted by the baby's testicles and establish their important role of differentiation and development of the male reproductive system.