Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

A journey through two lumens!

Abstract

This account describes studies from the Institute of Medical Physiology in the University of Copenhagen, starting in the mid 1970's, which included some of the earliest European laboratory investigations on human female genital function. The measurements involved vaginal pH, pO2, blood flow, motility, fluid and its ionic concentrations, amino-acid concentrations and electrical activity (transvaginal potential difference) usually in both the basal and sexual aroused states. The blood flow monitoring pioneered the use of the heated oxygen electrode. Other studies examined the effects of arousal to orgasm on cervical secretion, on the heart rate as an objective indicator of orgasmic excitement and investigated the actions of TRH and the cholinergic antagonist atropine on a number of vaginal parameters. The work was part of the scientific watershed that divided the previous descriptive era of human genital mechanisms from the now prevalent quantitative assessments.

Main

Three apothegms that influenced my research philosophy

  1. 1)

    The devil is in the detail.

  2. 2)

    To see what everyone else has seen but to think what no one else has thought.

  3. 3)

    A lawyer's brief is simply to gather all the evidence supporting his case, while a scientist's brief is to gather all the evidence for and against his case and come to a conclusion.

There was a book published in 19971 titled ‘How I got into sex’ with a subtitle of ‘Personal stories of leading researchers, sex therapists, educators, prostitutes, sex toy designers, sex surrogates, transsexuals, criminologists, clergy and more….’ I certainly wasn't asked to contribute, and if my memory serves me right no other European was either, but perhaps it was not too bad an omission looking at the categories in the subtitle! The editor invited me to write an account of my early involvement in the now burgeoning study of the physiology of human sexuality, especially that of the female.

First encounters with academic sex

The very first involvement with academic sex began with having to teach medical students reproduction, but let us start at the true beginning. My scientific training commenced at Liverpool University, where I read for Bachelor of Science degrees in general science and then in Honours Physiology in the laboratory that Sherrington used. The Head of the Physiology Department, Professor Rod Gregory FRS, who was isolating and purifying gastrin (the major gastric hormone that activates acid secretion), invited me in 1957 to accept a University research fellowship to isolate and purify secretin (discovered by Bayliss and Starling, the first blood-borne agent to be named a ‘hormone’ and controls fluid and ion secretion by the exocrine pancreas).This embarked me on my life-long career as an experimental gastroenterologist. Unfortunately, the purification turned out to be too mammoth a task to undertake with the techniques then available. Later, in Uvnas's laboratory in Sweden, even with the newer separation techniques available, thousands of hog small intestines had to be processed to obtain finally but 1 mg of the substance, a highly basic polypeptide. However, the experimental grounding that I obtained undertaking this research for an MSc led me to my first academic position as a research assistant in 1959 in the Department of Physiology at the University of Sheffield, then under the Headship of Professor David Smyth, FRS. Little did I realise that I would stay there for over 40 years. This was probably the first, and only, time that sex looked kindly on my career development as the position became vacant only because a pregnancy caused one of the female staff members to leave! My new field of research was investigating the control of intestinal absorption (and later secretion) by hormones and diet. It was my first encounter with a lumen—the intestinal one. The department had an international reputation for experimental studies on small intestinal function and was the birthplace of the everted small intestinal sac, a remarkably simple preparation where the isolated small intestine was everted and could be tied off into small sacs that actively transferred solutes and fluid from outside the sac into its serosal compartment. The eversion allowed the tissue to be kept oxygenated and alive by being incubated in oxygen-gassed buffer and this made possible the discovery of the absorption by active transport of ions, amino acids, sugars, fatty acids, vitamins, etc. by the enterocytes.2 Studying the physiology of sex was very far from my thoughts during this period. However, when a senior academic left to take up a chair in physiology someone had to take up the teaching of reproduction to the medical and science undergraduates and I volunteered. I was given a free reign, so decided that the medical course would have at least one lecture on the physiology of human sexual arousal and coitus— a near unheard of feature in UK medical schools at that time. No physiology textbook of the period even mentioned the mechanisms of penile erection, ejaculation or vaginal lubrication. There was little scientific literature available. Dickinson's3 Atlas of Human Sex Anatomy (2nd edn) published in 1949 and the descriptive Chapters 14 and 15 (Anatomy and Physiology of Sexual Response and Orgasm, respectively) in Kinsey et als' 4 Sexual Behaviour in the Human Female (1953) were useful, but the publication by Masters and Johnson5 of the Human Sexual Response in 1966 heralded a new dawn. The previous years of repression can hardly be believed in today's world: Chapter 1 of Dickinson's atlas of explicit drawings of human genitals and coitus has a paragraph (p. 5) about the size of the volume that was kept to 8.5×11 in because, I quote, the ‘controlling reason … is that the book may be conveniently locked up in the stock vertical file until such time as everyday medical data like these are commonplace and as clear of reproach and as clean of reproach as any other anatomical figures'! I remember my first reading of the fascinating but turgidly written Human Sexual Response by Masters and Johnson5 and thinking –‘Oh! dear, it's a real pity that they didn't have an experimental physiologist as a team member, look at all the measurements they could have done’. While preparing and giving the lectures I realised the obvious lack of basic information about human genital function and coitus. Statements in Masters and Johnson's book like ‘vaginal physiology has been, and still remains, an essentially unexplored field’ (p 80) highlighted our ignorance.

