The Ovaries: Reproduction and Endocrine Function

The Ovarian Follicle: Reproductive and Endocrine Organ

The female body is endowed with the uterus and ovaries as reproductive organs.  But having babies is not their only function. Initial breast bud and pubic hair formation occurs because of hormones produced by the ovaries.  Later, a girl will have her first period.

A girl begins to menstruate because her ovaries are producing estrogen and progesterone.  The 28-day menstrual cycle may not begin with the first period.  It may take 2-3 years for a girl to be ‘established’ with monthly periods, as she may have her periods only once or twice in the first year, then more often as time progresses.

Women are born with two ovaries, one on each side of the uterus (See Figure 1).

Figure 1.  The female pelvis.  The uterus is behind the urinary bladder.  1 = Fallopian tube; 2 = urinary bladder; 3 = pubic symphesis; 4 = vagina; 5 = clitoris; 6 = urethral opening; 7 = vagina; 8 = ovary; 9 = fascia; 10 = uterus; 11 = posterior cervix; 12 = cervix; 13 = colon; 14 = rectum.

It is important to understand that the human ovary serves two functions:  reproduction and endocrine.  Both of these functions are tightly coupled, as the release of hormones makes the uterus ready for fertilization of an oocyte that comes from the ovarian follicles (See Figure 2).

Figure 2.  Reproduction:  The Ovarian Follicle and the Cycles of Menstruation.  With the monthly cycle, the ovarian follicle prepares an oocyte for maturation and release to the Fallopian tube, with the possibility of fertilization and reproduction. 

There are three types of cells in the human ovary:  the oocyte or mature egg, the granulosa cells, and the external thecal layers.  The follicle houses the oocyte that is maturing to the time of release.  The granulosa cells are in the follicle, and they surround the oocyte.

Hormone production dictates what happens to the follicle. When testosterone increases, the number of granulosa cells decrease.  When gonadotropins (i.e., protein hormones produced by the anterior pituitary gland) increase, the granulosa cells increase in number, not size.  Pituitary gonadotropins include:  follicle-stimulating hormone (FSH) and lutenizing hormone (LH).  FSH tells the granulosa cells to make LH receptors on the cell surface so that when LH is produced and binds to the receptors, the end of the cycle proliferation occurs.  This makes the period stop (see Figure 3).

Figure 3.  Endocrine:  The Ovarian Follicle and Hormone Production.  The human ovarian follicle produces estrogen and progesterone during the Follicular Phase and Luteal Phase, respectfully.  At the time of the early menstrual period, estrogen dominates.  Once the egg is released and there is no fertilization, progesterone dominates.

Another human gonadotropin is produced by the placenta, and this is known as human chorionic gonadotropin (hCG).  The hCG is the hormone test for pregnancy that is commonly used on pregnancy strips.  If hCG is present, placenta is making it.  As the placenta increases in size during the early stages of pregnancy, the hCG also increases in number.  During pregnancy, the placenta also produces estrogen.

During the nonpregnancy state, the human female ovaries produce estrogen, progesterone, and testosterone.  Granulosa cells in the ovarian follicles and the surrounding corpora lutea make estrogen.  Other organ cells participate in estrogen production, but to a lessor extent:  the fat or adipose, liver, breasts, and the adrenal gland.  Postmenopausal estrogen production can still occurs from these extra-ovarian sources, but a woman's individual blood levels must be measured to know what phase her ovaries are in.  In the nonpregnant female, the highest levels of estrogen occur just prior to ovulation, near the end of the Follicular Phase (see Figure 3). 

Figure 4. The metabolism of cholesterol.  A variety of biochemical reactions exist whereby cholesterol is metabolized to progesterone, then on to dehydroepiandrosterone, testosterone, dihydrotestosterone, or estradiol.  Cholesterol is not all bad, and our bodies must produce cholesterol not just in order to procreate, but to develop neurologically. Cholesterol is important to the structure of cells, as well as being a precursor of oxysterols, bile acids, and steroid hormones.  

Cholesterol is the "Mother Molecule" of androgen and estrogen steroids (See Figure 4). Actually, you may be surprised to learn that the cholesterol molecule is a major part of the human brain, and there is no organ in the human body that contains more cholesterol than the human brain (Orth, 2012).  In fact, about 20% of the body’s cholesterol is contained in the brain.  The brain does not have the same metabolic pathway as other organs, and the brain is responsible for what is called de novo synthesis of cholesterol.  This means that the brain makes it freshly. It was Couerbe who, in 1836, described the cholesterol molecule as being “un element principal”, meaning ‘a key element’ in the central nervous system (Couerbe, 1834).