The early vaginal/endometrial studies

As I was studying the transfer of fluid, ions and solutes across the everted intestines by chemical and electrical measurements, I began to wonder whether the epithelium lining the vagina and the uterus (endometrium) also transferred ions and fluid and by the former, generated electrical activity that could be used as a simple, objective measure of one aspect of the organ's function. Since the vaginal epithelium was a multicell thick tissue, it would need to be dissected out from a rat as an intact tube, and turned inside out to make a sac. Its ability to transfer in vitro ions from lumen to serosa and vice versa was recorded by measuring the electrical potential difference across the preparation when incubated in an oxygen-gassed buffer. Luckily, it worked the very first time I tried it.6 Academic staff members were assigned science students reading for a physiology degree who worked with them on a research project. With Janet Camfield, my undergraduate for 1966 who I trained in the dissection, we obtained enough data to publish the first paper on the first viable in vitro vaginal preparation cheekily entitled ‘The isolated everted vagina—a preparation for studying vaginal bioelectric activity in vitro’.7 My second encounter with a lumen—that of the reproductive tract—had begun. Creating an in vitro uterine endometrial preparation was a little more tricky as the tissue was much more fragile.8 It was around this time that I realised that my background and research experience gave me an advantage over nonphysiologists in the sexual/reproductive field who were unaware of, or misinterpreted, basic biological mechanisms.9 To my surprise even the hallowed Masters and Johnson5 could go astray: they stated, ‘The fact that the vaginal mucosa is a permeable two-way membrane emphasises the difficulty in establishing and maintaining a stable environment’ (p 89). My involvement with the ins and outs of ions and fluid across the intestine made it obvious that a ‘stable (vaginal) lumenal environment’ could actually only be achieved if there was a permeable two-way flux! Any change in the lumen would quickly be equilibrated by passive movements into or out of the bulk phase fluid especially in relation to the electrical potential across the vaginal wall in the case of charged ions. Years later, I returned to the study of the electrical activity generated across the vagina/cervix/uterus using both in vivo and in vitro preparations of the human female10 and from rats. I was dissatisfied with the subjective, pseudoquantitative scoring of classical toxicology that was used to assess gross histological damage to the vagina caused by the insertion of known and putative spermicides/virucides. I thought that measuring the activity of the vaginal epithelial cells to transfer ions across the wall to create an electrical potential difference and current would give an objective quantitative measure of their function, and any agents that caused membrane or cellular damage would be easily and rapidly identified and assessed. These studies culminated in a number of publications on this theme.11,12,13,14 The most recent with human vaginal (ectocervical) tissue incubated in vitro as a sheet15 showed that the cells could actively transfer Na+ ions from the lumen back into the blood, and it was mainly this that generated the potential difference across the human vagina making the lumen negative to the blood by up to 30–40 mV.10 It is also obvious that this reabsorption of Na+ by the vaginal cells is the osmotic cause of the reabsorption in the resolution phase of the increased vaginal ‘lubricating’ fluid, created during sexual excitement, restoring the vagina to the ‘just moist’ resting condition. A recent paper16 using a near-identical preparation of the human vagina confirmed the viability of the tissue in vitro by monitoring its electrical activity, but made no use of it as a preparation to further the study of vaginal function.

The first Danish visit

I had been publishing my experimental studies on the influence of dietary intake and hormones on intestinal function (for which I obtained my PhD as a staff candidate in 1964) concomitant with my few early papers on vaginal and uterine endometrial function. I began to attend and read papers at international conferences. At one of these in 1975, I met Eric Skadhauge, a Danish research academic but also involved in teaching physiology to medical students. He invited me to Copenhagen to lecture the Danish Biological Society on diet and intestinal transport function. We talked about teaching reproduction. At that time the medical school in Copenhagen, in the then new Panum building, had a pioneering course on human sexuality for their medical students organised by Gorm Wagner. Because of my own teaching commitment to the medical students, Eric suggested that I write to Gorm to audit the course during my planned lecture visit. I wrote and duly got a reply from Gorm accepting me on the course and, enclosed with the week's timetable, a synopsis of his film ‘Sexual arousal of the human female in the laboratory’. It bowled me over. Here was somebody in Europe undertaking observations like Masters and Johnson who apparently had access to subjects who sexually aroused themselves for scientific study. I immediately wrote back (no e-mails in those days!) with details of the studies I had published on the vagina and uterus and wondered if it would be possible to undertake a few simple experiments measuring vaginal potential difference, fluid production and its ionic concentration in human subjects during sexual arousal to characterise possible mechanisms of its production. The reply came back ‘Sure, let's have a try.’ The visit in January 1976 was a great success. Gorm met me at the airport and we became instant friends. At the weekend, we undertook a few pilot experiments in Gorm's laboratory in the old Rockefeller physiology building, collecting vaginal fluid on weighed strips of filter paper during control, basal conditions and during sexual arousal, sometimes to orgasm. The results were so promising that we decided to cooperate on a regular basis, with me coming over to Copenhagen in the academic holidays and staying in a guest room in the roof of the Rockefeller building (in fact, we are still working together on a research project in 2002!). In the long summer vacations, my wife and our two young sons came over and all of us stayed in a University flat provided for foreign research workers. Later, the University converted an old nurse's home into a guesthouse for visiting foreign research workers. To this day, I applaud the academic authorities of the University of Copenhagen for their great foresight in creating and funding highly subsidised accommodation for foreign research workers to stay and work with the faculty at their University. It allowed studies to be undertaken for low accommodation costs and fostered international academic cooperation. It is a feature that is still in operation today.

The Danish research period

The research was very productive. Over the years from 1976, we published a number of papers with the help of our respective laboratory technicians Birdie Knudsen (Copenhagen University) and Andy Parker (Sheffield University). There were only a handful of personnel and laboratories undertaking research and publishing on human female sexual arousal in the late 1970s; most were males in the United States—Jim Geer,17 Peter Hoon,18 Henson and Rubin19 and Julia Heiman20—the lone woman performing such studies in the USA. Only two groups were active in the UK, Cyril Fox with his unique ‘family bedroom’ studies21 and the single photoplethysmographic study by Gillan and Brindley.22 Later, other women entered the field—Ellen Laan in Amsterdam, and Cindy Meston and Eileen Palace in the States.

The academic world of physiology in the UK was hugely uninterested in the work; some were outright antagonistic. Looking back, my decision to research human sexual arousal is what academics now call a career-limiting move (CLM)! There was little doubt that the laboratory studies on sexual arousal and especially orgasm were looked on by some senior members of the UK academic community (even physiologists) with some disapproval, and I was even told that such studies did not collect many ‘brownie points’ when it came to the evaluation of one's research output. The unique course of explicit lectures that I created in the department at Sheffield for our final year honours physiologists dealing with the mechanisms of human sexual arousal entitled ‘The physiology of human sexuality’, unsurprisingly a very popular course, was criticised by one external examiner because he thought, mistakenly, that the study of ‘human sexuality’ was unscientific (despite the fact that I was undertaking basic physiological measurements of the activity) and that my students' reading list referred to too many of my own papers! I recall giving an oral communication on female sexual arousal at a Physiological Society meeting in the UK, where the first question after my delivery was not related to the science I presented but simply ‘How much did you pay the female subjects?’ with its obvious implication that the subjects of the study were prostitutes. As always funding for travel, maintenance, consumables, etc. was a problem, but fortunately there were supportive people and agencies and we managed to get by with a hand-to-mouth existence with small grants from a variety of sources (International Planned Parenthood Federation, the British Council, the Wellcome Foundation, the Royal Society, The Foundation for the Scientific Study of Sex, the University of Copenhagen and Sheffield's medical research funds, a variety of local Danish funds and later a number of pharmaceutical company grants). Since Gorm found money to pay someone to undertake my teaching obligations, I was able to take a 6-month sabbatical in Copenhagen in 1986, coming back to visit my long-suffering wife and young family for the odd weekend! It was a little time after the appearance of Toxic Shock Syndrome when some 30 women had died in the States because of toxic shock induced probably by the combination of a new tampon and a bacterial infection that created a deadly toxin. Studies with tampons showed that when they were inserted into the vagina, because of the air trapped between the fibres they raised the pO2 of the normally hypoxic lumen quite dramatically to atmospheric levels, creating conditions for the growth of Staphylococcus aureus and the production of a protein toxin.23 Later studies showed that even inserting a solid rubber Dutch cap (diaphragm) into the vagina dramatically elevated its lumenal oxygen.24 Prior to these studies, the concept that the insertion of vaginal devices could dramatically alter its gaseous environment and thus have potential effects on the bacteria was not considered.