It is important to note that the ovary is uniquely tied into the hormones that they produce.  The ovaries are an organ, and they synthesize and coordinate the lifecycle of a girl and a woman. In old age, the same ovaries dictate how menopause is approached.  

If a woman undergoes a hysterectomy and the surgeon also removes the ovaries, this is 'surgical menopause'. A woman undergoing a hysterectomy gets a 'crash course' in menopause if the ovaries are removed, and she should be offered a discussion of whether or not she should be placed on hormone replacement therapy (HRT).  Backing up for a moment, wait just one moment.  Actually, we must first question whether the ovaries should be removed at all.  Stay tuned for the next article, which will address this issue.

References:

Couerbe JP. Du cerveau, considere sous le point du vue chimique et physiologique. Annales De Chimie Ed De Physique. 1834;56:160-193.

Orth M., and Bellosta S.  Cholesterol: its regulation and role in central nervous system disorders.  Cholesterol, 2012;2012:292598, doi:10.1155/2012/292598. Epub 2012 Oct 17.  http://www.ncbi.nlm.nih.gov/pubmed/23119149

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Additional Articles by Dr. Margaret Aranda

Menopause and Painful Intercourse

The Cochran Report

What Aristotle Thought of Menstruation

From Menarche through Menopause

The History of Menopause

The Different Types of Hysterectomies
Low Sexual Desire: Is It HSDD?

Surgical Menopause and Testosterone Therapy

Bears Can Smell the Menstruation: Or Can They?

The Ovaries: Reproduction and Endocrine Function

The History of Menopause

by Dr. Margaret Aranda

On his Treatise on the History of Animals, Aristotle wrote that menopause occurred in

the fortieth year, but some childbearing up to the fifties was not uncommon.  There is a paucity of writings on menopause in the Greek literature, perhaps because fewer women lived to be of a postmenopausal age. 

The ancient Greeks attributed an “imbalance of humors” to various conditions. Today, we would call it an “imbalance of hormones”.  One of those conditions was the state of infertility due to an inability of an aging woman to have a baby.

The international, social, and biological deficiency state of “imbalance of humors” placed a certain taboo on women worldwide.  Women sought to restore the imbalance, and some of their means were bold.  They placed leeches on their legs, so that the blood-sucking bugs would get rid of the excess blood and create balance. In India, testicular juice was a remedy.  In North America and China, wild yam was used.  There are other extreme measures that women undertook to try to either bring back their periods or alleviate symptoms (see Table).  But these experiments of concoctions proved useful when in the 1950's, the root of the wild yam was harvested for its diosgenin, which is a phytoestrogen. A phytoestrogen is a plant with a hormone that is structurally similar to estrogen.  In the 1960's, based on this chemical conversion of a phytoestrogen to an estrogen, this is how the first birth control was originally formulated.

Early Treatments of Menopause	Time Period	Reference
Can be treated with black cohosh, (Cimifuga racemosa), a natural precursor to estrogen	1700’s	eHow 2012
Can be treated with wild yam, Dioscoria villosa	1800’s	Buchanan 2012
Can be treated with testicular juice	1930’s	Singh et al, 2002
Can be treated with crushed ovaries of animals	1930’s	Singh et al, 2002
Devil had a covenant with the woman	Old pagan and religious belief	Body Logic, 2012
‘Usual mixture’ before meals: carbonated soda, opium, vaginal injections of lead acetate, morphine hydrochlorate, distilled water, chloric ether	1855	Foxcroft 2009
Ovarian extracts used to relieve vasomotor symptoms	1897	Speroff, 1999
Herbals, belladonna, cannabis, or opium	1899	Merck
“Ovarlin” flavored powder, dessicated and pulverized cow ovaries	1899	Merck
Women were insane, giving ‘insane interpretations’ of their symptoms.	1903	Savage 1903

 Table.  Descriptions of the early beliefs of menopause through time.  Menopause carries with it a vivid history of remedies to alleviate the 'insanity' of it all.  Today, some hold that hormone imbalance is best treated with bioidentical hormone replacement therapy.

The Ancient Egyptians are credited with the concoction of elixirs that were used for anti-aging purposes (Utian, WH.,  2008).

Trotula of Salerno, who may have been a female physician, wrote in the 13^th Century writing of women in medieval Europe, The Diseases of Women:

 “Since in women not so much heat abounds that is suffices to use up the moistures which daily collect in them, their weakness cannot endure so much exertion as to be able to put forth that moisture to the outside air as in the case of men.