Animal models for vaginal studies

We were working on the effects of VIP on vaginal blood flow and wanted an animal model to undertake invasive experiments. The choice of an animal vagina to match exactly that of the human is difficult. That of the rabbit unfortunately consists of a two-thirds caudal (upper) section lined with columnar epithelium (like the cervix) and a one-third distal (lower) part with squamous epithelium similar to that of the human, making it imperative that the upper section is tied off. Unlike the human, the vaginas of small rodents (rats, hamsters, guinea pigs) undergo enormous histological changes during their normal 4–5 day oestrus cycles, from a 2-cell-thick, cuboidal epithelium to a squamous epithelieum (with cornification) some 10–20 cells thick. The properties of the vagina depend greatly on the stage of the oestrus cycle.11,25 The dog is not only a very expensive experimental animal in Europe but its vagina is very S-shaped under the pubic symphysis, making insertion of our large measuring devices difficult. We finally settled on the sheep. It was cheap and easily available. While the normal pH of its vagina is about 7, it becomes more like the acidified pH 4–5 of the human vagina when heavily oestrogenised. We used it to assess the vasodilator properties of intravenous and locally applied VIP and evaluated the effects of TRH on vaginal blood flow.26 TRH, a simple tripeptide, is fascinating because it appears to be the only compound that when injected into conscious women creates a feeling of genital warmth probably because of a transient increase in genital blood flow and a low level of sexual arousal. It appears to have no action on male genitals. Since our study, no further investigation of this phenomenon has been published. We were the first European laboratory to begin to quantitate physiological aspects of vaginal function in the resting and sexually aroused states. We summarised the early studies in a chapter in the book The Human Vagina published in 1978.27

Our successes?

(i) We showed that the basal vaginal fluid had a low Na+ and a very high K+ compared to plasma, and that this remained so throughout both phases of the menstrual cycle and therefore was uninfluenced by oestrogen and progesterone.28 By placing sacs of visking tubing filled with autologous serum (obtained from the subject) into the subject's vagina for a few hours, we showed that the ionic changes in the serum were compatible with vaginal epithelial mechanisms for the secretion of K+ into the vaginal fluid and for an absorption of Na+ and Cl out of the fluid.29 During sexual arousal, the ‘fluid’ that moved into the vagina had a greatly enhanced NaCl concentration, supporting the hypothesis that it was a (neurogenic) transudate coming from the plasma.29,30 You have to realise that at the time medical physiology knew the ionic concentrations of practically every human body fluid (even that of the endolymph inside the cochlea!) but showed complete indifference as to what the concentrations of Na+, K+, Cl, and Ca2+ were in human vaginal fluid! Indeed, one of my critics said, ‘Why on earth do you want to know the ion concentrations of the vaginal fluids, of what possible purpose can it be useful for?’ Apart from the fact that it is the first genital fluid that the spermatozoa are ejaculated into and its ions may well have important reproductive influences (see Wagner and Levin28 for a discussion), two studies have utilised our data to create an artificial vaginal fluid for use in work on bacterial growth in vaginal fluids and the role of the ions on vaginal bacteriocides and spermicides.31,32 We also showed that the basal vaginal fluid contained remarkably high values of a number of amino acids.33 The five highest levels were those of aspartic acid (71 times that of plasma), taurine (48 times that of plasma), ethanolamine (29 times that of plasma), glutamic acid (12 times) and methionine (10 times plasma). The role(s) of these high concentrations have not been studied, but one possibility is that as taurine is known to affect (stabilise) animal sperm membranes,34,35 it could have similar actions in the human female.

(ii) We pioneered the use of the heated oxygen electrode in human vaginal studies.36 Unlike the photoplethysmograph, it could be used to monitor vaginal function throughout sexual arousal to and after orgasm. It was originally produced by Radiometer, Copenhagen, for hospital intensive-care units. The firm was extremely generous in helping us in our studies. We held it onto the vaginal wall by inserting it into a suction capsule (based on the design of the suction capsules used to collect parotid saliva in humans) and measured the oxygen tension of the vaginal surface fluid both in the basal and in the sexually aroused to orgasm conditions.37 In the basal or nonsexually aroused state, the vaginal surface oxygen level was very low, practically anaerobic (pO2=9±11 mmHg, mean±s.d.). Sexual arousal caused a rapid increase in the pO2 to 50 mmHg or more while orgasm brought about its dissipation. The low basal vaginal pO2 was in keeping with the normal flora of Lactobacilli (Doderlein's bacillus), a facultative anaerobe presumed to be a major manufacturing source of the acidity of vaginal fluid. The danger of publishing such early studies way ahead of general academic interest is that later research workers (and the referees who review the work) do not bother to read any literature more than 5 and certainly 10 years back! You then are chagrined to see a publication measuring the oxygen tension of the vaginal wall claiming it to be a new way to assess sexual arousal in the human female without any acknowledgement of the fact that it was repeating work accomplished 24 years back (see Levin and Wagner38 for a comment). As few researchers like to hear ‘We did that twenty odd years ago’ said about their work, a good literature search before embarking on a research project is an essential prophylactic (the devil is in the detail).

(iii) We utilised the built-in ability of the Radiometer oxygen electrode to measure indirectly the blood flow underneath it by monitoring the heat loss of the electrode in terms of the electrical power in milliwatts needed to maintain its original set temperature, usually a few degrees above blood temperature.36 Comparing the AC-signals obtained by vaginal photoplethysmography with those obtained from the heated oxygen electrode showed that there were real discrepancies immediately after orgasm.39 This created doubts about the usual simple interpretation of the AC signal amplitude as a direct measure of vasodilatation, but the warning was unheeded and still remains so! The AC-signal is so easy to obtain and appears so very simple, but in reality the interpretation of it is much more complicated. A feature ignored is that changes in venous tone may well be a factor in affecting the amplitude of the AC signal;40 an enhanced venous tone creating a reduced venous drainage may well create an artifactually high amplitude giving the appearance of increased arterial blood flow.

(iv) In our laboratory study of orgasm,41 we found that the increase in vaginal blood flow at orgasm was not correlated to the gradings of the orgasm by the subject, or the orgasm latency (time taken to induce the orgasm) or the measured duration of orgasm. The mean duration of orgasm as measured from the subjects' verbal signals of initiation and end was 19.9 s (n=26), but when they were asked to estimate how long the orgasm lasted, this was greatly underestimated being some 12.2 s.

(v) We were the first to show that the subjective intensity of orgasm could be related to an objective physical measure, namely the increase in heart rate during the period just before orgasm;42 the greater the increase, the better the grade of orgasm. The finding was later confirmed.43

(vi) We assessed the secretory function of the cervix during arousal to orgasm by monitoring its surface pH and ionised pCa2+ using pH and pCa2+ electrodes held against the ectocervix and showed that there was little change.44 As far as I know, this is the only study of cervical function during sexual arousal to orgasm where actual measurements have been made.

(vii) We showed that the increase in vaginal blood flow during sexual arousal was unaffected by atropine, a powerful blocker of cholinergic transmission, and it had little or no effect on the induction of orgasm. This was the first experimental evidence indicating that it was highly unlikely that acetylcholine, previously assumed to be the neurotransmitter enhancing vaginal blood flow and the lubricating mechanism of the vagina, was involved.45 A few years later, Riley and Riley46 showed, as expected, that atropine had no effect on vaginal lubrication. Later studies by Gorm with Bent Ottesen and colleagues infusing VIP in conscious human subjects strongly suggested that it could be the transmitter for the increase in vaginal blood flow at arousal and the enhanced production of vaginal fluid.47

(viii) We measured the vaginal pH at six separate surface sites under direct observation during basal conditions and after sexual arousal to orgasm, and found that on some sites there could be a large increase in pH (at least 1 unit) while at others there was very little or even an occasional decrease.48 Masters49 had previously made similar measures, but he placed the electrode blindly into the vagina and did not undertake any statistical analysis of his data. A study using a radiotelemetry pH electrode placed high up in the fornix in just one subject50 did not find any change in pH during coitus to orgasm. As a result of this, they questioned the hypothesis that the lubrication fluid formed on the surface of the vagina at arousal was a transudate of plasma as they assumed that the pH should have become neutralised to pH 7. They overlooked two factors: (i) that the upper part of the vagina is the least responsive to the formation of the transudate and (ii) the pH measuring membrane of the electrode may simply have been on a site that showed little change. This made their challenge of the hypothesis very weak, if not invalid. The heterogeneity of the pH response to sexual arousal makes the employment of the pH change a poor index of normal vaginal function.

The latter years

After this burst of activity studying various aspects of female sexual arousal in the laboratory by us and other workers in the 1970s and 1980s, research support funds became increasingly difficult to obtain, and a lull or quiet period ensued.51,52 The research ticked over and papers were published, but there was still very little interest/support shown in the study of the physiology of female sexual arousal. The sea change occurred on the serendipitous discovery of the oral treatment for erectile dysfunction—sildenafil and the inhibition of PDE5 creating vasocongestion. Suddenly a simple oral treatment for a major sexual dysfunction appeared that worked in a surprising number of cases and swept away the hallowed concepts of long-term ‘word treatments’. Erectile dysfunction appeared vanquished and the pharmaceutical industry's whetted appetite for new sexual fields to conquer grew. The answer was obvious—if it could be accomplished for men then why not for women, because there was evidence of a growing awareness of sexual dysfunction in women53 that needed to be addressed. The focus of attention was turned to women and magically pharmaceutical companies, old and new, started to look at female sexual dysfunction in a new light—if a pill could be found for men surely it could also be created for women. With this came the realisation that female sexual physiology had been practically ignored, certainly grossly underfunded and that a concertive effort was needed to stimulate the field. The European Society for the Study of Impotence created a section for women's sexual function and dysfunction and its newsletter now has a regular topical section on research themes on female sexual function. I gave the first female-based lecture at their Second Annual Conference in Madrid in 1997 entitled ‘Sex and the human female reproductive tract—what really happens during and after coitus’. My opening comment was that they had all come to learn how to create an erection and here I was going to tell them in the next 50 min how to lose it—with pleasure! The International Society for Impotence Research has now changed its title to International Society for Sexual and Impotence Research in order to cover female studies and its journal title is restyled to ‘The International Journal of Impotence Research—Journal of Sexual Medicine’ to broaden its field to include female studies. Irwin Goldstein, with his inimitable energy and drive, created the Female Sexual Function Forums in Boston, bringing hundreds of workers in the field together to meet and discuss about female sexual function and dysfunction. This has finally culminated in the creation of a new society—the International Society for the Study of Women's Sexual Health (ISSWSH), whose first highly successful meeting was in Vancouver in October 2002. Zucker54 has described how the handful of journals that dealt with human sexuality in the 1970s has now grown to some 76 titles.