Nature herself, on account of this deficiency, has assigned for them a special purgation namely the menses, commonly called flowers.  Now a purgation of this sort usually befalls women about the 13^th or 14^th year or a little later according to whether heat or cold abounds in them more.  It lasts up to about the 50^th year if she is lean; sometimes up to the 60^th or 65^th year if she is moist; in the moderately fat up to about the 45^th.” 

In 1821, the term ‘menopause’ was coined by Dr. Charles Négrier (1792 – 1862).  It is derived from the Greek; month is ‘men’, and pause is ‘pausis’. 

In the 1800’s, there was much medical interest in menopause, but not the way that you would think.  The average of menopause in England was 45. Consider that you went into menopause in the 1800’s, complaining of depression, hot flashes, and irregular periods.  Doctors were quick to diagnoses these women with “hysteria”, a major term that literally referred to the uterus in Latin.  The Greek 'hysterus' means ‘womb’, and thus the uterus literally caused ‘hysteria’. The uterus was thought to be the organ responsible for physical problems that led to neuroses.

During this time period, it was not uncommon for wives and daughters to be committed to an insane asylum for reasons of “lunacy”.  Women were even “put away” for gong through menopause.  Husbands would put them away, divorce them, then marry a much younger woman.  No one was allowed to visit the woman in the insane asylum, and they were locked up until they died.  Many times, the husbands would simply say that the woman had died.  Women in this situation were subjected to conditions of poor heating, substandard food, unsanitary and unclean conditions, and communicable diseases spread widely in this environment, which sometimes was adjacent to or part of a prison system (Sansone 2012).

In the 1850’s, Edward Tilt, MD determined that “the keystone of mental pathology” was the uterus.  The Greek hysterus means ‘womb’, and thus the uterus caused ‘hysteria’. 

By 1870, the surgical procedure of hysterectomy was perfected as a quick method to deal with menopausal complaints.  Surgeons took out not only the uterus, but also the ovaries and the cervix.  

It seems that the hysterectomy is still an ultimate alternative to menopause.  Is this a good thing?  In a 2004 study, it was found that Counseling and a Second Opinion physician determined that 98% of hysterectomies were not needed.  Couple that with a 2010 study that estimated that about 500,000 hysterectomies are performed per year in the USA, such that 40% of all women over age 45 do not have a uterus.  How many of these women are offered or are placed on hormone replacement therapy?  

Should postmenopausal women, including those with Surgical Menopause, take hormones?  For many practicing physicians, this is no longer a professional 'debate', it is a public debate that began with the Women's Health Initiative in 1992.   Today, the issues are clear, as the treatment is individualized.  Stay tuned for more.

As 2013 nears, it is important to understand that menopause is still a taboo subject for many women, in many cultures, and throughout the world.  Women are embarrassed to talk about it, and some clam up when the doctor starts asking questions.  Only after effective rapport is established will some women discuss the subject so that symptoms, time increments, and a proper Medical History can be reported.  Women need to speak freely about the matter, so that the medical field can determine the problem, and work towards a solution for each individual woman.  What is it all about?  Quality of life.  It's a Quality of Life issue.

References:

Body Logic MD. The History of Menopause, 2012. http://www.bodylogicmd.com/hormone-articles/the-history-of-menopause

Buchanan, Paul A.  Wild yam restores sex drive during menopause.  Ezine Articles, 2012. http://ezinearticles.com/?Wild-Yam-Restores-Sex-Drive-During-Menopause&id=7099288

eHow.  How to naturally treat hot flashes and menopausal symptoms, 2012. http://ezinearticles.com/?Wild-Yam-Restores-Sex-Drive-During-Menopause&id=7099288

Foxcroft, L. The mad, mad menopause: Louise Foxcroft charts its fascinating, and sometimes gruesome, history.  April 9, 2009.  http://www.dailymail.co.uk/femail/article-1168710/The-mad-mad-menopause-LOUISE-FOXCROFT-charts-fascinating-gruesome-history-.html#comments

Merck Manual: Diagnosis & Therapy.  New York:  Merck and Co., 1899.

Savage George.  A Lecture on the mental disorders of the climacteric.  The Lancet, 1903.

Singh A., et al.  A historical perspective on menopause and menopausal age.  Bull Indian Inst Hist Med Hyderabad 2002 Jul-Dec; 32(2):121-35.

Speroff L.  Clinical Gynecologic endocrinology and infertility.  6^th Edition. Baltimore, MD: Williams and Wilkins; 1999.

Utian WH, et al.  Effect of raloxifine on quality of life: a prospective study using the Utian Quality of Life (UQOL) scale.  Menopause 2004 Jay-Jun:11(3):275-80.

http://www.ncbi.nlm.nih.gov/pubmed/15167306