Now retired from my position after 41 years in the joint academic harness of departmental research, teaching and administration, the restraints on time have gone. I can prosecute research and write critical reviews on the topics of my choice (see Levin55,56) without worrying about whether they fit a department's, university's or government's mission statement! Recently, I realised that I could offer an explanation for the enigma of vaginal tenting, the elevation of the cervix away from the posterior vaginal wall and the ballooning of the distal vagina described by Masters and Johnson5 some 37 years ago. Unlike previous explanations that always claimed that changes in the female genital tract brought about by sexual arousal facilitated sperm transport, in my explanation, it occurs to delay sperm transport allowing the crucial liquefaction of the semen and capacitation of the sperm to occur.57 Inadequate tenting because of poor arousal may be a cause of infertility because it allows too rapid transport of incompetent sperm. Thus, even after 37 years of the description of a basic genital phenomenon have passed, one can still interpret its fundamental role in human sexual arousal and fertility. That is the excitement of science—it is never static (see research apothegm number 2).

Last words

In a perceptive article on scientists involved in sex research, Weinrich58 grouped them into three ideal types. In his definitions, ‘Pioneers are the first to come up with a new idea that eventually replaces the older one, they are the revolutionaries; Provers are the first to prove to sceptics that the idea is true, they are the implementers of the revolution; Critics are the last to hold onto the previous older ideas, they are the preservers of the revolution.’ Scientists need to perform in all three modes. In my career, I have had my share of pioneering, proving and criticising but most of all it has been a wonderful and privileged experience. To the subjects who volunteered and the colleagues I cooperated with— and still do—my heartfelt gratitude.

References

  1. 1

    Bullough B, Bullough VL, Fithian MA, Klein RS . How I Got Into Sex. Prometheus Book: Amherst, New York, 1974.

    Google Scholar 

  2. 2

    Levin RJ . Discussion. In: Christie DA, Tansey EM (eds). Wellcome Witnesses to Twentieth Century Medicine, Vol. 8, Intestinal Absorption. The Wellcome Trust: London, 2000, pp 22–26.

    Google Scholar 

  3. 3

    Dickinson RL . Atlas of Human Sex Anatomy, 2nd edn. The Williams & Wilkins Company: Baltimore, 1949.

    Google Scholar 

  4. 4

    Kinsey AC, Pomeroy WB, Martin CE, Gebhard PH . Sexual Behaviour in the Human Female. W.B. Saunders: Philadelphia, 1953, Chapters 14, 15.

    Google Scholar 

  5. 5

    Masters WH, Johnson VE . Human Sexual Response. Little, Brown: Boston, 1966.

    Google Scholar 

  6. 6

    Levin RJ . The effects of hormones and the oestrous cycle on the transvaginal potential difference. J Physiol 1968; 194: 94–95P.

    Google Scholar 

  7. 7

    Levin RJ, Camfield J . The isolated everted vagina—a preparation for studying vaginal bioelectric phenomena in vitro. Life Sci Oxford 1967; 6: 1871–1881.

    CAS  Article  Google Scholar 

  8. 8

    Levin RJ, Edwards FE . The transuterine endometrial potential difference, its variation during the oestrous cycle and its relation to uterine secretion. Life Sci. Oxford 1968; 7: 1019–1036.

    CAS  Article  Google Scholar 

  9. 9

    Levin RJ . A critique on the relevance of membrane potentials to the mechanism of nidation. J Endocrinol 1973; 58: 141–142.

    CAS  Article  Google Scholar 

  10. 10

    Duncan S, Levin RJ . Transuterine, transendocervical and transvaginal potential differences in conscious women measured in situ. J Physiol 1976; 259: 27–28P.

    Article  Google Scholar 

  11. 11

    Levin RJ . Bioelectric activity as a quantifiable index of acute spermicide (nonoxynol-9) action on vaginal epithelial function during the oestrous cycle. Pharmacol Toxicol 1987; 60: 175–178.

    CAS  Article  Google Scholar 

  12. 12

    Levin RJ . Structure/activity relationships of a homologous series of surfactants (nonyl-phenoxypolyethoxyethanol) on rat vaginal bioelectric activity over the oestrous cycle. Pharmacol Toxicol 1988; 62: 131–134.

    CAS  Article  Google Scholar 

  13. 13

    Levin RJ, Parker AJ . Spermicide action on the vagina: effects of a new, non-surfactant spermicide (RS37367) on rat vaginal electrogenic transfer and permeability in vitro. Med Sci Res 1987; 15: 1045–1046.

    CAS  Google Scholar 

  14. 14

    Levin RJ, Parker AJ . Human vaginal (ectocervix) epithelium in vitro—a preparation for assessing the acute actions of spermicides and other agents 1. Nonoxynol-9 and DL-propranolol. Med Sci Res 1988; 16: 695–696.

    CAS  Google Scholar 

  15. 15

    Levin RJ . Actions of spermicidal and viricidal agents on electrogenic transfer across human vaginal epithelium in vitro. Pharmacol Toxicol 1998; 81: 219–225.

    Article  Google Scholar 

  16. 16

    Bechgaard E, Riis KI, Jorgensen L . The development of an Ussing chamber technique for isolated human vaginal mucosa, and the viability of the in vitro system. Int J Pharm 1994; 106: 237–242.

    Article  Google Scholar 

  17. 17

    Geer J, Quartararo JD . Vaginal blood volume responses during masturbation. Arch Sex Behav 1976; 5: 403–413.

    CAS  Article  Google Scholar 

  18. 18

    Hoon P . The assessment of sexual arousal in women. Prog Behav Mod 1979; 7: 1–61.

    Article  Google Scholar 

  19. 19

    Henson DE, Rubin HB . A comparison of two objectives measures of sexual arousal of women. Behav Res Ther 1978; 16: 143–151.

    CAS  Article  Google Scholar 

  20. 20

    Heiman J . Issues in the use of psychophysiology to assess female sexual dysfunction. J Sex Mar Ther 1976; 2: 197–204.

    CAS  Article  Google Scholar 

  21. 21

    Fox CA, Fox BA . Blood pressure and respiratory patterns during human coitus. J Reprod Fertil 1969; 22: 587–590.

    Article  Google Scholar 

  22. 22

    Gillan P, Brindley GS . Vaginal and pelvic floor responses to sexual stimulation. Psychophysiology 1979; 16: 471–481.

    CAS  Article  Google Scholar 

  23. 23

    Wagner G, Bohr L, Wagner P, Petersen LN . Tampon-induced changes in vaginal oxygen and carbon dioxide tensions. Am J Obstet Gynecol 1984; 148: 147–150.

    CAS  Article  Google Scholar 

  24. 24

    Wagner G, Levin RJ, Bohr L . Diaphragm insertion increases human vaginal oxygen tension. Am J Obstet Gynecol 1988; 158: 1040–1043.

    CAS  Article  Google Scholar 

  25. 25

    Edwards F, Levin RJ . The bioelectric parameters of the vagina during the oestrus cycle of the rat. J Physiol 1975; 248: 307–315.

    Article  Google Scholar 

  26. 26

    Levin RJ, Wagner G . TRH and vaginal blood flow—effects in conscious women and anesthetized sheep. J Physiol 1986; 378: 83P.

    Google Scholar 

  27. 27

    Wagner G, Levin RJ . Vaginal fluid. In: Hafez ESE, Evans T (eds). The Human Vagina. North-Holland Publishing Co.: Amsterdam, 1978, pp 121–138.

    Google Scholar 

  28. 28

    Wagner G, Levin RJ . Electrolytes in vaginal fluid during the menstrual cycle of coitaly active and inactive women. J Reprod Fertil 1980; 60: 17–27.

    CAS  Article  Google Scholar 

  29. 29

    Levin RJ, Wagner G . Mechanisms for vaginal ion movement in women. J Physiol 1978; 284: 172–173P.

    Google Scholar 

  30. 30

    Levin RJ, Wagner G . Human vaginal fluid—ionic composition and modification by sexual arousal. J Physiol 1977; 266: 62–63P.

  31. 31

    Geshnizgani AM, Onderdonk AB . Defined medium simulating genital tract secretions for growth of vaginal microflora. J Clin Microbiol 1992; 30: 1323–1326.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. 32

    Owen DH, Katz DF . A vaginal fluid simulant. Contraception 1999; 59: 91–95.

    CAS  Article  Google Scholar 

  33. 33

    Levin RJ, Wagner G . Quantitative analysis of amino acids in human vaginal fluid during the menstrual cycle. J Physiol 1983; 343: 87P.

    Google Scholar 

  34. 34

    Ozasa H, Gould KG . Protective effect of taurine from osmotic stress on chimpanzee spermatozoa. Arch Androl 1982; 9: 121–126.

    CAS  Article  Google Scholar 

  35. 35

    Alvarez JG, Storey BT . Taurine, hypotaurine, epinephrine and albumin inhibit lipid peroxidation in rabbit spermatozoa and protect against loss of motility. Biol Reprod 1983; 29: 548–555.

    CAS  Article  Google Scholar 

  36. 36

    Levin RJ, Wagner G . Haemodynamic changes of the human vagina during sexual arousal assessed by a heated oxygen electrode. J Physiol 1978; 275: 23–24.

    Google Scholar 

  37. 37

    Wagner G, Levin RJ . Oxygen tension of the vaginal surface during sexual stimulation in the human. Fertil Steril 1978; 30: 50–53.

    CAS  Article  Google Scholar 

  38. 38

    Levin RJ, Wagner G . Re-measurement of vaginal and minor labial oxygen tension for the evaluation of female sexual function. J Urol 2001; 166: 2324.

    CAS  Article  Google Scholar 

  39. 39

    Levin RJ, Wagner G, Ottesen B . Simultaneous monitoring of human vaginal haemodynamics by three independent methods during sexual arousal. In: Hoch Z, Lief HI (eds). Sexology. Proceedings of the fifth World Congress Sexology 1981. Excerpta Medica: Amsterdam, 1981, pp 115–120.

    Google Scholar 

  40. 40

    Levin RJ . Assessing human female sexual arousal by vaginal photoplethysmography—a critical examination. Eur J Med Sexology (Sexualities) 1977; 6: 25–31.

    Google Scholar 

  41. 41

    Levin RJ, Wagner G . Orgasm in women in the laboratory —quantitative studies on duration, intensity, latency and vaginal blood flow. Arch Sex Behav 1985; 14: 439–449.

    CAS  Article  Google Scholar 

  42. 42

    Levin RJ, Wagner G . Heart rate change and subjective intensity of orgasm in women. IRCS Med Sci 1985; 13: 885–886.

    Google Scholar 

  43. 43

    Alzate H, Useche B, Vilegas M . Heart rate change as evidence for vaginally elicited orgasm and intensity. Ann Sex Res 1989; 2: 345–357.

    Article  Google Scholar 

  44. 44

    Levin RJ, Wagner G . Ionised calcium concentrations in human cervical fluid in situ before and after sexual arousal. IRCS Med Sci 1985; 13: 406–407.

    CAS  Google Scholar 

  45. 45

    Wagner G, Levin RJ . Effect of atropine and methylatropine on human vaginal blood flow, sexual arousal and climax. Acta Pharmacol Toxicol 1980; 46: 321–325.

    CAS  Article  Google Scholar 

  46. 46

    Riley AJ, Riley EJ . Cholinergic and adrenergic control of human sexual responses. In: Whetley D (ed). Psychopharmacology and Sexual Disorders. Oxford University Press: Oxford, 1983, pp 125–137.

    Google Scholar 

  47. 47

    Ottesen B et al. Vasoactive intestinal polypeptide (VIP) provokes vaginal lubrication in normal women. Peptides 1987; 8: 797–800.

    CAS  Article  Google Scholar 

  48. 48

    Wagner G, Levin RJ . Human vaginal pH and sexual arousal. Fertil Steril 1984; 41: 389–394.

    CAS  Article  Google Scholar 

  49. 49

    Masters WH . The sexual response cycle of the human female: vaginal lubrication. Ann NY Acad Sci 1959; 83: 301–307.

    CAS  Article  Google Scholar 

  50. 50

    Fox CA, Meldrum SJ, Watson BW . Continuous measurement by radiotelemetry of vaginal pH during human coitus. J Reprod Fertil 1973; 33: 69–75.

    CAS  Article  Google Scholar 

  51. 51

    Levin RJ . The mechanisms of human female sexual arousal. Ann Rev Sex Res 1992; 3: 1–48.

    Article  Google Scholar 

  52. 52

    Levin RJ . VIP, vagina, clitoral and periurethral glans—an update on human female genital arousal. Exp Clin Endocrinol 1991; 98: 61–69.

    CAS  Article  Google Scholar 

  53. 53

    Lauman EO, Paik A, Rosen RC . Sexual dysfunction in the United States: prevalence and predictors. J Am Med Assoc 1999; 281: 537–544.

    Article  Google Scholar 

  54. 54

    Zucker KJ . From the Editor's desk; receiving the torch in the era of sexology's renaissance. Arch Sex Behav 2002; 31: 1–6.

    Article  Google Scholar 

  55. 55

    Levin RJ . Sexual desire and the deconstruction and reconstruction of the human female sexual response model of Masters and Johnson. In: Everaerd W, Laan E, Both S (eds). Sexual Appetite, Desire and Motivation: Energetics of the Sexual System. The Royal Netherlands Academy of Arts and Sciences: Amsterdam, 2000, pp 63–93.

    Google Scholar 

  56. 56

    Levin RJ . Do women gain anything from coitus apart from pregnancy? Changes in the human female genital tract activated by coitus. J Sex Marital Ther 2003; 29s: 59–69.

    Article  Google Scholar 

  57. 57

    Levin RJ . The physiology of sexual arousal in the human female: a recreational and procreational synthesis. Arch Sex Behav 2002; 31: 405–411.

    Article  Google Scholar 

  58. 58

    Weinrich JD, Love child: my career as a sexologist pioneer, prover, and critic. In: Bullough et al (eds). How I Got Into Sex. Prometheus Books: Amherst, New York, 1997, pp 459–471.

    Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to R J Levin.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Levin, R. A journey through two lumens!. Int J Impot Res 15, 2–9 (2003). https://doi.org/10.1038/sj.ijir.3900977

Download citation

Further reading

Search

Quick links